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Human skin grafts from mixed lymphocyte culture-positive donors provide help for the rapid rejection of simultaneously transplanted skin grafts from mixed lymphocyte culture-negative donors.

The influence of grafting more than one skin transplant simultaneously on one recipient was investigated. When a mixed lymphocyte culture (MLC)-negative skin was transplanted along with an MLC-positive skin, the MLC-negative skin survived for a significantly shorter time than when transplanted alone. This indicated that the MLC-positive skin provided a stimulus that could provide help to reject the MLC-negative skin. This finding might be important clinically. When an MLC-negative transplant is given to a patient, one should not transfuse this patient with MLC-positive leukocyte-rich blood.

Graft Rejection↗

Combating bacterial resistance in skin and skin-structure infection: importance of beta-lactamase inhibition.

Serious skin and skin-structure infections may require parenteral antibiotic therapy. Such infections are generally polymicrobial, and they often involve both gram-positive and gram-negative aerobes as well as anaerobic bacteria. Effective treatment thus requires the use of a broad-spectrum antibiotic or combination therapy. The development of antibiotic resistance by clinically important pathogens has significantly increased the difficulty of treating skin and skin-structure infections. One of the major mechanisms of resistance observed in organisms likely to be associated with such infections is the development of beta-lactamases that inactivate beta-lactam antibiotics. Two approaches have been taken to combat this problem: the use of beta-lactam/beta-lactamase inhibitor combinations and the development of beta-lactamase-stable drugs. Both strategies have resulted in treatments that are clinically and bacteriologically effective in patients with skin and skin-structure infections. The use of one beta-lactam/beta-lactamase inhibitor combination, ampicillin/sulbactam, has been demonstrated to be more cost-effective than treatment with beta-lactamase-stable antibiotics, such as cefoxitin and imipenem/cilastatin, for this indication.

Anti-Bacterial Agents↗

Celecoxib reduces skin damage after radiation: selective reduction of chemokine and receptor mRNA expression in irradiated skin but not in irradiated mammary tumor.

Inflammatory cytokine and chemokine production is mediated, at least in part, by prostaglandin E (PGE2). Cyclooxygenases, COX-1 and COX-2, are two key enzymes in the conversion of arachidonic acid to PGE2. Radiation induces the overproduction of cytokines and chemokines, and it also increases PGE2 production, both locally and systemically. In this study, we tested the effects of a COX-2 inhibitor (celecoxib) after 50 Gy radiation of MCa-35 tumor and cutaneous tissues of C3H/He mice. Preclinical toxicity endpoints and associated alterations in chemokine production and cellular infiltrates were measured. Celecoxib was given by daily gavage (50 mg/kg for 15 days), with the first dose delivered either 2 hours before, 2 days after, or 7 days after a single dose of radiation. Celecoxib-treated animals had less inflammation of the dermis compared with saline-treated controls. Severe skin dermatitis occurred in 23.8% (5/21) of mice treated with 50 Gy, whereas only 17.6%, 5.3%, and 11.1% of mice in the 2-hour pre-, or the 2-day post-, and 7-day postirradiation groups, respectively, had severe dermatitis on day 20. The decreased skin toxicity scores were associated with a reduction of both blood vessels and focal necrosis in MCa-35 tumors. Celecoxib also significantly decreased C-C family chemokine (Rantes and MCP-1) mRNA expression in irradiated skin tissues, but not in tumor tissues, which was accompanied by a decrease in skin mRNA expression of both C-C (CCR2 and CCR5) and C-X-C (CXCR2 and CXCR4) chemokine receptors. A significant positive correlation was also found between skin damage (skin scores) and chemokine and its receptor mRNA expression in radiation-treated mice. Finally, celecoxib also decreased the infiltration of monocytes and neutrophils in locally irradiated tumor and surrounding normal tissue. The differential effects of celecoxib on inflammation help to explain the selective protection by celecoxib of irradiated cutaneous tissues without a concurrent protection of MCa-35 tumors.

Animals↗

Contrary intermittent skin release of complete syndactyly without skin graft in adults.

