Takenori Takahashi

Penicillium marneffei infection diagnosed by polymerase chain reaction from the skin specimen

We describe a case of Penicillium marneffei infection in a patient with AIDS who had skin eruptions disseminated over the entire surface of his skin. We identified P marneffei from the skin biopsy specimen by polymerase chain reaction using a set of primers specific for this pathogen.

Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case–control study

AbstractFilaggrin (FLG) plays an important role in the barrier function of the skin. Several loss-of-function mutations in the FLG gene have been identified in patients with ichthyosis vulgaris, and these null mutations are associated with atopic dermatitis (AD) development. In this study, we examined tag single nucleotide polymorphisms (tSNPs) and null mutations in FLG for possible associations with AD and atopic phenotypes in a Japanese population. Transmission disequilibrium test of 105 AD families showed that the null allele of the S2554X variant of FLG tended to be overtransmitted to AD-affected offspring; however, the P value did not reach statistical significance. In a case–control comparison of 376 AD cases and 923 nonallergic controls, the null allele of S2554X was significantly associated with AD (P = 0.0012), and the association was strengthened in subjects with AD alone (P = 0.000024). We found that 3321delA and S2554X were also associated with elevated levels of immunoglobulin E (IgE). Combined null mutation carriers were observed more in AD patients and in subjects with high IgE than in control subjects. The combined P value for the family and case–control data was significant for the S2554X and combined null mutations. Our data further support the importance of FLG in AD development.

Single nucleotide polymorphism-based genome-wide linkage analysis in Japanese atopic dermatitis families

BackgroundAtopic dermatitis develops as a result of complex interactions between several genetic and environmental factors. To date, 4 genome-wide linkage studies of atopic dermatitis have been performed in Caucasian populations, however, similar studies have not been done in Asian populations. The aim of this study was to identify chromosome regions linked to atopic dermatitis in a Japanese population.MethodsWe used a high-density, single nucleotide polymorphism genotyping assay, the Illumina BeadArray Linkage Mapping Panel (version 4) comprising 5,861 single nucleotide polymorphisms, to perform a genome-wide linkage analysis of 77 Japanese families with 111 affected sib-pairs with atopic dermatitis.ResultsWe found suggestive evidence for linkage with 15q21 (LOD = 2.01, NPL = 2.87, P = .0012) and weak linkage to 1q24 (LOD = 1.26, NPL = 2.44, P = .008).ConclusionWe report the first genome-wide linkage study of atopic dermatitis in an Asian population, and novel loci on chromosomes 15q21 and 1q24 linked to atopic dermatitis. Identification of novel causative genes for atopic dermatitis will advance our understanding of the pathogenesis of atopic dermatitis.

The combination of ubiquitous transcription factors AP-1 and Sp1 directs keratinocyte-specific and differentiation-specific gene expression in vitro

Abstract:  Previous studies of epidermal‐specific gene promoters suggested that a limited set of transcription factors regulate keratinocyte‐specific and differentiation‐specific gene expression in the epidermis. In the present study, we investigated the functional importance of AP‐1‐ and Sp1‐binding elements in the determination of cell type‐specific and differentiation‐specific gene expression by transient transfection into undifferentiated and differentiated keratinocytes as well as into various non‐epidermal cell lines. Synthesized short AP‐1‐ and/or Sp1‐binding elements were inserted into a minimal reporter vector, and the artificial promoter containing both AP‐1 and Sp1 elements showed high levels of transcriptional activity only when transfected into differentiated keratinocytes. Promoters containing either the AP‐1 or the Sp1 motif alone showed little activity in any of the cells examined. We also found that close proximity of the Sp1 and AP‐1 sites is essential for transcriptional activity, suggesting that the physical interaction between Sp1 and AP‐1 factors is important for functional activity. These results clearly demonstrate that the combination of ubiquitously expressed transcription factors AP‐1 and Sp1 confers keratinocyte specificity and differentiation specificity on the gene expression. Our findings also provide a simple model of the mechanisms underlying regulation of cell type‐specific and cell differentiation‐specific gene expression by ubiquitously expressed transcription factors.

The induction of tumor‐specific CD4+ T cells via major histocompatibility complex class II is required to gain optimal anti‐tumor immunity against B16 melanoma cell line in tumor immunotherapy using dendritic cells

Abstract:  We have demonstrated that dendritic cells (DCs) genetically modified to express tumor‐associated antigens (TAAs) with retroviral vectors elicit more potential anti‐tumor effect than those loaded with peptides because they can prime antigen‐specific CD4+ T cells resulting in production of tumor‐specific antibody. In this study, we showed the importance of antigen presentation via a major histocompatibility complex (MHC) class II molecule in cancer immunity against non‐membrane bound TAAs such as the melanoma antigen gp100 by using DCs derived from MHC class II‐deficient mice (C2KO). DCs were prepared by transduction of gp100 cDNA into haematopoietic progenitor cells obtained from C2KO followed by differentiation with cytokines (C2KO‐gp/DCs). When C2KO‐gp/DCs were inoculated into immunocompetent mice, the mice scarcely primed the antigen‐specific Th1 cells and developed fewer CD8 T cells than did those inoculated with transduced DCs prepared from normal mice. The attenuated anti‐tumor effect was also confirmed in a postimmunization setting where, while two of eight control mice eradicated the pre‐existing melanoma cell line B16 (25%), no mice inoculated with C2KO‐gp/DCs did. These results suggested not only the limitation of current protocols using MHC class I‐restricted tumor peptides but also the usefulness of DCs expressing gp100 in vaccine therapy against melanoma.

