Keratinocyte expression of transgenic hepatocyte growth factor affects melanocyte development, leading to dermal melanocytosis.
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Using the epidermis-specific cytokeratin 14 promoter to deliver HGF exclusively from epidermal keratinocytes, we have examined the potential of hepatocyte growth factor (HGF) secreted from the normal environment to control morphogenesis. The transgenic mice displayed a significant increase of the number of melanocytes and their precursors in embryos starting not later than 16.5 dpc, and then after birth an explosive increase of dermal melanocytes started within 1 week, and these melanocytes were maintained throughout the entire life of the mice. Thus, HGF acts as a paracrine agent to promote survival, proliferation and differentiation of melanocyte precursors in vivo, and eventually causes melanocytosis. Loss of E-cadherin expression in dermal melanocyte precursors suggests that HGF caused dermal localization of melanocytes and their precursors by down-regulation of E-cadherin molecules. (+info)
A mutation in the V1 domain of K16 is responsible for unilateral palmoplantar verrucous nevus.
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Palmoplantar keratodermas are a group of heterogeneous diseases characterized by thickening, and marked hyperkeratosis, of the epidermis of the palms and soles. Palmoplantar keratodermas can be divided into four major classes: diffuse, focal, punctate, and palmoplantar ectodermal dysplasias. All forms are genetic diseases inherited as autosomal dominant disorders. We studied a patient exhibiting a localized thickening of the skin in parts of the right palm and the right sole, following Blaschko's lines, that does not fit into any classes already described. We sequenced the keratin 16 cDNA derived from skin biopsy material from affected and non affected palms. The keratin 16 cDNA sequence from lesional epidermis showed a 12 base pair deletion (309-320del), which deletes codons 104-107. The mutation is predicted to delete four amino acids, GGFA, from the V1 domain of the keratin 16 polypeptide, close to the 1A domain. Full-length keratin 16 cDNA sequence derived from the unaffected palm was completely normal, consistent with a postzygotic mutation as is suggested by the mosaicism observed. We defined this new clinical entity, "unilateral palmoplantar verrucous nevus", rather than localized or focal epidermolytic palmoplantar keratodermas, as the lesions are present only on one side of the body and follow Blaschko's lines. This study is a report of a mosaic mutation in keratin 16 and also the association of a mutation in the V1 domain of a type I keratin associated with a human disease. (+info)
Heavy metal poisoning in glass worker characterised by severe.
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The paper presents the clinical description of the masticatory organ and biochemical assessment of dental tissue in a patient employed in a glassworks for 20 years. During 12 years the patient has suffered baldness ("Alopecia areata") and atypical extensive and non-healing cutaneous lesions. Dental examination revealed changes typical of chronic poisoning by cadmium and bismuth compounds. (+info)
Therapeutic application of T cell receptor mimic peptides or cDNA in the treatment of T cell-mediated skin diseases.
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An 8-amino acid peptide encoding a sequence of the transmembrane region of the T cell receptor alpha chain (TCR-alpha) was shown to inhibit T cell function by preventing functional assembly of the T cell receptor (mimic peptide). To avoid systemic immunosuppression by peptide application in vivo, we used a topical application of the peptide. In the system of murine contact sensitivity, topical application of the peptide inhibited the elicitation of contact sensitivity following application of a contact allergen in sensitized animals. Alternatively, when naked DNA encoding the peptide sequence was injected into skin before application of a contact allergen to sensitized animals, local immunosuppression was also observed. To investigate the effects of this peptide in humans, patients with psoriasis, atopic eczema, lichen planus, or contact dermatitis were treated topically with mimic peptide or control peptide. All patients except for one reported a marked improvement or cure of their skin disease following application of the TCR-alpha peptide, but not controls. These data indicate that TCR-alpha peptide or cDNA treatment might be a proper treatment for human T cell-mediated dermatoses substituting for corticosteroids. (+info)
The pleiotropic effects of fibroblast growth factor receptors in mammalian development.