INTRODUCTION: There are many different surgical treatment techniques of complete syndactyly. Most of them are techniques involving using skin grafts. We developed a surgical technique that does not require skin grafts, which cause problems in the distal nail border pulp and interdigital web space. MATERIALS AND METHODS: Syndactyly release was performed in 12 web spaces of 11 adult male patients. The average age was 21. In addition to a zig-zag incision, contrary intermittent skin release was performed. Primary coverage of the interdigital web space and nail border pulp was achieved without skin graft. RESULTS: We obtained good results by the contrary intermittent skin release method that we developed, in adult complete syndactyly patients who had no chance for the surgical treatment due to several reasons, previously. CONCLUSION: With such a surgical technique, in our cases we obtained successful results, both cosmetic and functional. The presented technique is an alternative method for syndactyly release without using skin graft in adult patients.

Adult↗

Differential expression of collagens XII and XIV in human skin and in reconstructed skin.

Collagens XII and XIV localize near the surface of collagen fibrils and may be involved in epithelial-mesenchymal interactions as well as in the modulation of tissue biomechanical properties. Moreover, human skin fibroblasts cultured in monolayer are known to lose their ability to produce collagen XIV and to switch the transcription of collagen XII from the small splice variant (220 kDa) to the large (320 kDa), whereas the small form is the main form found in human skin. We have investigated the expression patterns of these two molecules in human skin as a function of donor age and anatomic site, by using immunohistology with specific monoclonal antibodies. We demonstrated changes in the expression patterns of collagens XII and XIV in human skin after birth. Moreover, in adult scalp skin, very strong staining of collagen XII fibril bundles was observed around hair follicles, in association with very low expression of collagen XIV. We also investigated the expression of collagens XII and XIV by fibroblasts and keratinocytes cultured in a reconstructed skin. In these culture conditions, fibroblasts recovered their ability to produce collagen XIV and re-expressed the small splice variant of collagen XII. These results could be explained by the deposition of large amounts of collagen fibrils by fibroblasts in this culture system. Thus, the re-expression of these collagens suggests that the deposition of banded collagen fibrils is a pre-requisite for the expression of collagen XIV and small variant of collagen XII.

Adult↗

Occurrence of cutaneous basal cell and squamous cell malignancies among those with a prior history of skin cancer. The Skin Cancer Prevention Study Group.

Non-melanoma skin cancer patients are believed to be at high risk of developing new skin malignancies; however, relatively few studies have actually examined this. Non-melanoma skin cancers, although generally not fatal, are responsible for significant morbidity and, if left untreated, can cause serious disfigurement and, in rare instances, death. Part of the difficulty in studying these tumors is that they are not routinely followed as rigorously as other cancers, and are excluded from most cancer registries. Prior studies have often included patients from a single dermatology practice of those treated with one type of therapy (e.g., Moh's surgery). Some studies did not entail active follow-up of patients but relied on reports to a registry or subsequent visits initiated by the patient or their physician. Other studies have been based solely on patients with complete follow-up information, excluding those who died or were lost to follow-up. Nearly all studies collected only a limited amount of information on each patient. In an attempt to overcome these limitations, we examined subsequent skin cancer occurrence among a group of patients followed as part of the Skin Cancer Prevention Study. In the following, we highlight some of the methodologic issues concerning the study of subsequent basal cell and squamous cell skin cancer risk, and the contribution of our work, along with that of others, in exploring clinical and etiologic questions pertaining to the occurrence of these malignancies.

Basal Cell Carcinoma↗

Urinary excretion of 5-S-cysteinyldopa in relation to skin type, UVB-induced erythema, and melanocyte proliferation in human skin.

5-S-Cysteinyldopa (5-S-CD) is found in all pigment-producing cells and is the major precursor of phaeomelanin. However, the melanocyte specificity of the compound has been questioned. In order to elucidate the origin of 5-S-CD, we have now systematically studied the relationship between the 5-S-CD excretion in urine and the size of the melanocyte organ, UV-induced melanocyte proliferation, skin type, and the erythemal reaction. The skin type had no influence on the basal excretion of 5-S-CD. There was no significant correlation between the basal 5-S-CD excretion and the size of the melanocyte organ; that is, the number of skin melanocytes and nevi. During the irradiation, subjects with skin type II developed a more pronounced erythema (p less than 0.01) and had a significantly higher 5-S-CD excretion than those with skin type III-IV (p less than 0.01). No correlation was found between 5-S-CD excretion and UV-induced melanocyte proliferation. The lack of correlation between the basal 5-S-CD excretion and skin type or number of melanocytes suggests that the basal 5-S-CD in urine is mainly of extra-melanocytic origin. Our findings favor the view that the increase in 5-S-CD excretion during UV irradiation is due to UV damage.

