[Problems, responsibility and goals in dermatopathology].
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Diagnosis, Differential↗
Biomedical subjects
H H Wolff
Publications and source records attributed to H H Wolff.
SLS-irritated human skin shows no correlation between degree of proliferation and TEWL increase.
It is well known that cutaneous irritants influence epidermal proliferation but the pathogenesis is poorly understood. Recent investigations have shown that the skin barrier integrity influences the proliferation of the basal keratinocytes. Our question was whether the proliferating activity of keratinocytes is indeed regulated by the degree of skin barrier damage or by a direct toxic action of the irritant on the keratinocytes. Therefore various degrees of skin irritation were induced by the application of 0.1%, 0.5% and 2% sodium lauryl sulphate (SLS) solution to the forearm skin of six healthy volunteers. This experiment was performed to evaluate the relationship between SLS concentration and epidermal proliferation. In a second experiment another 14 volunteers were treated with a single SLS concentration (0.5%) to look for interindividual differences in the patterns of skin reaction and susceptibility to the irritant. Skin barrier function was evaluated by measurements of transepidermal water loss (TEWL) before and after irritation. Punch biopsies were taken after 96 h from exposed areas and from unexposed normal skin. Dividing keratinocytes were identified immunocytochemically using three different monoclonal antibodies: PCNA, MIB 1 and KiS1. Exposure to SLS resulted in concentration-dependent increases in both TEWL and epidermal proliferation. However, no significant correlation could be found between the degree of hyperproliferation and the TEWL changes. The results suggest that epidermal proliferation is modulated by a direct interaction of the surfactant with the keratinocytes and/or by release of mediators rather than the consequence of a barrier disturbance.
Adult↗
Tropical rat mite dermatitis: case report and review.
Six medical students inhabiting a centuries-old, rat-infested house in Lübeck, in northern Germany, were suffering from itching papules and seropapules. Prior to these patients' visit to our institute, their conditions had been diagnosed as pediculosis, scabies, or pulicosis and treated unsuccessfully with the antiparasitic agent lindane (0.3%). The final diagnosis, tropical rat mite dermatitis, was based on the identification of the arthropod Ornithonyssus bacoti, which has an unsegmented body with eight legs. No treatment was recommended, and the dermatitis disappeared within 2 weeks. Measures taken to prevent reinfestation included extermination of the rats and treatment of the rooms of the house with the acaricide benzyl benzoate. Because the mite O. bacoti spends a relatively short time on a host and penetrates the skin for feeding only, the application of an antiparasitic agent is not necessary. If indicated, treatment should be symptomatic.
Adult↗
Image analysis and pattern recognition for computer supported skin tumor diagnosis.
A new approach to computer supported recognition of melanoma and naevocytic naevi based on high resolution skin surface profiles is presented. Profiles are generated by sampling an area of 4 x 4 mm2 at a resolution of 125 sample points per mm with a laser profilometer at a vertical resolution of 0.1 micron. With image analysis algorithms Haralick's texture parameters, Fourier features and features based on fractal analysis are extracted. Genetic algorithms are employed successfully to select good feature subsets for the following classification process. As quality measure for feature subsets, the error rate of the nearest neighbor classifier estimated with the leaving-one-out method is used. Classification is performed with feed forward back-propagation network and the nearest neighbor classifier. Classification performance of the neural classifier is optimized using different topologies, learning parameters and pruning algorithms. The best neural classifier achieved an error rate of 4.5% and was found after network pruning. The best result with an error rate of 2.3% was obtained with the nearest neighbor classifier.
Algorithms↗
A three-step procedure for the purification of human basophils from buffy coat blood.