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In recent years the study of fibroblast growth factor receptors (FGFRs) in normal development and human genetic disorders has increased our understanding of some complex cellular processes. At least fifteen genetic disorders result from mutations within FGFR genes including skeletal dysplasias such as Apert syndrome and achondroplasia. In vitro experiments and the generation of animal models indicate that these mutations result in activation of the receptors and that FGFRs act as negative regulators of bone growth. FGFRs also play a role in wound healing and cancer. In this article, we review the expression of FGFRs in human development, the phenotypes resulting from FGFR mutations, and recent data identifying pathways downstream of the activated receptors. (+info)
Accumulation of CD4+CD7- T cells in inflammatory skin lesions: evidence for preferential adhesion to vascular endothelial cells.
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The CD7- subset of CD4+ memory T cells reflects a stable differentiation state of post-thymic helper T cells and represents a small subpopulation in circulating blood. We here demonstrate that CD7- T cells preferentially accumulate in skin lesions under chronic inflammatory conditions irrespective of the particular disease. As adhesion to vascular endothelial cells (EC) is required for migration of circulating lymphocytes into tissues, we analysed the adherence of purified subsets of CD4+ memory T cells to endothelial cells in vitro. Compared with CD4+CD7+ T cells, cells of the CD4+CD7- subset preferentially adhere to EC, which is moreover increased after prestimulation of EC with tumour necrosis factor-alpha (TNF-alpha). Stimulated EC increase expression of intercellular adhesion molecule-1 (CD54) and E-selectin (CD62E), the ligand of which, cutaneous lymphocyte-related antigen (CLA), is highly expressed in CD4+CD7- T cells but not in CD4+CD7+ T cells. LFA-1 is expressed in a bimodal distribution on CD4+CD7- T cells in contrast to CD4+CD7+ cells, whereas VLA-1, VLA-3, and VLA-5 are nearly similarly expressed in both T cell subsets. Our results imply that the preferred adherence of CD4+CD7- memory T cells to vascular EC, which is increased after long-term EC stimulation with TNF-alpha, is likely to facilitate their accumulation in various inflammatory skin lesions. (+info)
Cowden's disease diagnosed through mucocutaneous lesions and gastrointestinal polyposis with recurrent hematochezia, unrevealed by initial diagnosis.
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A 51-year-old man was admitted to our hospital because of hematochezia and painful keratotic plaques involving both hands. He had gastrointestinal polyposis, and a history of liver hemangiomas and thyroid tumor. Numerous papules on the face and papillomatosis on the oral mucosa were present. A diagnosis was made as a typical case of Cowden's disease according to the criteria proposed by Salem and Steck (J Am Acad Dermatol 8: 686, 1983). The patient was not correctly diagnosed initially in spite of typical manifestations of Cowden's disease, mainly due to his concomitant manifestations which occurred chronologically. (+info)
Very late onset small intestinal B cell lymphoma associated with primary intestinal lymphangiectasia and diffuse cutaneous warts.
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As only a handful of lymphoma cases have been reported in conjunction with primary intestinal lymphangiectasia, it is not yet clear if this association is merely fortuitous or related to primary intestinal lymphangiectasia induced immune deficiency. We report on two female patients, 50 and 58 years old, who developed small intestinal high grade B cell lymphoma a long time (45 and 40 years, respectively) after the initial clinical manifestations of primary intestinal lymphangiectasia. They presented with a longstanding history of fluctuating protein losing enteropathy, multiple cutaneous plane warts, and markedly dilated mucosal and submucosal lymphatic channels in duodenal biopsies. One had a large ulcerated tumour of the proximal ileum and the other diffuse ileal infiltration. In both, histological examination showed centroblastic high grade B cell lymphoma associated with duodenojejuno-ileal mucosal and submucosal lymphangiectasia. They were subsequently successfully treated with surgery and postoperative chemotherapy (AVmCP: adriamycin, cyclophosphamide, Vm26, and prednisolone), and chemotherapy alone (PACOB: adriamycin, cyclophosphamide, vincristine, bleomycine, and prednisolone), respectively. A three year follow up in both cases showed persistent diffuse lymphangiectasia without evidence of lymphoma. The present findings support the hypothesis that primary intestinal lymphangiectasia is associated with lymphoma development. (+info)