Adult↗

On a possible protective effect of HLA-A11 against skin cancer and keratotic skin lesions in renal transplant recipients.

Renal transplant recipients who have skin cancer potentially related to human papillomavirus were HLA typed with a special focus on HLA-A11, which in nonimmunosuppressed patients is negatively associated with the occurrence of virus-related carcinoma of the cervix. We found also a negative association between HLA-A11 and skin cancer; none of the 66 transplant recipients with skin cancer were positive for HLA-A11. As HLA-A11 seems to have a protective effect against skin cancer, we speculate that antigens induced by squamous cell carcinomas and possibly also by human papillomavirus may be efficiently presented through HLA-A11 to cytotoxic T cells. We also investigated a possible influence of other HLA alleles on the susceptibility of renal transplant recipients to skin cancer. The frequency of HLA-B27 was significantly higher in the transplant recipients with skin cancer, with a relative risk of 3.4 relative to healthy controls. No significant differences were found for other HLA class I or class II antigens.

Alleles↗

T-cell costimulatory capacity of oral and skin epithelial cells in vitro: presence of suppressive activity in supernatants from skin epithelial cell cultures.

Oral Langerhans cells (LC) have better T-cell costimulatory capacity than skin LC. In this study factors affecting this capacity have been assessed in a mixed epithelial cell lymphocyte reaction (MELR) assay. Flow cytometry analysis of freshly recovered cells revealed major histocompatibility complex (MHC) class II molecule expression on 7.5% of the oral epithelial cells and 9.7% of the skin epithelial cells. Monoclonal anti class II antibodies significantly reduced the T-cell proliferation in the MELR. Pretreatment of skin epithelial cells with interleukin-1beta, tumour necrosis factor-alpha or interferon (IFN)-gamma did not affect the MELR proliferation, but incubation with IFNgamma significantly suppressed the T-cell response. Transfer of supernatants from cultures of skin epithelial cells and allogeneic T cells to cultures of oral epithelial cells and T cells resulted in a reduced T-cell proliferation while supernatants from oral epithelial cells and T cells did not reduce proliferation. The higher proliferation in cultures of T cells and oral epithelial cells than in cultures containing skin epithelial cells may be due to the presence of a suppressive factor in the skin epithelial cell suspensions.

Animals↗

A comparison of the effects of captopril and enalapril on skin responses to intradermal bradykinin and skin blood flow in the human forearm.

1. The effects of captopril and enalapril on skin responses to intradermal injections of bradykinin and skin blood flow in the forearm were investigated in this randomised, double-blind, placebo-controlled, cross-over study. 2. Intradermal injections of 0, 1, 2.5 and 5 micrograms of bradykinin in 0.9% sodium chloride were made into the forearm of twelve healthy volunteers before and at 2, 6 and 24 h after single oral doses of 25 mg captopril, 10 mg enalapril or placebo. Forearm skin blood flow was measured by the technique of laser Doppler flowmetry (LDF) before the injections were made and the skin responses evaluated at 15 min after injections of bradykinin by measurement of cutaneous blood flow outside the induced weal, erythema area and weal volume. 3. The bradykinin-induced cutaneous responses measured by LDF, erythema area and weal volume increased with incremental bradykinin dose. Compared with placebo, captopril significantly augmented the cutaneous vasodilator effects of bradykinin, measured by LDF and erythema area, at 2 h and the weal responses at 2 and 6 h. Enalapril enhanced the vasodilator responses to bradykinin at 2 and 6 h and the weal responses at 2, 6 and 24 h. Neither captopril nor enalapril significantly affected forearm skin blood flow. 4. This study showed that captopril and enalapril potentiated the effects of intradermal bradykinin both with respect to blood flow changes and weal formation in keeping with effective kininase II inhibition and the time course of these changes are consistent with enalapril being a longer acting drug than captopril. Captopril and enalapril exerted no influence on forearm skin blood flow measured by LDF.

Adult↗

Skin susceptibility in uninvolved skin of hand eczema patients and healthy controls.