OBJECTIVE AND DESIGN: We report a method for basophil purification from buffy coats, which avoids positive selection of the cells and gives rise to good purity, yield and functional integrity of the cells. SUBJECTS: Buffy coat blood (concentrated leukocyte fraction derived from 450 ml venipuncture donations) obtained from healthy blood donors (n = 51). METHODS: Basophils were enriched by a three-step process starting with Ficoll density centrifugation (1.6 +/- 0.1% basophil purity) followed by counter current centrifugal elutriation (17.7 +/- 1.4% basophil purity). The final stage involved negative selection using Dynal immunomagnetic beads directed against CD2, CD14, CD16 and CD19 positive cell contaminants. Functional integrity of which was assessed by comparing the anti-IgE or calcium ionophore A23187 induced histamine release from basophils obtained from each enrichment step. Furthermore, basophil morphology was investigated using light and electron microscopy. RESULTS: The final mean basophil purity of 67.3 +/- 1.4% with a yield of 3.5 +/- 0.5 x 10(6) basophils and a recovery of 21.8 +/- 2.4% was achieved. Net histamine release from basophils stimulated with optimal concentrations of anti-human IgE was 39.1 +/- 6.5% after Ficoll centrifugation, 41.6 +/- 7.7% following elutriation and 35.7 +/- 6.8% from the final purified fraction. Additionally, basophils enriched with our method showed intact morphology by electron microscopy and were functionally active to non-immunological stimulation. CONCLUSIONS: These results compare favourably with previous studies, which have often required the use of positive selection via the Fc epsilon RI receptor, which may result in cell degranulation, or cell sorting, which cannot be applied to large cell numbers. Our method provides a reproducible technique for basophil enrichment when large numbers of functionally intact basophils are required.
Antigen-Antibody Reactions↗
[Combined naevus flammeus and naevus fuscocoeruleus: phacomatosis pigmentovascularis type IIa].
The association of nevus flammeus with mongolian spot, nevus fuscoceruleus, nevus spilus and, with variable frequency, with nevus anemicus has been termed phacomatosis pigmentovascularis, a genodermatosis first described by Ota and co-workers. Four different combinations have been specified. Most cases are reported from the Japanese literature. Phacomatosis pigmentovascularis may constitute an exclusively cutaneous disorder, but overlapping with other syndromes like Klippel-Trenaunay syndrome or Sturge-Weber syndrome is also possible. We report a 30-year-old woman with nevus flammeus on the back and right arm associated with nevus fuscoceruleus on the back.
Adult↗
[Standards in histopathologic diagnosis of malignant melanomas. Recommendations of the Working Group of the Central Malignant Melanoma Registry of the German Dermatologic Society].
The evaluation of melanocytic tumors represents one of the most intriguing and challenging aspects of the daily practice in dermatohistopathology. For the diagnosis of malignant melanoma and melanocytic nevi, standardized and reproducible criteria are required. In case of the diagnosis of melanoma, the histopathological report must include all important data relevant for the prognosis which may also influence the therapeutic procedure. The following paper summarizes the recommendations of the study group on malignant melanoma formed by the Deutsche Dermatologische Gesellschaft.
Biomarkers, Tumor↗
Adhesion molecule expression in normal skin and melanocytic lesions. Role of UV-irradiation and architectural characteristics in nevi.
Cell adhesion between surfaces of cells and to extracellular matrices represents a fundamental mechanism in tissue organization and influences the biological behaviour and the architecture of tumors. We investigated the expression of various adhesion molecules in normal skin (n=5), nevi (n=29), and malignant melanoma (n=10) by immunohistochemistry. Special attention was paid to the correlation between adhesion molecule expression and the respective architectural features, e.g. UV-induced morphological changes, and the arrangement of melanocytes in congenital nevi. In nevi, a single erythemagenic dose of UV-light did not influence the integrin expression of melanocytes, but results in an upregulation of alpha3 beta1- and alpha6 beta1-integrin within the suprabasal layers of the epidermis. This suprabasal labelling was associated with an increased number of suprabasal melanocytes in UV-irradiated nevi which were detected with HMB-45 antibody. Nine of 10 congenital nevi demonstrated a labelling of alpha4 beta1-integrin only in melanocytes of the deeper dermis. This integrin previously has been associated with high tumor thickness and the clinical outcome in melanomas. The integrin profile observed in melanomas differed in part from that seen in nevi with expression of beta2- and beta3-integrins in some cases. The results may indicate a correlation between adhesion molecule expression and histopathological findings in melanocytic lesions.
Cell Adhesion Molecules↗
Relationship between basophil chemotaxis and histamine releasability to immunological stimulation.
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Antibodies↗
Purified human peripheral blood basophils release interleukin-13 and preformed interleukin-4 following immunological activation.
Recent studies have shown that human basophils, like mast cells, generate interleukin (IL)-4 following immunological activation and may thus participate in late-phase allergic and inflammatory processes. Here, we report the capacity of human basophils to release IL-13 within 24 h following stimulation with anti-IgE. Additionally, in 14 out of 31 experiments, we observed that basophils rapidly release performed IL-4 within 5-10 min, as well as newly generated IL-4, which was released 4 h following stimulation of the cells with anti-IgE. In contrast to the biphasic release of IL-4 from the cells, no preformed IL-13 was detected at earlier times (5-30 min). Preformed IL-4 and IL-4 and IL-13 generated de novo were also released after stimulation of the cells with IL-3; an enhanced production of these cytokines was observed using a combination of IL-3 and anti-IgE. We conclude from these data that, by releasing performed IL-4 and IL-4 and IL-13 generated de novo, human basophils may be centrally involved in the orchestration of allergic inflammation by providing a trigger to IL-4-mediated T helper 2 lymphocyte activation, B cell IgE switching, and increased vascular adhesion molecule expression.
