Erythema elevatum diutinum manifesting as a penile ulcer.
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Biomedical subjects
Publications and source records attributed to T Kanekura.
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We report a 75-year-old Japanese woman with classic Kaposi's sarcoma. PCR amplified human herpesvirus 8 (HHV-8) DNA sequences from her skin lesions and peripheral blood mononuclear cells (PBMC), but not her plasma, saliva or urine. An antibody test against HHV-8 lytic antigens was positive. Immunohistochemical staining detected latent antigen. There was no evidence of HHV-8 infection in her husband, sister or daughter. Genes coding for HHV-8-encoded viral interleukin-6, viral macrophage inflammatory protein I, viral G protein-coupled receptor, viral cyclin D and viral Bcl-2 were expressed to the same degree in both her skin lesion and PBMC. Latency-associated T0.7 mRNA and HHV-8-encoded viral tegument protein genes were expressed in her PBMC at levels lower than in the skin lesions. Based on the gene expression profile, we concluded that lytic HHV-8 infection was present in her skin lesions and PBMC.
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BACKGROUND: Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of alpha-galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL-3). To date, no direct detection of GL-3 by immunoelectron microscopy has been reported. OBJECTIVES: To examine whether GL-3 is accumulated exclusively in lysosomes of cutaneous cells using an anti-GL-3 monoclonal antibody (mAb) and immunoelectron microscopy. METHODS: Skin specimens from seven patients with Fabry disease were examined immunohistochemically by light and electron microscopy using an anti-GL-3 mAb. RESULTS: By light microscopy, the cytoplasm of vascular endothelial cells, eccrine gland cells, and perineurium was stained with mouse anti-GL-3 antibody. Electron microscopically, positive signals for GL-3 were limited to dilated lysosomes in the cytoplasm of endothelial cells, pericytes, eccrine gland cells, dermal fibroblasts and perineurium. CONCLUSIONS: Our results demonstrate that the cytoplasmic deposit in Fabry disease was GL-3 and the accumulated GL-3 was localized essentially to lysosomes.
We report an 18-month-old Japanese boy with selenium deficiency. He had dry skin with irregularly shaped, erythematous changes on the cheeks, groin, hip, and extremities, erosions on the external urethral and anal orifices, and sparse, short, thin, light-coloured hair. He had received parenteral nutrition for 5 months because of juvenile polyposis. At presentation, his serum selenium level was less than 2.0 microg/dL (normal range, 10.6-17.4 microg/dL). His skin lesions responded well to supplementary treatment with sodium selenite. His skin symptoms were similar to those attributable to a deficiency of zinc which, like selenium, is an essential trace element. According to the literature, selenium deficiency is responsible for cardiomyopathy, which was diagnosed in our patient. The clinical similarity to zinc deficiency and the literature yielded important clues for a diagnosis of selenium deficiency in this patient.
We report a case of classical juvenile pityriasis rubra pilaris (CJPRP) in a 15-year-old boy with Down syndrome. The rash was extensive, severe, accompanied by intense itching and responded to low-dose etretinate. Xerosis and cheilitis were also present, suggesting that keratinization defects associated with Down syndrome may be involved in the pathogenesis of CJPRP. PRP is a rare dermatological disorder and to the best of our knowledge, this is the first reported case of CJPRP in a patient with Down syndrome.
Adult Still's disease is characterized by a high spiking fever, transient skin rash, and polyarthralgia. Joint pain is one of the major complaints and is often intractable. We assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) therapy for treating arthralgia in adult Still's disease. A 33-year-old woman with adult Still's disease who suffered from recalcitrant arthralgia resistant to systemic corticosteroids was treated with GCAP therapy. She underwent five GCAP treatments at 5-day intervals. Her joint pain responded dramatically to the GCAP therapy, suggesting that GCAP may be useful for treating adult Still's disease. We present a detailed description of the patient and this novel therapy.
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The rash of systemic lupus erythematosus (SLE) is usually treated with topical corticosteroids, but prolonged use causes adverse cutaneous side-effects. We assessed the efficacy of topical tacrolimus for treating the skin lesions of SLE. Three patients with SLE affecting their facial skin applied 0.1% tacrolimus ointment on one side of their face twice daily for 3 weeks, in conjunction with a sunscreen cream. After 3 weeks, erythema on the treated side was ameliorated in all three patients compared with the untreated side. Although the study is preliminary, the results demonstrate that topical tacrolimus may be useful for treating the malar rash of SLE.