Tumor lysis syndrome after transcatheter arterial infusion of cisplatin and embolization therapy for liver metastases of melanoma

Background  Tumor lysis syndrome (TLS) is rare in the treatment of solid tumors, but it may occur in myelolymphoproliferative diseases.

Cutaneous carcinosarcoma comprising basal cell carcinoma and CD34+ fibrosarcoma

© 2007 The Authors 757 JEADV 2008, 22, 745–775 Journal compilation

Multiple microvenular hemangiomas in a healthy child.

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Epidermal cell necrosis with direct epidermal infiltration of Epstein-Barr virus (EBV)-encoded small nuclear RNA-positive T lymphocytes in a patient with EBV-associated haemophagocytic syndrome.

with cryoglobulinaemia is effective and safe. There are two known mechanisms by which cryoglobulins can result in disease. The first is by precipitation within the vascular lumen, typically cold induced, with hyaline plug formation and minimal early-phase inflammation. Typical clinical lesions would be minimally inflammatory cutaneous infarction with or without associated livedo reticularis, or noninflammatory retiform purpura. The second mechanism is that of immune complex vasculitis. As nearly all type II (monoclonal component, usually IgM; polyclonal component, usually IgG) and III (one or more polyclonal components) cryoglobulins are immune complexes, they should all be capable of inducing an immune complex vasculitis, although many do not. Histological examination of an early purpuric lesion in our patient clearly showed cryoglobulin thrombus formation within the dermal vessels. The scarcity of polymorphonuclear leucocytes and leucocytoclasia among the histopathological findings argue against a primary vasculitic process. On the other hand, histology of a recurrent painful nodule revealed leucocytoclastic vasculitis. This is considered to be a secondary event rather than the primary event involved in the pathogenesis. These features favour a thrombo-occlusive vasculopathy rather than a vasculitis per se. Cryoglobulins have been implicated in intravascular thrombotic processes with secondary leucocytoclastic vasculitis that can result in skin infarction and necrosis. In conclusion, we believe that lipo-PGE1 treatment combined with low-dose oral corticosteroid effectively eliminated cryoglobulins and improved leg purpura and skin ulcers in our patient with livedoid vasculitis. Further studies will be needed to clarify the clinical application of lipo-PGE1, but we expect that lipo-PGE1 treatment will be effective among selected patients with cryoglobulinaemic vasculitis.

A case of syringoid eccrine carcinoma with circumscribed abundant stroma

Editor Syringoid eccrine carcinoma is a rare tumour that shows a slow growth and has often been present for many years, sometimes decades, before diagnosis. 1 Histologically, the tumour is characterized by syringoma-like tadpole morphology composed of basaloid cells with ductular differentiation. However, the tumour cells are deeply invasive and often extend to subcutaneous tissue, which distinguishes this malignancy from syringoma. Another feature is that the tumour sets in a dense fibrous stroma, although the mechanism underlying this feature has not been clarified. 1 We here report a case of syringoid eccrine carcinoma forming circumscribed tumour nests with abundant stroma. A 64-year-old woman presented with 3 months history of a 10-mm diameter, painful, firm plaque on the right forehead. The lesion surgically removed showed multiple tumour nodules proliferating in dermis and subcutaneous adipose tissue (Fig. 1a). Each nodule includes abundant stromal tissue (Fig. 1b). The tumour consisted of basaloid cells arranging in narrow cords and partially forming ductular structure. Tadpole-like forms were sometimes observed. Mitoses were also found (Fig. 1c) but not prominent. Squamous or follicular differentiation was not seen. Immunohistochemical staining of tumour cells showed positive reactivity to epithelial membrane antigen and carcinoembryonic antigen (Fig. 1d) but negative reactivity to S-100 protein. The stroma positively stained for type 1 collagen but not type 2, type 3 and type 4 collagens, fibronectin, laminin and vimentin. In addition, the immunostaining of tumour cells did not detect expression of type 1 collagen and fibrosis-associated cytokines including fibroblast growth factor 1 and 2, transforming growth factor-beta, platelet-derived growth factor, hepatocyte growth factor/scatter factor and insulin-like growth factor 1. This case required differential diagnosis with microcystic adnexal carcinoma, which is also surrounded by a dense fibrous stroma and infiltrates into the deeper tissue. 1 Absence of keratinfilled cyst and follicular differentiation resulted in the diagnosis of syringoid eccrine carcinoma; nevertheless, the assessment was difficult. In both syringoid eccrine carcinoma and microcystic adnexal carcinoma, the surrounding stroma is generally ill defined because tumour nests proliferate chiefly in dermis. It has therefore been unknown whether the stroma surrounding tumour nests is induced by a direct effect of tumour-derived cytokine or non-specific