bromochloroacetic-acid and Skin-Diseases--Infectious

This study was undertaken to characterize the effects of constitutive expression of the hedgehog transcriptional activator, Gli2, in porcine skin. The keratinocyte-specific human transgene, K5-hGli2 Delta N, was used to produce transgenic porcine lines via somatic cell nuclear transfer techniques. In mice, K5-hGli2 Delta N induces epithelial downgrowths resembling basal cell carcinomas. Our porcine model also developed these basal cell carcinoma-like lesions, however gross tumor development was not appreciated. In contrast to the murine model, diffuse epidermal changes as well as susceptibility to cutaneous infections were seen in the swine model. Histologic analysis of transgenic piglets revealed generalized epidermal changes including: epidermal hyperplasia (acanthosis), elongated rete ridges, parakeratotic hyperkeratosis, epidermal neutrophilic infiltration, capillary loop dilation and hypogranulosis. By 2 weeks of age, the transgenic piglets developed erythematic and edematous lesions at high contact epidermal areas and extensor surfaces of distal limb joints. Despite antibiotic treatment, these lesions progressed to a deep bacterial pyoderma and pigs died or were euthanized within weeks of birth. Non-transgenic littermates were phenotypically normal by gross and histological analysis. In summary, constitutive expression of the human hGli2 Delta N in keratinocytes, results in cutaneous changes that have not been reported in the K5-hGli2 Delta N murine model. These findings indicate a need for a multiple species animal model approach in order to better understand the role of Gli2 in mammalian skin.

Topics: Animals; Animals, Genetically Modified; Animals, Suckling; Epidermis; Female; Fibroblasts; Genetic Predisposition to Disease; Hair Follicle; Humans; Keratins; Kruppel-Like Transcription Factors; Male; Mice; Nuclear Proteins; Phenotype; Pyoderma; Recombinant Fusion Proteins; Skin Diseases, Infectious; Species Specificity; Sus scrofa; Swine; Transgenes; Zinc Finger Protein Gli2

Biopsy specimens from skin of 99 patients with 26 different dermatoses and 17 specimens from normal skin were labeled with regard to the reactivity of keratinocytes with the monoclonal natural killer-associated antibody anti-Leu-11b by means of the avidin-biotin-peroxidase complex method. Reactivity occurred in 64.7% of the preparations from normal skin and in 84.8% of the preparations from diseased skin. The membranes of the subcorneal keratinocyte layers were labeled regularly. In some of the preparations cytoplasmic reactivity and labeling of the basement membrane zone occurred in addition. Most labeled preparations and the highest labeling intensities were shown in the skin tumors and in the infectious dermatoses. The biologic significance of this finding is discussed.

Topics: Antibodies, Monoclonal; Antigens, Surface; Epidermal Cells; Epidermis; Humans; Immunohistochemistry; Keratins; Killer Cells, Natural; Lymphocyte Function-Associated Antigen-1; Skin Diseases; Skin Diseases, Infectious; Skin Neoplasms

Adenoviruses are pathogenic for certain stratified squamous epithelia. The sites most frequently involved are the upper respiratory tract and oropharynx. Adenovirus infections of the epidermis are quite rare. We examined the virus-cell interactions of adenovirus type 2 (Ad2) and cultured human keratinocytes grown from a variety of body sites. Our intent was to explore the nature of the apparent epithelium-specific susceptibility to Ad2. In brief, we found that in vitro viral susceptibility of the keratinocytes could be reliably predicted based on whether the cells originated from an epidermal or oropharyngeal surface. Ad2 proceeded through a complete vegetative cycle when used to infect cultured keratinocytes from oropharyngeal sites (e.g., gingiva and soft palate). In contrast, Ad2 infection was severely restricted in keratinocytes from epidermal sites (e.g., foreskin, abdomen, and buttock). These results demonstrate that the in vitro response to infection with Ad2 reflects in vivo tissue-specific susceptibility. In vivo, cervical epithelium is rarely infected with Ad2 and yet in culture, cervical keratinocytes were fully permissive for Ad2 replication. We propose that the permissive or nonpermissive response to Ad2 may be regulated by a particular aspect of cell phenotype. Because the permissive responses seen in this study were all generated in keratinocytes from mucosal sites, it is possible the in vitro response to Ad2 reflects inherent differences between mucosal and epidermal keratinocytes.