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The effects of a newly synthesized phospholipid polymer, poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) [poly(MPC-co-BMA)], on the water barrier function and water-holding capacity of the stratum corneum were examined by measuring transepidermal water loss (TEWL) and electrical conductance of the skin surface. On the backs of four NC mice, the epidermal permeability barrier was abrogated by cellophane tape stripping 30 times. The skin was then treated with 0.1% poly(MPC-co-BMA) or distilled water twice daily for the following 3 days. Poly(MPC-co-BMA) reduced TEWL significantly compared with the control after the first treatment (P = 0.044) and this effect was observed for 3 days. In human skin, water-holding capacity was measured at 5, 10, 15, 30 min and 1, 2, and 4 h after the application of poly(MPC-co-BMA) or distilled water to both volar forearms of 21 healthy volunteers. Skin treated with poly(MPC-co-BMA) showed significantly greater ability to retain water at all time points. Poly(MPC-co-BMA) is the first synthetic material that can enhance both the water barrier function and water-holding capacity of the stratum corneum. Our results indicate that this substance may be useful clinically in the treatment of dry skin.
OBJECTIVE: To investigate the expression of matrix metalloproteinases (MMPs) and its correlation with basigin/CD147 expression in metastatic lesions of cutaneous Sequamous cell carcinoma (SCC). METHODS: Expressions of MMPs and basigin/CD147 were examined by DAB and ALP immunohistochemical staining in 14 metastatic SSCs, and immunoblot analysis was used to observe the basigin/CD147 expression in metastatic samples. RESULTS: Normal skin and lymph nodes were basically negative for MMPs, but expressions of MMP-1, MMP-2, MMP-3 and MTl-MMP were increased in both tumor cells and stromal cells in metastatic SCC. Strongly positive or positive staining was observed in 4 or 8 of metastatic SCCs for basigin/CD147 in tumor cells respectively. Significant correlations were found between basigin/CD147 expression in tumor cells and MMP-1, MMP-2, MMP-3, MTl-MMP expression in surrounding stromal cells (p-values: 0.012, 0.024, 0.047 and 0.026, respectively). Immunoblot analysis revealed that basigin/CD147 expression increased in metastatic SCC. CONCLUSION: These results suggest that MMPs produced by both tumor cells and stromal cells play a role in metastasis of cutaneous SCC, and increased MMPs in stromal cells might be induced by basigin/CD147 expressed in tumor cells.
Basigin is a glycosylated transmembrane protein belonging to the immunoglobulin superfamily. It is thought to play roles in intercellular recognition involved in cell differentiation. We previously demonstrated at the light microscope level a correlation between basigin expression and epidermal differentiation. In the present study, the ultrastructural localization of basigin in normal human epidermal keratinocytes was investigated by immunoelectron microscopy. The basigin labeling was strongest on membranes of basal cells, weaker on prickle cells, and absent in granular and horny cells. On the membrane of basal cells, labeling was observed on the apical and lateral sides but not on the dermal side. Gold particles were mostly observed on the surface of microvilli, especially on their tips. There were fewer on the intermicrovillous membrane and they were absent on the desmosome. These results are consistent with our previous report that basigin expression is correlated with differentiation of epidermal keratinocytes. Microvilli on basal and suprabasal keratinocytes might play roles in the differentiation of keratinocytes through basigin on the tips of microvilli.
BACKGROUND: Basigin is a glycosylated transmembrane protein belonging to the immunoglobulin superfamily and is thought to be associated with cell development and differentiation. We investigated the relation between Basigin expression and epidermal development in this study. METHODS: Basigin expression was immunohistochemically investigated during organogenesis of human skin and in human basal cell carcinoma (BCC). RESULTS: Human fetal skin showed negative staining at 10 weeks of gestation. At 20 weeks, the cytoplasm and membranes of adnexal germ and hair follicular cells were strongly positive, while epidermal basal cells showed weakly positive staining. After birth, basal cells, suprabasal cells, anagen hair follicular cells and eccrine glandular cells showed positive staining. Membranes of basal cells expressed more Basigin compared to other cell components. Basigin was not detectable in granular cells and telogen hair follicular cells. Sixteen of 30 BCCs were entirely negative for Basigin. However, cells at budding areas of tumor masses were positive in 14 of the 30 BCCs. CONCLUSIONS: These findings suggest that 1) Basigin is associated with epidermal proliferation and differentiation, 2) most parts of BCCs might be derived from early fetal epidermal basal cells, and 3) that a part, only the budding area of BCCs, has the characteristics of epithelial germ cells.
