Normal Skin (normal + skin)

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Terms modified by Normal Skin

  • normal skin sample

  • Selected Abstracts


    Assessment of Optical Coherence Tomography Imaging in the Diagnosis of Non-Melanoma Skin Cancer and Benign Lesions Versus Normal Skin: Observer-Blinded Evaluation by Dermatologists and Pathologists

    DERMATOLOGIC SURGERY, Issue 6 2009
    METTE MOGENSEN MD
    BACKGROUND Optical coherence tomography (OCT) is an optical imaging technique that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell carcinoma (BCC) and in benign lesions and to assess the diagnostic accuracy of OCT in differentiating NMSC from benign lesions and normal skin. METHODS AND MATERIALS OCT and polarization-sensitive (PS) OCT from 104 patients were studied. Observer-blinded evaluation of OCT images from 64 BCCs, 1 baso-squamous carcinoma, 39 AKs, two malignant melanomas, nine benign lesions, and 105 OCT images from perilesional skin was performed; 50 OCT images of NMSC and 50 PS-OCT images of normal skin were evaluated twice. RESULTS Sensitivity was 79% to 94% and specificity 85% to 96% in differentiating normal skin from lesions. Important features were absence of well-defined layering in OCT and PS-OCT images and dark lobules in BCC. Discrimination of AK from BCC had an error rate of 50% to 52%. CONCLUSION OCT features in NMSC are identified, but AK and BCC cannot be differentiated. OCT diagnosis is less accurate than clinical diagnosis, but high accuracy in distinguishing lesions from normal skin, crucial for delineating tumor borders, was obtained. [source]


    Formaldehyde-releasers: relationship to formaldehyde contact allergy.

    CONTACT DERMATITIS, Issue 2 2009
    Contact allergy to formaldehyde, inventory of formaldehyde-releasers
    This is one of series of review articles on formaldehyde and formaldehyde-releasers (others: formaldehyde in cosmetics, in clothes and in metalworking fluids and miscellaneous). Thirty-five chemicals were identified as being formaldehyde-releasers. Although a further seven are listed in the literature as formaldehyde-releasers, data are inadequate to consider them as such beyond doubt. Several (nomenclature) mistakes and outdated information are discussed. Formaldehyde and formaldehyde allergy are reviewed: applications, exposure scenarios, legislation, patch testing problems, frequency of sensitization, relevance of positive patch test reactions, clinical pattern of allergic contact dermatitis from formaldehyde, prognosis, threshold for elicitation of allergic contact dermatitis, analytical tests to determine formaldehyde in products and frequency of exposure to formaldehyde and releasers. The frequency of contact allergy to formaldehyde is consistently higher in the USA (8,9%) than in Europe (2,3%). Patch testing with formaldehyde is problematic; the currently used 1% solution may result in both false-positive and false-negative (up to 40%) reactions. Determining the relevance of patch test reactions is often challenging. What concentration of formaldehyde is safe for sensitive patients remains unknown. Levels of 200,300 p.p.m. free formaldehyde in cosmetic products have been shown to induce dermatitis from short-term use on normal skin. [source]


    Use tests: ROAT (repeated open application test)/PUT (provocative use test): an overview

    CONTACT DERMATITIS, Issue 1 2000
    Tokio Nakada
    As one step in defining the clinical relevance of exposure to an allergen identified with patch testing, use tests (provocative use test (PUT), and repeated open application test (ROAT)) have been used. In 1/2 of the cases of seemingly reliable patch tests, use tests are negative, suggesting that the patient's biologic threshold of response had not been reached with open application dosing. Dramatic differences exist in regional skin reactivity and percutaneous penetration. Negative results of use tests on normal skin may become positive on diseased skin. To refine this assay further, more controlled observations and analysis of reaction differences between normal and damaged skin, and among regional anatomic sites might be performed. In addition, we require a standardized measurement for the results. Use testing has significant potential in refinement of the evidence-based diagnosis of clinical relevance. However, for general validation, we should fill the deficiencies described above. [source]


    Placebo-controlled evaluation of the irritant potential of tacalcitol (1,, 24-dihydroxyvitamin D3) in healthy volunteers

    CONTACT DERMATITIS, Issue 5 2000
    K. Schlotmann
    In the treatment of psoriasis with topical vitamin D3 analogues, lesional and perilesional irritation is the main side-effect. The aim of this study was to investigate whether local side-effects generated by tacalcitol, a vitamin D3 analogue, show concentration dependence. 3 different concentrations of tacalcitol (0.4; 4; 40 ,g/g ointment) and the vehicle were applied on normal skin of the back of 25 healthy volunteers under occlusive conditions for 5 days. Assessment of erythema, infiltration and scaling as well as measurement of transepidermal water loss (TEWL) was performed on days 1 to 5. On day 5, additional skin barrier tests (DMSO test, alkali resistance test) were performed. Erythema and slight infiltration, but no scaling, were observed in a number of subjects without significant differences. TEWL also did not show significant differences for the test formulations, though there was a tendency towards lower values in the untreated areas. In the skin barrier tests, a tendency towards higher alkali resistance in the test areas treated with 40 ,g tacalcitol/g ointment was detected. Thus, under occlusive conditions, the irritant potential of tacalcitol is very low. There is no convincing evidence of concentration dependence in irritation generated by tacalcitol when applied under occlusive conditions. [source]


    Assessment of Optical Coherence Tomography Imaging in the Diagnosis of Non-Melanoma Skin Cancer and Benign Lesions Versus Normal Skin: Observer-Blinded Evaluation by Dermatologists and Pathologists

