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Wolfram Sterry

Publications and source records attributed to Wolfram Sterry.

At least 91 records · Page 5Linked to original sources
PubMed2003

[Topical immunomodulators for treatment of eczema].

Anti-inflammatory treatment of eczematous skin diseases like atopic dermatitis and allergic contact dermatitis has mainly been performed with topical glucocorticosteroids. Increasing knowledge of the pathophysiological interactions and the immunological mechanisms during the chronic inflammatory processes in the skin offers new therapeutical options. In this review, new therapeutical approaches for the treatment of eczematous skin disease will be presented. These novel compounds include the topical immunomodulators, tacrolimus and pimecrolimus. Such molecules inhibit intracellular signal transducing phosphatases and act consecutively at the molecular level by inhibiting the activation of transcription factors. Secondly, the development of nuclear hormone receptor family members, such as retinoids, vitamin D and peroxisome proliferator-activated receptor agonists, is discussed. Substances from this family have differentiating, antiproliferative, but also immuno-modulatory effects, which make them attractive as anti-eczematous therapeutic compounds. The diversity of these interactions is extensive, and clinical studies will prove their clinical efficacy.

Adjuvants, Immunologic↗
PubMed2003

Effect of the vehicle on the amount of stratum corneum removed by tape stripping.

BACKGROUND: The penetration of topically applied substances into the stratum corneum can non-invasively be studied using the tape stripping procedure. This method was applied to investigate in vivo the penetration of a fragrance, vanillin, applied in ethanol and a w/o emulsion. METHODS: Twenty tape strips were removed from each skin area treated with vanillin in ethanol or w/o emulsion, respectively. The concentration of vanillin was determined for each tape strip. In addition, the pseudo-absorption of the corneocytes was determined to calculate the SC profile. RESULTS: The vanillin concentration was correlated both with the tape number and with the stratum corneum profile. Depending on whether the tape number or the profile of the stratum corneum were correlated with the vanillin concentration, different distributions within the stratum corneum were obtained. Different amounts of stratum corneum were removed with 20 tape strips dependent on the vehicle applied previously. The application of the w/o emulsion led to the removal of nearly the half the amount of corneocytes stripped from the ethanol-treated area. CONCLUSIONS: The results obtained underline the general necessity to correlate the amount of stratum corneum with the amount of substance in penetration studies.

Administration, Topical↗
PubMed2003

T cell receptor-gamma gene analysis of CD30+ large atypical individual cells in CD30+ large primary cutaneous T cell lymphomas.

The hallmark of primary cutaneous CD30+ large T cell lymphoma are large lymphoid tumor cells, at least 75% of which, by definition, must be positive for CD30. The relatively benign clinical course of this lymphoma type has been explained with CD30-induced apoptosis, on the assumption that expression of CD30 defines the tumor clone; however, this hypothesis has not been tested on the molecular level to date. In this study we analyzed CD30+ cells in four patients with primary cutaneous CD30+ large T cell lymphoma by single cell polymerase chain reaction of T cell receptor-gamma genes followed by sequencing. Here, we demonstrate that most of the large CD30+ atypical cells possessed identical T cell receptor-gamma gene rearrangements, indicative of clonal proliferation. Nevertheless, polyclonally rearranged T cells were present in all CD30+ samples studied. In addition, one patient showed a second clone in a separate biopsy and three of four patients showed chromosomal imbalances as revealed by comparative genomic hybridization. Taken together, our data suggest that the CD30+ population in primary cutaneous CD30+ large T cell lymphoma indeed contains the tumor clone, thus providing molecular support for a link between clinical course and CD30-related signaling. Importantly, however, CD30 expression does not define the tumor clone as bystander T cells, as well as occasional additional clones, are also present in this population.

Adult↗
PubMed2003

Ultraviolet B radiation-mediated inhibition of interferon-gamma-induced keratinocyte activation is independent of interleukin-10 and other soluble mediators but associated with enhanced intracellular suppressors of cytokine-signaling expression.