Antibodies, Anti-Idiotypic↗
Effects of basophil-priming and stimulating cytokines on histamine release from isolated human skin mast cells.
Cell priming and stimulation of different cytokines (which include chemokines and growth factors) are typical features of human basophils. Recently, it has been shown that the macrophage chemotactic protein-1 (MCP-1), RANTES and macrophage inflammatory protein-1 alpha (MIP-1 alpha) are potent direct secretagogues for human basophils and that interleukin-3 (IL-3), IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF) are priming factors for subsequent potentiation of mediator release from basophils induced by different stimuli. This observation may be clinically important for the activation and recruitment of inflammatory cells in different immune responses of the skin (e.g. late-phase reactions). The aim of the present study was to investigate whether cytokines and chemokines are also capable of priming or stimulating isolated human skin mast cells (SMC). SMC were either stimulated directly with the cytokines alone or preincubated with these factors for 10 min before being activated with suboptimal concentrations of anti-IgE, A23187 or substance P. IL-3, IL-5, GM-CSF, platelet factor-4 (PF-4), IL-8, MCP-1 and MIP-1 alpha (each at concentrations of 1 ng/ml to 1 microgram/ml, log steps) did not significantly modulate histamine release from SMC induced by the three different secretagogues. RANTES exhibited a weak but significant potentiating effect on IgE-mediated activation. Stem cell factor (SCF) as a positive control was able to prime mast cell histamine release strongly. In addition, PF-4, MCP-1, RANTES and MIP-1 alpha were incapable of inducing direct histamine release from SMC. In experiments with isolated human peripheral basophils, however, we observed potent Fc epsilon RI-mediated priming effects evoked through IL-3, IL-5 and GM-CSF. We conclude that SMC derived from healthy donors are not targets of (immuno)modulatory factors that prime or stimulate basophils.
Basophils↗
[Activation of epidermal melanocytes is independent of epithelial proliferation and vascularization. Immunohistologic study using HMB-45 antibody with review of the literature].
Antibodies against HMB-45 antigen are widely used in the immunohistochemical investigation of melanocytic tumours as a marker of activation. While malignant transformation is one explanation for HMB-45 expression, we searched for other factors by investigating 252 biopsies of non-melanocytic skin lesions with 21 different diagnoses for the presence of HMB-45, using both single and double staining techniques. Epidermal melanocytes in lesions with an increased epithelial proliferation-either neoplastic or reactive-and lesions with a prominent vasculature showed an enhanced expression of HMB-45. The results indicate that the presence of HMB-45 is not only influenced by primary melanocytic changes but also may be dependent on epithelial proliferation and vascular factors. These mechanisms should be considered when interpreting HMB-45 staining of melanocytic lesions.
Antigens, Neoplasm↗
Altered x-ray diffraction pattern is accompanied by a change in the mode of cross-link formation in lipodermatosclerosis.
We studied the molecular packing of collagen fibrils by x-ray diffraction in skin specimens of patients with lipodermatosclerosis and in controls. A difference in the tilt angles of the collagen molecules relative to the fiber axis is suggested by a D-stagger that is 1 nm larger in sclerotic skin than in normal skin. In parallel, the collagen cross-links in the skin specimens were analyzed, and a marked increase of both hydroxylysylpyridinoline and lysylpyridinoline, the trivalent mature cross-links characteristic of skeletal tissues, was found. The content of hydroxylysylpyridinoline and lysylpyridinoline was higher in the deep layer of the affected dermis than in the superficial dermis. This increase was always accompanied by an increase in the hydroxylysylpyridinoline/lysylpyridinoline ratio, suggesting that hydroxylysylpyridinoline is a sclerosis-associated cross-link. In addition, lysyl hydroxylation was increased in affected skin, and this increase was apparently restricted to the collagen telopeptides, which are crucial anchoring structures for lysyl dependent cross-links.
Amino Acids↗
Skin permeability barrier and occlusion: no delay of repair in irritated human skin.