    DERMATOLOGIC SURGERY, Issue 6 2009
    METTE MOGENSEN MD
    BACKGROUND Optical coherence tomography (OCT) is an optical imaging technique that may be useful in diagnosis of non-melanoma skin cancer (NMSC). OBJECTIVES To describe OCT features in NMSC such as actinic keratosis (AK) and basal cell carcinoma (BCC) and in benign lesions and to assess the diagnostic accuracy of OCT in differentiating NMSC from benign lesions and normal skin. METHODS AND MATERIALS OCT and polarization-sensitive (PS) OCT from 104 patients were studied. Observer-blinded evaluation of OCT images from 64 BCCs, 1 baso-squamous carcinoma, 39 AKs, two malignant melanomas, nine benign lesions, and 105 OCT images from perilesional skin was performed; 50 OCT images of NMSC and 50 PS-OCT images of normal skin were evaluated twice. RESULTS Sensitivity was 79% to 94% and specificity 85% to 96% in differentiating normal skin from lesions. Important features were absence of well-defined layering in OCT and PS-OCT images and dark lobules in BCC. Discrimination of AK from BCC had an error rate of 50% to 52%. CONCLUSION OCT features in NMSC are identified, but AK and BCC cannot be differentiated. OCT diagnosis is less accurate than clinical diagnosis, but high accuracy in distinguishing lesions from normal skin, crucial for delineating tumor borders, was obtained. [source]


    A Microscopic and Biomechanical Study of Skin and Soft Tissue After Repeated Expansion

    DERMATOLOGIC SURGERY, Issue 1 2009
    RAN HUO MD
    BACKGROUND Conventional expansion inadequately restores damaged skin for patients with large areas of skin deficiency or who lack sources of normal skin. These patients require repeated skin expansions, but little is known about the outcomes of this procedure. OBJECTIVE To evaluate the microscopic changes and biomechanical properties of skin and soft tissue after repeated expansion. MATERIALS AND METHODS We prepared three groups of six pigs each: a conventional expansion group, a repeated expansion group, and a blank nonsurgical control group. We measured histology, ultrastructure, basic fibroblast growth factor (bFGF), stress,strain, stress relaxation, and stress strength. RESULTS Skin obtained after conventional expansion and repeated expansion was basically healthy, but the microscopic and biomechanical properties differed from those of nonexpanded skin, especially in the repeated expansion group. CONCLUSION Repeated skin expansion involves growth under stress, simultaneous injuries, and further repairs, with fibers showing more injury signs than cells. This article describes the microscopic changes and biomechanical properties that occur after repeated expansion. [source]


    Curettage prior to Mohs' Micrographic Surgery for Previously Biopsied Nonmelanoma Skin Cancers: What Are We Curetting?

    DERMATOLOGIC SURGERY, Issue 1 2005
    Comparative Study, Prospective, Retrospective
    Background Curettage prior to excision and Mohs' micrographic surgery for nonmelanoma skin cancer is performed based on the assumption that the curette will remove softer, more friable tumor-infiltrated dermis and leave structurally intact normal skin. This assumption, however, has not been objectively examined in the dermatologic surgery literature. Objective We performed a study to examine the ability of curettage to selectively remove and delineate nonmelanoma skin cancer prior to Mohs' micrographic surgery. Methods The study included 150 previously biopsied basal cell and squamous cell carcinomas less than 1.5 cm in size. We conducted (1) a retrospective study of 50 tumors curetted prior to Mohs' surgery by a surgeon who routinely curettes preoperatively; (2) a prospective study in which a surgeon who routinely does not curette preoperatively curetted 50 tumors prior to Mohs' surgery; and (3) a comparative historical group of 50 noncuretted tumors treated with Mohs' surgery by the latter surgeon. All curetted tissue was evaluated histologically. Results Only 50% of the curetted tissue demonstrated the presence of tumor in the curettings, but in 76% of these, the curette left residual tumor at the surgical margins. Of the other 50% in which the curette removed only non,cancer-containing skin, 34% had tumor present at the surgical margin. Overall, the curette removed tumor, leaving no residual tumor at the surgical margins in only 12% of lesions. Comparison with historical noncuretted tumors operated on by the same surgeon showed that curettage did not affect the mean number of stages or the proportion of tumors requiring more than one stage for histologic clearance. Conclusion Although curettage may be helpful in debulking friable skin prior to Mohs' micrographic surgery, it does not reliably delineate the extent of a tumor. MING H. JIH, MD, PHD, PAUL M. FRIEDMAN, MD, LEONARD H. GOLDBERG, MD, AND ARASH KIMYAI-ASADI, MD, HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMERCIAL SUPPORTERS. [source]


    Human Papillomavirus and Overexpression of P16INK4a in Nonmelanoma Skin Cancer

    DERMATOLOGIC SURGERY, Issue 3 2004
    Ingo Nindl PhD
    Background. P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV),infected cervical (pre)cancer lesions. Objective. To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. Methods. Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only ,-globin,positive patients were included in this study. Results. HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. Conclusion. P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted. [source]


    Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic foot ulcers

    DIABETIC MEDICINE, Issue 6 2002
    E. B. Jude
    Abstract Aims To study the distribution of transforming growth factor-beta (TGF-,) 1, 2 and 3, and TGF-, receptor types I and II in diabetic foot ulcers, diabetic skin and normal skin by immunohistochemistry, immunofluorescence and Western blotting. We also compared the TGF-,s with those of chronic venous ulcers. Methods Skin biopsies were obtained from the leg or the foot of non-diabetic and diabetic subjects, and from the edge of diabetic foot ulcers and chronic venous ulcers. Distribution (by immunofluorescence and immunocytochemistry) of TGF-, 1, 2 and 3 and TGF-, receptors (RI and RII) was done by staining 8-µm skin sections using appropriate antibodies. Protein levels of TGF-, were measured by Western blot analysis. Results TGF-,3 expression was increased in the epithelium at the edge of diabetic foot ulcers, being more intense than diabetic and normal skin (P = 0.03, 0.02, respectively), as was its expression in venous ulcers compared with normal skin. However, TGF-,1 expression was not increased in diabetic foot ulcers and chronic venous ulcers, and was comparable to diabetic and normal skin. There was also no increase for the receptors in diabetic foot ulcers. Conclusion The lack of TGF-,1 up-regulation in both diabetic foot ulcers and venous ulcers may explain the impaired healing in these chronic wounds, and could represent a general pattern for chronicity. [source]


    Gene expression demonstrates increased resilience toward harmful inflammatory stimuli in the proliferating epidermis of human skin wounds

    EXPERIMENTAL DERMATOLOGY, Issue 8 2010
    K. Markus Roupé
    Please cite this paper as: Gene expression demonstrates increased resilience toward harmful inflammatory stimuli in the proliferating epidermis of human skin wounds. Experimental Dermatology 2010; 19: e329,e332. Abstract:, We examined the epidermal gene expression during the proliferative phase of wound healing. Matrix metalloproteases were the group of proteases most prominently up-regulated in skin wounds, whereas serine protease inhibitors were the most strongly up-regulated protease inhibitors. Furthermore, we found down-regulation of genes involved in the extrinsic pathway of apoptosis. This together with the up-regulation of inhibitors of leukocyte serine proteases likely represents a protective step to ensure survival of keratinocytes in the inflammatory wound environment. The down-regulation of proapoptotic genes in the extrinsic pathway of apoptosis was not accompanied by a down-regulation of receptors indicating that the keratinocytes in skin wounds did not become less responsive to external stimuli. Examining the transcription factor binding sites in the promoters of the most differentially expressed genes between normal skin and skin wounds a significant overrepresentation of binding sites were found for STAT-5, SRY and members of the FOXO-family of transcription factors. [source]


    Decreased expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor in basal cell carcinomas

    EXPERIMENTAL DERMATOLOGY, Issue 11 2008
    Pierre E. Stoebner
    Abstract:, Thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor is associated with tumor angiogenesis. We evaluated the TP mRNA and protein expression in basal cell carcinomas (BCC) and in various skin tumors including numerous BCC histological simulants. Immunohistochemistry was performed on 99 paraffin sections of formalin-fixed skin tumors using monoclonal antibodies (mAb) against TP. TP mRNA levels were measured by real time RT-PCR in whole BCCs (wBCC) and laser capture microdissected (LCM) BCC tumor cells. TP immunostaining was negative in all BCC variants and in most of the benign trichogeneic tumors studied. By contrast, TP was constantly immunodetected in actinic keratosis (AK), squamous cell carcinomas (SCC), syringomatous carcinomas (SC), basosquamous carcinomas (BSC) and melanomas. TP mRNA levels were low and statistically not different in wBCC and normal skin but were strongly downregulated in LCM-BCC as compared with LCM-normal epidermis. We concluded that (i) anti-TP mAb is an useful marker to differentiate BCC from AK, SCC, BSC and SC but not from trichoblastic tumors, (ii) the lack of TP protein expression in BCC tumoral cells is linked to transcriptional regulatory mechanisms, (iii) the low TP mRNA levels in whole BCC may be related to the low intra-tumoral microvessel density, the slow growth and the very low metastatic potential of these tumors. [source]


    Expression of the human Cathepsin L inhibitor hurpin in mice: skin alterations and increased carcinogenesis

    EXPERIMENTAL DERMATOLOGY, Issue 9 2007
    Markus Walz
    Abstract:, The serine protease inhibitor (serpin) hurpin (serpin B13) is a cross class-specific inhibitor of the cysteine protease Cathepsin (Cat) L. Cat L is involved in lysosomal protein degradation, hair follicle morphogenesis, epidermal differentiation and epitope generation of antigens. Hurpin is a 44 kDa protein which is expressed predominantly in epidermal cells. In psoriatic skin samples, hurpin was strongly overexpressed when compared with normal skin. Keratinocytes overexpressing hurpin showed increased resistance towards UVB-induced apoptosis. To further analyse the functional importance of this inhibitor, we have generated transgenic mice with deregulated Cat L activity by expressing human hurpin in addition to the endogenous mouse inhibitor. The three independent transgenic lines generated were characterized by identical effects excluding insertional phenotypes. Macroscopically, mice expressing human hurpin are characterized by abnormal abdominal fur. The number of apoptotic cells and caspase-3 positive cells was reduced after UV-irradiation in transgenic animals compared with wild-type mice. Interestingly, after chemical carcinogenesis, transgenic mice showed an increased susceptibility to develop skin cancer. Array analysis of gene expression revealed distinct differences between wild-type and hurpin-transgenic mice. Among others, differentially expressed genes are related to antigen presentation and angiogenesis. These results suggest an important role of Cat L regulation by hurpin which might be of clinical relevance in human skin diseases. [source]


    Expression pattern of somatostatin receptor subtypes 1,5 in human skin: an immunohistochemical study of healthy subjects and patients with psoriasis or atopic dermatitis