Ultraviolet irradiation represents a well-established treatment modality for inflammatory skin diseases. The aim of this study was to investigate the mechanisms of ultraviolet B radiation-induced keratinocyte insensitivity towards interferon-gamma. Flow cytometric analyses indicated that ultraviolet B radiation temporarily inhibits the interferon-gamma-induced activation of primary keratinocyte and HaCaT cells as measured by reduced intercellular adhesion molecule-1 (CD54) and HLA-DR upregulation. Western blot experiments have suggested that this is mediated by the ultraviolet B radiation-induced inhibition of signal transduction and transcription factor-1 phosphorylation. Neither interleukin-10 neutralization nor interleukin-10 addition had any effect on the ultraviolet B radiation-induced inhibition of interferon-gamma induced intercellular adhesion molecule-1 expression. Furthermore, the supernatant from ultraviolet B-irradiated cells failed to inhibit the interferon-gamma-induced CD54 and HLA-DR upregulation in nonradiated HaCaT cells. Moreover, irradiated cells from whom the supernatant was withdrawn 4 h after irradiation still showed a diminished interferon-gamma-induced response after 24 h. Thus, not soluble but intracellular factors might be involved in the ultraviolet B radiation-induced inhibition of interferon-gamma-induced keratinocyte activation. Therefore, we analyzed the expression of members of suppressors of cytokine-signaling (SOCS) molecules using real-time polymerase chain reaction. We found a fast and strong upregulation of SOCS1 and SOCS3 but not of SOCS2 after ultraviolet B radiation. Similarly, ultraviolet B radiation induced the expression of these particular SOCS molecules in lesional psoriatic skin. As SOCS molecules are known inhibitors of signal transduction and transcription factor phosphorylation, which is essential for interferon-gamma-induced intercellular adhesion molecule-1 and HLA-DR upregulation, this may explain the interferon-gamma unresponsiveness after ultraviolet B radiation.

Adjuvants, Immunologic↗
PubMed2003

Chemokine receptor expression on neoplastic and reactive T cells in the skin at different stages of mycosis fungoides.

We analyzed the expression of 13 chemokine receptors in mycosis fungoides, in order to assess the contribution of chemotaxis to the pathogenesis of the disease. Material from skin biopsies of six patients with early disease and six patients at the tumor stage of mycosis fungoides was analyzed by immunohistochemistry and partly also by flow cytometry. The receptors CCR1, CCR2, CCR3, CCR5, CCR6, CXCR1, CXCR2, CXCR5, and CX3CR1 were rarely and inconsistently detected in lesional skin and thus their participation in mycosis fungoides could largely be ruled out. In contrast, CCR4, CXCR3, and CXCR4 were substantially expressed on both mycosis fungoides cells and the surrounding reactive T cells in the early patch and plaque stages of the disease, indicating an involvement of these chemokine receptors in the disease process. In the tumor stage of mycosis fungoides, we interestingly observed a loss of a relevant chemokine receptor in four out of six patients. In three patients CXCR3 and in one patient CCR4 was absent on tumor mycosis fungoides cells, whereas the reactive T cells showed normal levels of expression. Within these samples, tumor mycosis fungoides cells exhibited high levels of CCR7, a chemokine receptor central for the entry of T cells to lymphatic tissue. Taken together, our data suggest that the loss of one or more of the chemokine receptors involved in the homing of the mycosis fungoides cells to the skin may trigger the latent potential of these cells to metastasize into regional lymphatic tissue.

Adult↗
PubMed2003

Intradermal injection of Newcastle disease virus-modified autologous melanoma cell lysate and interleukin-2 for adjuvant treatment of melanoma patients with resectable stage III disease.

BACKGROUND: The value of active specific immunotherapy (ASI) for the treatment of solid tumours still has to be assessed. The objective was to test an autologous tumour cell vaccine for adjuvant treatment of stage III melanoma patients. PATIENTS AND METHODS: After open vaccination of 12 patients, another 17 patients were recruited for a randomized double-blind trial comparing treatment with the vaccine (n = 9) and with a placebo (n = 8). Intracutaneous vaccinations were given postoperatively in weeks 2, 4, 6, 12, 24 and thereafter every 6 months if sufficient vaccine material was available. Patients were followed for 60-84 months. RESULTS: Median disease-free survival time was 5 months for open-treated, 4 months for verum-treated and 6 months for placebo-treated patients. Corresponding median overall survival times were 30.5, 18 and 18.5 months, respectively. There were no remarkable differences between the verum and the placebo group. CONCLUSIONS: Adjuvant treatment of melanoma patients with an autologous ASI vaccine did not show clinical efficacy in this cohort of melanoma patients.

Adolescent↗
PubMed2003

[Dithranol in the treatment of scalp psoriasis].