It has been reported that occlusive treatment of irritated skin results in a reduction of barrier repair activities in hairless mice. In contrast, the clinically observed benefit of occlusion in the treatment of hand eczema and other chronic skin diseases with a perturbed barrier function is well-known. While the beneficial effect of occlusion has been proven for the treatment of psoriasis there are no controlled clinical studies of the effect of occlusion on irritated human skin. We have therefore evaluated the effect of various occlusive treatments on repair of the human skin permeability barrier under controlled experimental conditions. Barrier perturbation was induced either by application of sodium lauryl sulfate (SLS) or by repeated tape stripping. This was followed by treatment with different occlusive and semipermeable dressings, partly after pre-treatment with petrolatum. Repair of water barrier function was evaluated by daily measurements of transepidermal water loss (TEWL) for 1 week. SLS irritation and tape stripping led to a 6-fold increase in TEWL as a sign of severe water barrier perturbation, followed by a stepwise decrease over the following days. Occlusion did not significantly delay barrier repair as measured by TEWL. Only in tape-stripped skin did TEWL stay at high levels during treatment with self-adhesive dressings. This may be explained by damage of newly formed stratum corneum caused by changing of these membranes. Our results indicate that, in contrast to earlier observations in hairless mouse skin, permeability barrier repair activities are not significantly delayed by occlusive treatment in human skin.
Adult↗
Heterogeneity of human skin mast cells and human basophils. I. Pharmacological experiments with activators and inhibitors of protein kinase C.
Skin mast cells and basophilic leukocytes are known as key elements of acute and subacute IgE-mediated immune responses of the skin. The present paper investigated pharmacological aspects of signal transduction pathways of both cell types using activators and inhibitors of protein kinase C (PKC). The nonselective inhibitor K252a suppressed Fc epsilon RI-mediated histamine release from basophils and skin mast cells dose-dependently with IC50 values of 0.01 and 0.28 mumol/l. However, preincubation of both cell populations with kinase inhibitors showing in vitro selectivity for PKC (Ro 31-7549, calphostin C, GF 109203X) revealed a distinct modulation of cell response: IgE-mediated mediator release was inhibited only in skin mast cells, whereas in experiments with basophils a concentration-dependent potentiation of exocytosis was observed. Further evidence for heterogenous biochemical signals following activation of both cell types derived from studies with the phorbol ester TPA. With respect to acute and late-phase IgE-mediated skin reactions, we suggest that distinct signal transduction mechanisms at the level of PKC (isozymes) in basophils and skin mast cells might reflect their functional heterogeneity.
Animals↗
Proliferative activity of keratinocytes correlates with that of melanocytes in naevi and melanomas.
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Cell Division↗
[Bacillary angiomatosis].
Bacillary angiomatosis (BA) is a rare infectious disease usually associated with HIV infection. Recent molecular biologic investigations confirm that both Rochalimaea henselae and Rochalimaea quintana can cause BA. The bacteria can be identified by Warthin-Starry staining and electron microscopy. The typical clinical signs are solitary or multiple dermal or subcutaneous nodules. Bone, liver, spleen and other organs may also be involved. We describe the clinical and histological features of a 39-year-old HIV-infected patient with cutaneous and bony lesions of BA. All manifestations of BA disappeared during therapy with erythromycin.
AIDS-Related Opportunistic Infections↗
[The role of basophilic leukocytes in inflammatory skin diseases].
Basophilic leukocytes are effector cells of the peripheral blood. They have several morphological and functional characteristics in common with tissue mast cells, such as expression of the high-affinity IgE receptor (Fc epsilon RI) and a high content of histamine within their granules. Functional comparison of human basophils and human mast cells isolated from different tissues revealed marked heterogeneity of mediator release after incubation with different secretagogues. Owing to their wide range of surface receptors, their (pro)inflammatory mediators released after activation, their mobility, and their rapid turnover, basophils appear basically to be potent effector cells, which migrate transiently into the skin during IgE-mediated (and/or IgE-independent) inflammatory reactions. The present paper reviews recent findings on the possible role of basophils for different immune reactions of the skin. Inhibition of basophil (and/or mast cell) activity seems to be necessary for both effective prophylaxis and therapy of allergic and inflammatory skin diseases. To date, however, the pharmacological modulation of mediator release from basophils lacks potent clinically useful compounds that can suppress the cellular response, since mast cell stabilizers such as cromoglycate and nedocromil are not effective. With a view to the development of active compounds, further in vitro studies should focus on the mechanisms of cell activation.
Basophils↗