    EXPERIMENTAL DERMATOLOGY, Issue 12 2006
    Lena Hagströmer
    Abstract:, In psoriasis and atopic dermatitis, the inflammatory events have neurogenic components and the neuropeptides modify the functions of immuno-active cells in the skin. Somatostatin is a neuropeptide with several neuroendocrine and immunomodulating properties and mediates its actions by five distinct subtypes of G-protein-coupled receptors (SSTR1-5). This study describes the distribution of SSTR1,5, analysed with immunohistochemistry, in psoriasis, atopic dermatitis and controls. Normal human skin and lesional skin from patients with psoriasis or atopic dermatitis showed many similarities, but also some differences, as regards SSTR expression. SSTR1,3 were strongly expressed in the epidermis of healthy skin, and in the skin of patients with psoriasis or atopic dermatitis. It is noteworthy that SSTR4 and 5 were strongly expressed in the epidermis of psoriasis patients, but weakly expressed in the epidermis of those with atopic dermatitis and normal skin. The intensity of the staining also varied considerably between the different layers of the epidermis, especially in psoriasis patients. In all cases, the dendritic cells, found mostly in the papillary and upper reticular dermis, showed a strong expression of SSTR1,4, but a weak expression of SSTR5. SSTR1,5 were strongly expressed in the sweat glands in all skin biopsies. Hair follicles and sebaceous glands expressed all five subtypes. Striated muscle fibres showed an intense positive expression of SSTR1,4, but a weak or negative expression of SSTR5. The wide distribution and expression pattern of all five SSTRs in human skin suggest that somatostatin is involved in the interactions between the nervous system and the skin. [source]


    Defining the caspase-containing apoptotic machinery contributing to cornification in human epidermal equivalents

    EXPERIMENTAL DERMATOLOGY, Issue 1 2006
    Vijaya Chaturvedi
    Abstract:, Whether terminal differentiation/stratum corneum formation of keratinocytes (KCs) represents a form of programmed cell death, utilizing mediators of classical apoptosis, is unclear. Apoptosis, an evolutionarily conserved death process, is comprised of extrinsic and intrinsic pathways, which converge using caspase 3. To define upstream and downstream caspases involved in terminal differentiation, we utilized human epidermal equivalents (EEs). Using submerged cultures comprised of human KCs, EEs were sequentially analyzed before and after being raised to an air/liquid (A/L) interface at 3,24 h intervals. At each time point, EEs were analyzed morphologically and for specific enzyme activity to distinguish different initiator (caspases 1, 2, 8, 9) and effector caspases (3, 6, 7). Terminal differentiation began at 6,8 h, as defined by stratum corneum with loricirin expression and completed at 18,24 h producing an epidermis resembling normal skin. Enzyme activity for caspases 1, 2, 3, 6, 7, 8, and 9 (but not 4, 5) was enhanced (>two-fold nmol/mg/h) at 3,6 h compared with submerged cultures. Processing of caspase 14 occurred at 18 h, and cleaved caspase 14 was increased at 24 h. Activated caspase 3-positive and terminal deoxynucleotidyl transferase-mediated nick end labeling-positive KCs were identified in EEs at 3,6 h corresponding to initiation sites of terminal differentiation. Addition of caspase inhibitors reduced levels of involucrin and loricrin in EEs raised to an A/L interface. We conclude caspases function as important death effectors strategically positioned at intersection of intrinsic and extrinsic pathways in KCs undergoing stratum corneum formation. [source]


    Stimulation of epidermal calcium gradient loss and increase in TNF-, and IL-1, expressions by glycolic acid in murine epidermis

    EXPERIMENTAL DERMATOLOGY, Issue 8 2005
    Se Kyoo Jeong
    Abstract:, In a previous study, we reported that ,-hydroxy acids (AHA), such as glycolic acid and lactic acid, did not induce any significant changes in transepidermal water loss for normal murine skin. The ultrastructural observations, however, showed that the extent of lamellar body exocytosis significantly increased. Because AHA can theoretically decrease the calcium ion concentration by chelation, topical AHA may induce the loss of epidermal calcium gradient by lowering the calcium ion concentration in the granulocytes and, subsequently, induce lamellar body secretion. The aim of this study is to verify that glycolic acid could modulate the epidermal calcium gradient and increase lamellar body exocytosis. Seventy per cent of glycolic acid aqueous solution was applied to the normal skin of hairless mice and biochemical and morphological studies were performed. The loss of epidermal calcium gradient was observed in glycolic-acid-applied skin of hairless mice and subsequent barrier function recovery processes, such as an increase in lamellar body secretion, were observed. The extracellular glycolic acid was found to inhibit the change in intracellular calcium ion concentration in response to extracellular calcium ion concentration changes in the cultured mouse keratinocyte in vitro. The protein and mRNA expressions of tumour necrosis factor-, and interleukin-1, in the murine epidermis were significantly increased after glycolic acid application. An in vitro study using cultured keratinocytes suggested that glycolic acid could lower the calcium ion concentration, at least in part, through the chelating effects of the glycolic acid on the cationic ions. [source]


    Stimulation of keratinocyte differentiation , a new role for the vanilloid receptor subtype 1 (VR1/TRPV1)?