Topics: Adenoviruses, Human; Cells, Cultured; Cytopathogenic Effect, Viral; Epidermis; Epithelium; Humans; Keratins; Mouth Mucosa; Skin Diseases, Infectious; Viral Proteins; Virus Replication

We wanted to evaluate the eventual expression of viral antigens and MHC class II products by keratinocytes as well as the alterations of epidermal Langerhans cells and dermal dendritic cells in viral lesions of skin and mucous membranes. Therefore we investigated 68 biopsy specimens of protracted viral lesions, such as warts, condylomas, and mollusca contagiosa, and of rapidly resolving viral lesions such as herpes simplex virus infection. For this we used immunohistochemical staining techniques and several monoclonal and polyclonal antisera. In most cases investigated viral antigens (human papilloma virus antigens or herpes simplex virus type 1 antigens) could be demonstrated in keratinocytic nuclei. Except for a few viral lesions in which epidermal Langerhans cells were rather numerous, epidermal Langerhans cells were reduced in number or absent in almost all viral lesions. Moreover, epidermal Langerhans cells and dermal dendritic cells showed changes in morphology, distribution, and immunophenotype. These alterations may be caused by a toxic effect of the virus on dendritic cells. HLA-DR+ keratinocytes could be identified in few viral lesions only; HLA-DQ+ keratinocytes were not seen. Possible explanations for this lack of MHC class II expression by keratinocytes are discussed.

Topics: Antigens, Viral; Dendritic Cells; Epidermis; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunohistochemistry; Keratins; Langerhans Cells; Mucous Membrane; Skin Diseases, Infectious; Virus Diseases

To determine a possible role of Langerhans cells in viral infection of skin, we studied the distribution of Langerhans and indeterminate cells in the lesional skin of mollusca contagiosa, verrucae vulgaris, plantar warts, and condylomata acuminata. A total absence of Langerhans and indeterminate cells was observed in molluscum contagiosum, but their number appeared to be normal or increased in the perilesional normal skin. Few Langerhans and indeterminate cells were seen in the suprabasal location in verrucae vulgaris and plantar warts, and normal numbers were noted in the perilesional skin. In contrast, a larger number of Langerhans and indeterminate cells reaching up to stratum granulosum were found in the condylomata acuminata. It is possible that alteration of keratinocytes by viral infection may effect the migration of Langerhans cells to the epidermis. The lack of Langerhans cells may lead to a paucity of inflammatory response (in particular, T cell-mediated response) to the cells infected with the virus.

Topics: Adolescent; Adult; Antibodies, Monoclonal; Condylomata Acuminata; Dendritic Cells; Epidermal Cells; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Langerhans Cells; Molluscum Contagiosum; Skin Diseases, Infectious; Warts

Topics: Acrodermatitis; Adolescent; Biopsy; Cell Membrane; Child; Cytoplasm; Endoplasmic Reticulum; Female; Herpesviridae Infections; Humans; Impetigo; Keratins; Male; Microscopy, Electron; Neutrophils; Skin; Skin Diseases, Infectious; Syndrome

Topics: Birth Injuries; Blister; Drug Eruptions; Epidermolysis Bullosa; Erythema; Female; Herpes Simplex; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Keratins; Listeria monocytogenes; Lupus Erythematosus, Systemic; Male; Maternal-Fetal Exchange; Miliaria; Nevus; Pregnancy; Pregnancy Complications; Rubella; Skin Diseases; Skin Diseases, Infectious; Stevens-Johnson Syndrome; Sucking Behavior; Syphilis, Congenital; Urticaria Pigmentosa

Topics: Corynebacterium; Hair; Humans; In Vitro Techniques; Keratins; Skin Diseases, Infectious

Topics: Axilla; Corynebacterium; Hair; Humans; Keratins; Skin Diseases, Infectious

Topics: Biopsy; Corynebacterium; Female; Humans; Keratins; Male; Microscopy, Electron; Nocardia Infections; Skin; Skin Diseases, Infectious