Basic physiological characteristics were examined in the uninvolved skin of 39 patients with hand eczema and in 39 healthy controls. Susceptibility to sodium lauryl sulphate (SLS)-induced irritant dermatitis was evaluated by the application of a single 24-h SLS patch test to the upper arm. Transepidermal water loss (TEWL) was measured by an evaporimeter, skin thickness by ultrasound A-scan, blood flow by laser-Doppler flowmetry and skin colour by a chroma meter using the L*a*b* system of the Commission Internationale de l'Eclairage (CIE). No difference in basal TEWL values was found between patients and controls. A decreased skin thickness was found in those with hand eczema as compared to the controls. The hand eczema patients had significantly increased L* and decreased b*-values compared to controls, indicating a more 'fair' skin. Susceptibility to SLS was increased only in patients with acute eczema, indicating that the presence of an active eczema increases the reactivity to irritants of distant uninvolved skin.

Acute Disease↗

LEKTI demonstrable by immunohistochemistry of the skin: a potential diagnostic skin test for Netherton syndrome.

BACKGROUND: Netherton syndrome (NS) is a rare autosomal recessive condition characterized by ichthyosiform erythroderma, trichorrhexis invaginata and atopic manifestations. Confirming the diagnosis may be difficult in the early stages. Mutations in the SPINK5 gene which encodes for the serine protease inhibitor LEKTI are associated with NS. These mutations create premature termination codons which result in absent or abnormal expression of LEKTI in patients with NS. OBJECTIVES: To investigate the expression of LEKTI in the skin of patients with NS in comparison with normal controls and patients with other skin conditions, namely atopic dermatitis, psoriasis and nonbullous ichthyosiform erythroderma. METHODS: Immunohistochemistry was performed on skin sections from four patients with NS, four normal controls, four with atopic dermatitis, two with psoriasis and two with nonbullous ichthyosiform erythroderma, using a primary rabbit polyclonal antibody against LEKTI. RESULTS: LEKTI was localized to the stratum granulosum in normal skin. All four skin sections from patients with NS showed absent or very reduced staining for LEKTI. Staining in the other disorders showed positive LEKTI expression in varying patterns. CONCLUSIONS: NS can be difficult to diagnose especially in the early stage, which can lead to inappropriate treatments particularly if it is misdiagnosed as atopic dermatitis. Immunohistochemistry of skin with an antibody against LEKTI is a potentially useful diagnostic test for NS.

Adolescent↗

Xeroderma pigmentosum variant: DNA ploidy analysis of various skin tumors and normal-appearing skin in a patient.

BACKGROUND: The patient with xeroderma pigmentosum provides an appropriate human model for the evaluation of tumor development and progression. METHODS: We describe a patient with variant-type xeroderma pigmentosum who developed actinic keratoses, a squamous cell carcinoma, and its metastasis into a lymph node. DNA ploidy was measured and analyzed in cells of these tumors and the patient's sun-exposed as well as sun-shielded skin. RESULTS: The sun-shielded skin showed a normal diploid DNA distribution pattern, while the sun-exposed skin had an increased number of hyperdiploid cells. The actinic keratosis showed further increased hyperdiploid cells. The squamous cell carcinoma showed a large number of hyperdiploid cells and formed an aneuploid cell fraction. Histographically, the aneuploid cell fraction became more apparent and was revealed to be a major fraction in the metastatic squamous cell carcinoma. CONCLUSIONS: The changes in the DNA ploidy pattern well reflect the clinical and histologic characteristics of the respective skin conditions and likely provide the cellular basis for the sequential or stepwise carcinogenic process in the patient's xeroderma pigmentosum skin. Further studies are necessary to determine whether the present results explain the similar carcinogenic process in sun-damaged skin of the nonpredisposed general population.

Aneuploidy↗

Diagnosis and immunotherapy of mould allergy. II. Reproducibility and relationship between skin sensitivity estimated by end-point titration and histamine equivalent reaction using skin prick test and intradermal test.

To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Reproducibility of skin sensitivity using a quantitative skin prick test.