    EXPERIMENTAL DERMATOLOGY, Issue 2 2005
    Sonja Ständer
    Vanilloids and endogenous cannabinoids mediate their actions via the vanilloid receptor subtype 1 (VR1/TRPV1), a non-selective cation channel, which is widely distributed in the central and peripheral nervous system. Only recently, VR1 has been shown to be expressed in keratinocytes in vitro and in vivo. However, a precise description of VR1 localization in epithelial cells was missing. To determine this, we investigated VR1-immunoreactivity as well as mRNA and protein expression in a series of biopsies from normal, diseased, and capsaicin-treated human skin. VR1 was found in epidermal keratinocytes, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands upon immunohistochemistry, RT-PCR and Western blot analysis. Interestingly, in diseased skin such as prurigo nodularis, psoriasis vulgaris, and atopic dermatitis, VR1 expression in keratinocytes correlated with the degree of epidermal differentiation. Enhanced VR1 immunoreactivity and protein content was found in prurigo nodularis in which epidermal keratinocytes are highly differentiated. Under effective capsaicin therapy of prurigo nodularis, the epidermis thinned and the distribution pattern of VR1 on epidermal keratinocytes normalized. In psoriasis vulgaris, a disease with disturbed epidermal differentiation, less intense immunostaining for VR1 was observed. This could be confirmed by western blot analysis showing less VR1 protein amount in comparison to prurigo nodularis although histologically both showed a thickened epidermis. In atopic dermatitis, which is characterized by a moderate epidermal hyperplasia only and regular differentiated keratinocytes, VR1 immunoreactivity was unchanged in comparison to normal skin. These findings suggest that VR1 may contribute to regular differentiation of keratinocytes. VR1 activation opens non-selective cation channels with high permeability to calcium, a ion that is crucially important for the synthesis of cornification proteins such as involucrin, fillagrin and loricrin. The role of VR1 in other epithelial cells of appendage structures remains to be determined. In summary, VR1 is widely distributed in the skin suggesting a central role for this receptor not only in nociception but also maturation and function of epithelial cells. [source]


    Genotype,phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1

    EXPERIMENTAL DERMATOLOGY, Issue 2 2002
    T. Hamada
    Abstract: We report a 42-year-old Japanese man with an unusual autosomal recessive genodermatosis. The clinical features comprised normal skin at birth, loss of scalp hair at 3-months of age after a febrile illness, progressive nail dystrophy during infancy, palmoplantar keratoderma starting around the age of 18 years and trauma-induced skin fragility and blisters noted from the age of 20 years. Skin biopsy of rubbed non-lesional skin revealed widening of spaces between adjacent keratinocytes from the suprabasal layer upwards. Electron microscopy demonstrated a reduced number of hypoplastic desmosomes. Immunohistochemical labeling showed a reduction in intercellular staining for the desmosome component plakophilin 1. Mutation analysis revealed a homozygous intron 11 donor splice site mutation in the plakophilin 1 gene, 2021+1 G>A (GenBank no. Z34974). RT-PCR, using RNA extracted from the skin biopsy, provided evidence for residual low levels of the full-length wild-type transcript (,8%) as well as multiple other near full-length transcripts, one of which was in frame leading to deletion of 17 amino acids from the 9th arm-repeat unit of the plakophilin 1 tail domain. Thus, the molecular findings help explain the clinical features in the patient, who has a similar but milder phenotype to previously reported patients with skin fragility-ectodermal dysplasia syndrome associated with complete ablation of plakophilin 1 (OMIM 604536). This new ,mitis' phenotype provides further clinicopathological evidence for the role of plakophilin 1 in keratinocyte cell,cell adhesion and ectodermal development. [source]


    Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and sezary syndrome)

    INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004
    Arnaud Cirée
    Abstract Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4+ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3+ CD4+ CD45RO+, a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth. © 2004 Wiley-Liss, Inc. [source]


    The role of angiogenesis, vascular maturation, regression and stroma infiltration in dormancy and growth of implanted MLS ovarian carcinoma spheroids

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2004
    Assaf Gilead
    Abstract MLS ovarian epithelial carcinoma multicellular spheroids xenografted subcutaneously in CD-1 nude mice displayed growth delay, or dormancy, of up to 52 days. In the study reported here, implanted MLS spheroids were used for testing the role of angiogenesis and vascular maturation in triggering the initiation of tumor progression. The kinetics and impact of neovascular maturation and functionality, in dormancy, and growth of MLS spheroid xenografts were studied noninvasively by BOLD contrast MRI. MR data were supported by histologic staining for biotinylated albumin as a blood pool marker and alpha-smooth muscle actin (alpha-SMA) as marker for perivascular mural cells. Although the tumor periphery showed higher levels of total and mature vasculature than normal skin, the fraction of mature out of the total vessels as detected by MRI vascular maturation index (VMIMRI) was significantly lower in the tumor both before and after tumor exit from dormancy. The neovasculature induced by the implanted spheroid was unstable and showed cycles of vessel growth and regression. Surprisingly, this instability was not restricted to the immature vessels, but rather included also regression of mature vessels. During dormancy, neovasculature was predominantly peripheral with no infiltration into the implanted spheroid. Infiltration of alpha-SMA positive stroma cells into the spheroid was associated with functional vascularization and tumor growth. Thus, stroma infiltration and vascular maturation are an important checkpoint linking the angiogenic switch with initiation of tumor progression. © 2003 Wiley-Liss, Inc. [source]


    Evaluation of coexistence of the Human Herpesvirus type 8 (HHV-8) infection and pemphigus