Dithranol in its usual petrolatum base cannot be effectively applied to the scalp. The washable cream base is not often employed in Germany, both because this form of application is not well-known and because the positive effects are underestimated while the adverse effects are overestimated. Therefore we have searched the literature for appropriate studies, application recommendations and reports on side effects. We list scalp preparations containing dithranol available in neighbouring European countries together with recommendations and warning notes. Since the dithranol molecule contains hydrophilic and lipophilic parts, it can be easily incorporated into soaps. The stability of such preparations is limited; their effectiveness is supported by the usage of dithranol in an emulsifying oil base in the Charité Department of Dermatology for more than twenty years. The special vehicle used, bio-wash-oil, is an oily fluid soap which was designed for cleaning the heavily soiled hands of factory workers. It can be easily applied to the scalp and washed off with water. Here we re-examine the original study on dithranol in bio-wash-oil published by Meffert et al. in 1979, summarize our subsequent experience and present a recent comparative study paying special attention to side effects, practical notes, and patient comfort and satisfaction.

Anthralin↗
PubMed2003

[New developments in the systemic treatment of psoriasis].

The current standard systemic therapeutic modalities for psoriasis have many potential side effects. Progress made in the understanding of the pathophysiology of psoriasis as a T-cell-mediated dermatosis provide options for new more precise therapeutic approaches. These immunological therapeutic strategies involve the inhibition/depletion of activated T-lymphocytes, the inhibition of antigen presentation and thus the regulation of T-cell activation, the inhibition of adhesion of inflammatory cells, the inhibition of effects of proinflammatory mediators and the administration of antiinflammatory cytokines. This article summarizes these new systemic therapeutic approaches. Clinical results in the early studies have been mixed. In the next years further results of phase II- and phase Ill-studies may be expected, which should allow better assessment of the potential of those particular approaches. Some of these approaches could lead to the approval of new drugs to treat psoriasis and to enhance or replace already existing therapeutic options. Furthermore results of therapeutic experiments should contribute to a better understanding of the disease. As we learn which mechanisms are more or less important for the disease, we will be better able to plan intervention strategies.

Anti-Inflammatory Agents↗
PubMed2003

CD4+ CD56+ neoplasia: clinical and biological features with emphasis on cytotoxic drug-induced apoptosis and expression of sialyl Lewis X.

CD4+ CD56+ neoplasia is a rare malignancy of unclarified origin. So far only 57 cases have been reported. We characterized in detail a case of CD4+ CD56+ malignancy with special emphasis on apoptosis induced by cytotoxic drugs and expression of sialyl Lewis X (CD15s). The disease was diagnosed in a 73-year-old female presenting with skin involvement, generalized lymphadenopathy and bone marrow infiltration. Treatment with cladribine/mitoxantrone induced a short-lasting partial response and the patient died 6 months after diagnosis. The neoplastic cells expressed CD4, CD56, HLA-DR, and CD15s. PCR for the T-cell receptor gamma chain revealed a polyclonal amplification product. In situ hybridization for Epstein-Barr Virus (EBV) was negative. Cytotoxic granule-associated proteins were not detected, consistent with the observation that the cells did not mediate cytotoxic activity against several target cells. Apoptosis of the tumor cells was inducible by anthracyclines and cladribine but not with gemcitabine. Combinations of cladribine or gemcitabine with anthracyclines however, resulted in synergistic effects on apoptosis. Expression of CD15s on the CD56+ cells was three times higher than on CD56+ cells from healthy controls. The results demonstrate that the features of the present case is in accordance with the diagnosis of CD4+ CD56+ malignancy. This is the first report demonstrating increased CD15s expression on a CD4+ CD56+ neoplasia, possibly explaining the frequent occurrence of the disease in the skin.

Aged↗
PubMed2003

Peripheral blood T-cell clonality in mycosis fungoides and nonlymphoma controls.

In mycosis fungoides (MF), T-cell clonality is reported in about 90% of skin and 40% of blood samples. However, identity of blood and cutaneous T-cell clone and prognostic relevance of blood T-cell clonality remain controversial. By PCR/fluorescence fragment analysis with estimation of clonal fragment lengths and relative peak heights, we objectively identified T-cell clonality unrelated to malignant lymphoproliferation in healthy donors (5/38), autoimmune dermatoses (3/8), and nonlymphoma skin cancer (9/39). This T-cell expansion of undetermined significance (TEXUS) was also found in 8/64 MF patients. Dissemination of neoplastic cells into blood, as identified by identical clonal fragment lengths in blood and skin, was detected in 23/64 MF patients. When monitoring for progression at TNM stage for a mean of 45.7 months, univariate analysis identified age of >60 years and detection of a related blood T-cell clone to be of prognostic relevance, whereas detection of TEXUS, sex, TNM stage at initial diagnosis, and detection of a cutaneous T-cell clone were irrelevant. Although multivariate analysis was not possible, further stratification clearly indicated an age of >60 years to be the predominating prognostic factor. In conclusion, investigation of T-cell clonality in skin and blood samples at the initial diagnosis cannot predict the clinical course of MF and the occurrence of TEXUS should be considered when assessing blood T-cell clonality.