The reproducibility of repeated quantitative skin prick test titrations was evaluated in seven asthmatic patients tested 2-4 times within 6 weeks. The skin sensitivity was estimated as endpoint titration and histamine equivalent reaction using both 1 and 10 mg/ml histamine dihydrochloride. The histamine equivalent reaction had a significantly higher reproducibility compared to endpoint titration, with a coefficient of variation less than 10% for histamine 10 mg/ml. Further, using this histamine concentration, the deviation in repeated testing was for practical purposes less than 0.5 log step. The same constancy in skin sensitivity was found in one patient tested 3 times and then retested another 3 times 6 months later by a different tester. The results indicate that the quantitative skin prick test and histamine-estimated skin sensitivity have a clinical application in the assessment of pharmacologically or immunotherapy-induced changes in the releasability of skin mast cells.

Adult↗

Type III allergy skin testing. Position statement for EAACI Subcommittee on Skin Tests and Allergen Standardization.

Immune-complex-mediated hypersensitivity has been implicated in a small number of allergic respiratory conditions. These include EAA and ABPA. In addition, there is some evidence of type IV hypersensitivity in EAA and BFL, together with activation of complement via the alternative pathway (4, 8, 26). Positive immediate skin tests are now usually regarded as an essential criterion for the diagnosis of ABPA. These reflect the presence of antigen-specific IgE, but this test is not specific for ABPA, as other atopic subjects may also be sensitized to A. fumigatus without any evidence of the parenchymal features that are required to diagnose ABPA. For FL, skin tests with currently available antigens show poor discrimination between affected patients and exposed but healthy individuals. There is little evidence that vascular deposition of immune complexes in the skin contributes to the delayed skin responses in EAA, and skin tests in FL are not specific for type III hypersensitivity. Further refinement of methodology and antigen extracts may improve the specificity of skin tests in FL, but in many cases the aetiology of EAA is multifactorial and the true causative antigens may not have been identified. Therefore, the diagnosis of EAA remains based on history and clinical findings, supported by the presence of precipitins, and sometimes by bronchial biopsy and lavage appearances (25).

Allergens↗

Maryborough skin health survey: prevalence and sources of advice for skin conditions.

A computer-assisted telephone interview survey was carried out in the City of Maryborough to determine the prevalence and sources of advice for self-reported skin conditions. Of the 443 adults contacted, 416 (94%) agreed to participate in the study. One hundred and fourteen people (27%) reported having one or more skin conditions over the past 2 weeks, which included eczema/dermatitis 25.5% (range, 18.1-32.8%; 95% CI), warts 16.1% (9.8-22.4%), acne 16.2% (9.6-22.7%), cold sores 13.1% (7.3-18.9%) and tinea 11.2% (5.9-16.5%). Medical practitioners were the most common source of advice for 49% of skin conditions, followed by family and friends or self-prescribed (25%). Advice from a pharmacist was sought for 19% of skin conditions. Logistic regression analysis showed that those people who reported a moderate to severe inflammatory skin condition, such as dermatitis, urticaria or psoriasis, were most likely to seek advice from their medical practitioner. The type and severity of skin condition were factors which determined where a person sought advice on diagnosis and management.

Adult↗

Molecular identification of the skin transformation center of anuran larval skin using genes of Rana adult keratin (RAK) and SPARC as probes.

Anuran larval skin undergoes a process of metamorphosis into pre-adult and adult skin. Basal skein, larval basal and adult basal cells are basement membrane-attaching cells in the larval, pre-adult and adult epidermis, respectively, and are identified as cells expressing genes of RLK (Rana larval keratin), both RLK and RAK (Rana adult keratin), and RAK. Larval to pre-adult skin conversion takes place in the histological entity called the skin transformation center (STC). The present study performed a cDNA subtractive gene screening on cDNA of the larval and the pre-adult skin, and cloned the secreted protein acidic and rich in cysteine (SPARC) gene as an upregulated gene in the larva to pre-adult skin conversion. RAK gene-positive basal skein cells and fibroblasts in and around the STC were weakly and strongly sparc-positive, respectively. Using sparc and rak, we redefined the STC and visualized it on a histological section as an approximately 150 microm-long region that contained about 20 rak-negative and weakly sparc-positive basal cells. Intense sparc expression was observed in basal skein cells, but not in larval basal cells, suggesting that SPARC acts as a suppressor of rak during epidermal differentiation. This suggestion was tested by investigating the effect of SPARC on cultured larval basal cells. We observed that SPARC suppressed the expression of rak, but not rlk.

Amino Acid Sequence↗