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2010
    Naser Tayyebi Meibodi Associate Professor
    Background, Human Herpesvirus type 8 (HHV-8) is a new member of the herpes virus family, first found in the tissue of acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma. Environmental factors including viral infection may play a role in the onset and/or development of pemphigus. Some studies based on polymerase chain reaction findings suggest an association between HHV-8 and pemphigus. The aim of this study is investigation of the association of pemphigus with HHV-8 and the relationship between inflammatory and acantholytic cells with HHV-8 infection. Methods, Tissue-extracted DNA from 41 paraffin-embedded skin tissues from patients first presenting with pemphigus was tested using nested PCR for the presence of HHV-8. A total of 37 cases had pemphigus vulgaris (PV) and 4 patients had pemphigus foliaceus (PF). For our control group, normal skin of 21 cosmetic surgery patients were included. Furthermore, microscopic slides with H&E staining were evaluated for the number of inflammatory and acantholytic cells per microscopic field. Results, Skin lesions from 13 of 37 patients (35.1%) with PV and 2 of 4 cases (50%) with PF were positive for HHV-8 DNA. All specimens in our control group were negative for this virus. Conclusion, HHV-8 infection might be a contributing factor in the initiation or development of pemphigus. [source]


    Expression of minichromosome maintenance 5 protein in proliferative and malignant skin diseases

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2007
    Houjun Liu
    Background, The entire minichromosome maintenance (MCM) family (MCM2,7) play roles in the initiation and elongation of DNA replication. Many studies have demonstrated that MCM proteins may be better indicators of a wide variety of proliferative or cancer cells in malignant tissues. Objectives, To characterize the pattern and frequency of MCM5 expression in proliferative and malignant skin diseases in comparison with those of proliferating cell nuclear antigen (PCNA). Methods, Twelve normal skin specimens, 12 specimens of psoriasis, 21 specimens of bowenoid papulosis (BP), 16 specimens of Bowen's disease (BD), 38 specimens of skin squamous cell carcinoma (SCC), and 11 specimens of basal cell carcinoma (BCC) were subjected to immunohistochemical staining for MCM5 and PCNA. Results, MCM5 protein was expressed in the lower layers of epidermis in psoriasis, while MCM5 protein were present throughout the tumor cells in BP, BD, and moderately/poorly differentiated SCC. MCM5 protein was preferentially expressed in the periphery of well-differentiated SCC or bigger nests of BCC, although some small nests of BCC seemingly showed diffuse staining patterns. The percentages of MCM5-positive cells were 15.7% in normal skin, 21.8% in psoriasis, 75.9% in BP, 83.8% in BD, 63.5% in well-differentiated SCC, 77.5% in moderately differentiated SCC, 79.8% in poorly differentiated SCC, and 21.2% in BCC in average. Well-differentiated SCC showed a significantly lower percentage of positive cells than did moderately differentiated SCC or poorly differentiated SCC. MCM5 staining basically show a similar staining pattern to that of PCNA, but more cells tended to be stained with MCM5 than with PCNA. Conclusions, Our results demonstrate pattern and frequency of MCM5 expression in various skin diseases and suggest that MCM5 may be a useful marker to detect cell proliferation in skin tissue sections. [source]


    Melanoma arising in a hairy nevus spilus

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2006
    lgül Zeren-Bilgin MD
    Cutaneous melanoma may develop de novo on normal skin or in contiguity with a potential melanocytic precursor. We report a 45-year-old man who presented with a recently developed nodule in a previously stable congenital nevus. Physical examination revealed a 10 × 18-cm lesion with speckled lentiginous pigmentation and terminal hairs on the lower back. A 2 × 2-cm suspicious nodule in the lesion was noted by the patient 2 months earlier. Histopathological evaluation of the nevus and the suspicious nodule revealed the characteristics of a melanocytic nevus and melanoma, respectively. It was interesting for the authors to observe terminal hairs in a lesion that was clinically ,speckled lentiginous' in appearance. This case report is a reminder that there may be great variation in the clinical appearance of nevus spilus, and thus dermatologists must be aware of these lesions as potential precursors of malignant melanoma. [source]


    Progressive macular hypomelanosis in Singapore: a clinico-pathological study

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2006
    Sujith Prasad W. Kumarasinghe MBBS
    Introduction, Progressive macular hypomelanosis (PMH), a condition of uncertain etiology, is characterized by asymptomatic hypopigmented macules predominantly located on the trunk. To date, there are no reports from South-East Asia concerning this condition. We sought to record the clinical features of PMH in Asian patients, identify etiologic factors, and study the structural and ultrastructural features of melanocytes in this disorder. Methods, Patients who presented to the National Skin Center with acquired, hypopigmented macules on the trunk, without a history of inflammation or infection, were recruited. Erythrocyte sedimentation rate (ESR), complete blood count, fasting blood glucose, liver function tests, skin scrapings for fungi, and skin biopsy specimens (from lesional and normal skin) were obtained. Biopsies were stained with hematoxylin and eosin (H&E), Fontana Masson, an immunohistochemical panel for identification of melanocyte differentiation antibodies (HMB 45, Melan A, and S100) and CD 68. Electron microscopy (EM) was also performed. The patients were evaluated every 3 months. Results, During a 9 month period, eight patients (all Chinese) presented with hypopigmented, ill-defined, confluent macules involving the lower aspect of the trunk. There were four men and four women, and the mean age was 25.9 years (range 19,45 years). Skin scrapings were negative for fungi and laboratory tests were normal. Microscopic evaluation of skin biopsy speciments showed reduced pigmentation of lesional as compared with normal appearing skin, but H&E-stained sections revealed only minimal histologic differences between lesional and normal skin. EM demonstrated a statistically significant (P = 0.047, Wilcoxon Signed Rank Test, Wilcoxon 95% CI 0.02,0.62) higher ratio of stage IV and late stage III (dark) melanosomes in normal vs. lesional skin. Conclusions, PMH may occur among young adults in Singapore. Its etiology is uncertain. The melanin content of lesional skin appears to be less than that in normal sites. EM shows a higher ratio of immature melanosomes in lesional vs. normal skin. [source]