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OBJECTIVE: We and others reported on the beneficial effects of combined therapy using 8-methoxypsoralen and long wave ultraviolet light (PUVA therapy) in the treatment of scleroderma. We now investigate the mechanism by which PUVA therapy is effective by comparing interleukin 1beta (IL-1beta) mediated signal transduction in scleroderma fibroblasts and those from normal skin. METHODS: Prostaglandin E2 (PGE2) production and expression of cytosolic phospholipase A2 (cPLA2), cyclooxygenase (COX)-1, and COX-2 (enzymes that regulate PGE2 production) were examined in untreated and IL-1beta treated fibroblasts from scleroderma involved and normal skin. The effect of UVA irradiation on enzyme expression and PGE2 production was examined. PGE2 was measured by a competitive radioimmunoassay and enzyme expression was analyzed by Western immunoblotting and Northern blotting. RESULTS: Constitutive PGE2 production was significantly upregulated and IL-1beta induced PGE2 production was increased by the enhancing expression of both COX-2 mRNA and protein in fibroblasts from scleroderma involved skin; PGE2 production and COX-2 expression were inhibited by UVA irradiation. CONCLUSION: Enhanced PGE2 production regulated by COX-2 expression in scleroderma fibroblasts may contribute to the development of this disorder. PUVA therapy might exhibit its beneficial effect, at least in part, by inhibiting COX-2 expression transcriptionally and translationally, with subsequent inhibition of PGE2 production.
We recently demonstrated that the constitutive expression of cyclooxygenase (COX)-2 protein and prostaglandin E(2) (PGE(2)) biosynthesis were significantly enhanced in human skin epidermal cancer cells and that cancer cell growth was effectively inhibited by the suppression of COX-2 expression by transfection with COX-2 antisense oligonucleotide. The purpose of this study was to search for agents which suppress COX-2 expression and examine their effects on cell growth. Since retinoids and antioxidants have been used for chemoprevention of cancers in several tissues, the effects of these agents on COX-2 expression and PGE(2) biosynthesis in skin squamous carcinoma cells were investigated. Treatment with a retinoid (9-cis-retinoic acid (9-cis-RA)) or an antioxidant (pyrrolidinedithiocarbamate (PDTC)) suppressed COX-2 expression and PGE(2) biosynthesis in a concentration-dependent manner. Cell growth was significantly inhibited by 9-cis-RA and PDTC. These results suggest that 9-cis-RA and PDTC may be useful in preventing skin cancer growth and that COX-2 is involved in their protective effects on skin carcinogenesis.
Cyclooxygenase (COX)-2 is one of the rate-limiting enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Recent studies have shown enhanced expression of COX-2 in cancer cells of several tissues. We investigated the expression of COX-2 and prostaglandin (PG) E((2)) production in two human skin epidermal cancer cell lines: cutaneous squamous cell carcinoma, HSC-5, and eccrine carcinoma, EcCa. Both COX-2 expression and PGE((2)) production were significantly enhanced in cancer cell lines compared with the non-tumorigenic human keratinocyte cell line, HaCaT. In order to determine the role of COX-2 in the proliferation of HSC-5 and EcCa, the growth of untreated cells and cells transfected with COX-2 antisense oligonucleotide was compared using the MTT assay. Transfection with the antisense oligonucleotide suppressed COX-2 protein expression and significantly inhibited cell growth. The effect of a selective inhibitor of COX-2, NS398, was compared with the effect of the antisense oligonucleotide in order to see whether COX-2 expression and prostaglandins have selective effects on cell growth. COX-2 expression was unchanged by NS398 treatment, whereas NS398 inhibited cell growth to a certain extent. The degree of growth inhibition was greater with the antisense oligonucleotide than with NS398. Our findings indicate that COX-2 protein expression is enhanced in skin epidermal cancer cells and that COX-2 plays a pivotal role in regulating cell growth. Furthermore, inhibition of COX-2 expression had a more significant effect on growth suppression than inhibition of COX-2 catalytic activity, suggesting the existence of two different signal pathways via COX-2 in regulating cell growth.