Adult↗
PubMed2003

Quantification of the horny layer using tape stripping and microscopic techniques.

Tape stripping is a method well suited for studying the penetration of topically applied substances into the upper part of the skin, the stratum corneum (SC). The amount of topically applied substances removed by each tape strip can be determined by common analytical methods. These amounts have to be correlated with their location within the horny layer in order to determine penetration profiles. Therefore the amount of SC on each removed strip must be determined. In the study reported, this amount was derived from the covering density of the SC cells, the corneocytes, on tape strips using classic microscopic techniques and laser scanning microscopy. The amount of corneocytes determined by both microscopic methods shows a good correlation (R2 +/- S.D.= 0.95 +/- 0.02) with the pseudoabsorption of the corneocytes, a method usually used to determine the SC amount on the removed strips. These measurements require the application of a special spectrometer, whereas the covering density can easily be determined using widely available microscopic equipment. The penetration of a typical UV filter, butyl methoxydibenzoylmethane, applied at two different formulations, was studied using the microscopic method developed. The calculated penetration profiles show that the applied formulation influences the amount of corneocytes on the removed strips.

Adult↗
PubMed2003

Cytokine and anticytokine therapy in dermatology.

Cytokines play a pivotal role in the initiation, propagation and regulation of immunologic responses. They are of utmost importance in the pathogenesis of several diseases, including skin diseases. Using cytokines or cytokine antagonists as immunomodulators exhibiting either immunosuppressive or immunostimulatory effects is a rapidly emerging field and is already adding or is about to add significantly to the therapeutic arsenal for malignant and inflammatory dermatoses. Whereas some cytokine therapies, such as IFN-alpha or IL-2, are well-established in melanoma therapy, there are others in early stages of clinical development. The fascinating aspect is the ongoing transition of the work in basic immunobiology of skin diseases into clinical application. Vice versa, observations in clinical trials are also instrumental in further promoting our knowledge of the pathophysiology of skin diseases. In this review, the current status of cytokine and anticytokine therapy for skin diseases is discussed.

Animals↗
PubMed2002

Analysis of cytokine expression in dermatology.

During the past decade, the detection of cytokines has been a focus of scientific interest, including in dermatology. Dysregulation of cytokine production seems to be involved in the pathogenesis of various diseases. The determination of cytokine levels is of increasing diagnostic importance, and cytokines are used as therapeutic agents too. Cytokines are polypeptides secreted by a wide variety of cells in response to diverse stimuli, and mediate autocrine, paracrine, or endocrine effects that are often pleiotropic and redundant. Their molecular weight lies between 6 and 70 kd. The cytokines of immunologic relevance are primarily those that are formed by immune cells (monokines and lymphokines) and/or influence their function. In principle, cytokines are detectable on 3 levels: (1) By using polymerase chain reaction, the messenger RNA expression of cytokine genes can be detected and, with the newer techniques, even quantified. (2) Protein synthesis can be detected by using bioassays and enzyme immunoassays or immunocytologic or immunohistologic detection of intracellular cytokine production. (3) Finally, there are indirect methods for the detection of cytokine formation by analysis of products of cytokine activity. The immunobiological features of cytokines and the different approaches for cytokine determination are briefly discussed herein because basic knowledge of these biologically highly active messenger substances and the capabilities and limits of the individual detection methods are essential for a sensible interpretation of the relevant findings.

Biological Assay↗
PubMed2002

Novel immunotherapies for psoriasis.

New insights into the pathophysiology of psoriasis have suggested possibilities for targeted therapeutic intervention. Several novel, systemic immunomodulatory therapies are currently in clinical development and results of recent clinical trials are remarkable. These include approaches targeting antigen presentation and costimulation, T-cell activation and leukocyte adhesion, the action of proinflammatory mediators and the administration of anti-inflammatory cytokines. These trials contribute to our further understanding of the disease, indicating which mechanisms play a greater or lesser part in its development. Moreover, they will lead to new therapeutic options. If psoriasis is considered as a visible model disease for T-cell-mediated disorders characterized by a type-1 cytokine pattern these recent findings might have a more general impact on the treatment of autoimmune disorders.

Adjuvants, Immunologic↗