    The development of cutaneous lesions during follow-up of patients with primary neuritic leprosy

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2005
    Sujai Suneetha PhD
    Background, Primary neuritic leprosy (PNL) is a rare form of leprosy where the characteristic skin lesions are absent. Investigations of apparently normal skin from the areas of sensory change have revealed microscopic evidence of nerve involvement. Clinical studies have found that a proportion of patients develop visible skin lesions during follow-up. The aim of the study was to perform a clinical and histological analysis of PNL patients who developed visible skin lesions during treatment and follow-up, to gain insight into the pathogenesis of the disease. Methods, Twenty-nine individuals in a series of 182 PNL patients developed visible skin lesions during follow-up. Analysis of the number, location, histology and time of onset of the new skin lesions in relation to the type and regularity of the treatment regimen were noted. A biopsy from the new skin lesion when available was compared with the nerve biopsy findings at the time of initial diagnosis. Results, Thirty-eight per cent of patients developed a single patch and 28% developed two patches. Over three-quarters of these were on the lower limb (47%) or the upper limb (29%). Sixty-two per cent of patients developed the lesions within 2 years of the onset of symptoms. Patients on regular treatment developed patches earlier than those on irregular treatment or no treatment. A skin biopsy from the new patch revealed borderline tuberculoid leprosy histology in 47% of the patients. Conclusions, The findings suggest that leprosy primarily affects the nerve and that a neuritic phase precedes the development of visible cutaneous lesions. [source]


    Cranial fasciitis of childhood

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2003
    Margarita Larralde MD
    A 2-month-old boy was seen at our pediatric dermatology department with a history of a tumoral lesion of the scalp since his birth. On examination he had a single, ovoid, firm, 2 × 1.8-cm painless subcutaneous mass on the temporal left calvarium, covered by normal skin (Fig. 1). It had experienced explosive growth in the preceding 2 weeks. There was no history of previous trauma in the area. The remainder of the examination was normal. Roentgenographic studies of the skull revealed a soft-tissue mass without involvement of the underlying bone. Ultrasonography of the lesion showed it to be an echolucid tumor. With the presumed diagnosis of dermoid cyst we sent the patient for surgical removal. At surgery, the lesion did not have the typical surgical appearance of a cyst. The histopathologic exam of the specimen was interpreted as cranial fasciitis of childhood (Fig. 2). Immunohistochemistry showed diffuse positivity for vimentin and muscle actin. After 1 year the patient is free of lesions. Figure 1. Lesion at the temporal left calvarium Figure 2. Proliferation of loosely arranged spindle cells in a loose myxoid stroma (H&E stain, × 40) [source]


    An interesting case of colocalization of segmental lichen planus and vitiligo in a 14-year-old boy

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2002
    Kabir Sardana MD
    A 14-year-old boy had segmental vitiligo (L3,4) on the right thigh and leg for 4 years, and was advised to apply topical clobetasol propionate, 0.05%, in the night, with daily sun exposure for 10 min, as he refused to comply with topical psoralens. As there was no response to therapy even after 3 months, the patient stopped the steroid cream but continued with the sun exposure. Subsequently, the patient noticed gradual-onset, itchy, violaceous, pigmented, raised lesions superimposed on the vitiligo macules. Cutaneous examination revealed violaceous, polygonal papules, 0.5 × 0.5 cm in size, some of which coalesced to form discrete violaceous plaques, confined to areas of vitiligo, with a clear-cut demarcation from normal skin (Fig. 1). The scalp, palms, soles, nails, and mucosa were normal. Histopathology of the polygonal papules revealed hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis with saw toothing of the rete ridges, basal cell liquefaction, and a band-like lymphocytic infiltrate (Fig. 2), consistent with lichen planus. The patient was subsequently prescribed fluticasone propionate (0.05%) ointment once daily for the lesions of lichen planus. There was a marked improvement in the lesions of lichen planus after 1 month. Figure 1. Violaceous papules of lichen planus colocalized on vitiligo macules with associated leukotrichia seen on the right leg Figure 2. Histopathology reveals hyperkeratosis, wedge-shaped hypergranulosis, irregular acanthosis with saw toothing of the rete ridges, basal cell liquefaction, and a band-like lymphocytic infiltrate (hematoxylin and eosin, × 40) [source]


    Application of computerized image analysis in pigmentary skin diseases

    INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2001
    Eun-So Lee MD
    Background Melanocyte number and the amount of melanin pigment are related to diagnosis and treatment of pigmentary skin diseases. Various histologic methods are used, such as Fontana-Masson stain for melanin pigment or immunohistochemical stain for melanocytes. Recently, computerized image analysis has been applied to many fields to avoid interobserver bias. In this study, we applied a computerized image analysis to assess the melanin content and melanocyte density of human epidermis. Methods We evaluated the skin biopsy specimens (paraffin blocks) from normal human skin (33 ± 6.6, n = 11) and diseased skins; vitiligo (32 ± 10.0, n = 8), melasma (35 ± 8.6, n = 11), and lentigo senilis (40 ± 7.2, n = 11) (mean age ± SD). Each specimen was stained with Fontana,Masson for melanin pigments and immunohistochemical method for melanocytes. Quantitative analysis of melanin pigment and melanocyte number (density) were investigated through two methods: (1) two dermatologists measured the visual scales; and (2) computerized image analysis was used to measure melanin content indices (MCI). The data were evaluated using one-way anova. Results The visual scale of the Fontana,Masson stain was the highest for lentigo senilis (3.8 ± 0.40), followed by melasma (2.6 ± 0.67), normal skin (1.8 ± 0.60) and vitiligo (0) (P < 0.05). These findings were consistent with objective measurements made by computerized image analysis. MCI values were 120.3 ± 20.74 for lentigo senilis, 81.1 ± 19.27 for melasma, 45.5 ± 16.92 for normal skin, and 0.3 ± 0.30 for vitiligo in decreasing order (P < 0.05). MC/1E (melanocyte number per 1 mm epidermis) was about two fold larger in lentigo senilis (18.1 ± 8.92) than melasma (9.7 ± 2.40) or normal skin (9.3 ± 2.67) (P < 0.05). MC/1B (melanocyte number per 1 mm basal layer) was about 1.5 fold higher in lentigo senilis (13.5 ± 4.17), compared to normal skin (9.0 ± 3.55) (P < 0.05). Melasma showed increased melanocyte numbers compared to normal skin, but it was not statistically significant (P > 0.05). Conclusion We believe this computerized image analysis could be useful tool for diagnosis and comparison of interval changes in pigmentary diseases like melasma or lentigo senilis by quantifying melanin pigments or melanocytes in skin biopsy specimens. [source]


    What is a role of haeme oxygenase-1 in psoriasis?

    INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2007
    Current concepts of pathogenesis
    Summary The skin is constantly exposed to endogenous and environmental pro-oxidant agents, which lead to harmful generation of reactive oxygen species (ROS). Healthy skin, being a potential target for oxidative stress, is equipped with a large number of defence mechanisms including antioxidant systems. This protection can be corrupted by an imbalance between ROS and antioxidants with pathological level of oxidants prevailing. There is a great body of evidence indicating that some inflammatory skin diseases, such as psoriasis, are mediated by oxidative stress. Keratinocytes of normal skin, the primary target for pro-oxidant agents, show strong expression of ROS-detoxifying enzymes. In addition, normal keratinocytes express haeme oxygenase (HO), an enzyme which might be involved in the protection of cells against oxidative stress. HO (inducible HO-1, constitutive HO-2 and HO-3) is the rate-limiting enzyme in haeme catabolism, which leads to the generation of biliverdin, iron, and carbon monoxide. HO-1 is a stress-responsive protein whose expression is induced by various oxidative agents. HO-1 is known for its cytoprotective, antioxidant and anti-inflammatory properties. Interestingly, a strong overexpression of HO-1 was observed in psoriatic skin. However, the role of HO-1 in psoriasis remains unclear. In this review, we will discuss some current concepts concerning pathogenesis of psoriasis and the contribution of HO-1 in skin inflammation to show the relationships between HO-1, ROS and cytokine network in psoriatic skin. We will try to answer a question whether enhanced HO-1 expression in keratinocytes results in beneficial or detrimental effect on the development and severity of psoriatic lesions. [source]


    EPUAP classification system for pressure ulcers: European reliability study

    JOURNAL OF ADVANCED NURSING, Issue 6 2007
    Dimitri Beeckman
    Abstract Title.,EPUAP classification system for pressure ulcers: European reliability study Aim., This paper is a report of a study of the inter-observer reliability of the European Pressure Ulcer Advisory Panel pressure ulcer classification system and of the differential diagnosis between moisture lesions and pressure ulcers. Background., Pressure ulcer classification is a valuable tool to provide a common description of ulcer severity for the purposes of clinical practice, audit and research. Despite everyday use of the European Pressure Ulcer Advisory Panel system, its reliability has been evaluated in only a limited number of studies. Methods., A survey was carried out between September 2005 and February 2006 with a convenience sample of 1452 nurses from five European countries. Respondents classified 20 validated photographs as normal skin, blanchable erythema, pressure ulcers (four grades), moisture lesion or combined lesion. The nurses were familiar with the use of the European Pressure Ulcer Advisory Panel classification scale. Results., Pressure ulcers were often classified erroneously (, = 0·33) and only a minority of nurses reached a substantial level of agreement. Grade 3 lesions were regularly classified as grade 2. Non-blanchable erythema was frequently assessed incorrectly as blanchable erythema. Furthermore, the differential diagnosis between moisture lesions and pressure ulcers appeared to be complicated. Conclusion., Inter-observer reliability of the European Pressure Ulcer Advisory Panel classification system was low. Evaluation thus needs to focus on both the clarity and complexity of the system. Definitions and unambiguous descriptions of pressure ulcer grades and the distinction between moisture lesions will probably enhance clarity. To simplify the current classification system, a reduction in the number of grades is suggested. [source]


    Cultured human keratinocytes for optical transmission measurement

    JOURNAL OF BIOPHOTONICS, Issue 3 2010
    David Schaaf
    Abstract The challenges of measuring optical properties of human tissues include the thickness of the sample, homogenization, or crystallization from freezing of the tissue. This investigation demonstrates a method to avoid these problems by growing optically thin samples of human keratinocytes as a substitute for ex vivo epidermis samples. Several methods of growth were investigated. Resulting samples were measured on a spectrophotometer for transmission between 300 nm and 2600 nm. The efficacy of the cell growth was confirmed with histological examination of several cultured keratinocyte samples. Limitations were the requirement to measure samples immediately after removal from the incubation environment, and the absence of the irregular structures of normal skin such as hair and glands. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]