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T Ruzicka

Publications and source records attributed to T Ruzicka.

At least 109 records · Page 6Linked to original sources
PubMed2001

The 5-aminolevulinic acid-induced porphyrin biosynthesis in benign and malignant cells of the skin.

In fluorescence diagnosis and photodynamic therapy of neoplastic tissues 5-aminolevulinic acid is used to synthesize endogenous porphyrins as photosensitizers. The efficacy of neoplastic tissues to fluorescence diagnosis and photodynamic therapy is thought to be dependent on the total level of intralesional formed porphyrins. The available profiles of porphyrin metabolites in normal and in neoplastic cell lines after administration of 5-aminolevulinic acid vary considerably. Thus, this is the first in-vitro study which compares the porphyrin biosynthesis in normal skin cells (HaCaT, fibroblasts) with melanoma cells (Bro, SKMel-23, SKMel-28). After incubation with 1 mM 5-aminolevulinic acid, kinetics of porphyrin levels and metabolites were determined in the cells and the corresponding supernatants. Exogenous 5-aminolevulinic acid induced porphyrin formation in all cells with maximum values after an incubation period of 16-36 h. Increase of porphyrin levels varied from 10- to 80-fold (SKMel-28>HaCaT>fibroblasts>SKMel-23>>Bro) with minimum 1.5 times higher levels of porphyrins in the supernatants than in the cells. In cells and supernatants protoporphyrin and coproporphyrin were the predominantly formed porphyrin metabolites. Metastatic melanoma cells (SKMel-23, SKMel-28) accumulated much higher porphyrin levels than primary melanoma cells (Bro). In conclusion, by optimizing the treatment modalities, especially the light source, topical photodynamic therapy (PDT) could become a treatment alternative of melanoma metastases in progressive disease.

Aminolevulinic Acid↗
PubMed2001

[Malignant melanoma: epidemiological data from the Düsseldorf area].

Malignant melanoma represents only 1.5-2.5% of malignant neoplasms in Europe. Since 1990 the clinical data of melanoma patients are registered at the clinic for dermatology university Düsseldorf. 925 patients were treated between 1990-1996 (not including in situ melanomas, extracutaneous melanomas and multiple melanomas). In 1996 the incidence was 15 cases/100,000 habitants. A worldwide doubling of the morbidity is expected every ten years especially in the caucasian population.

Adolescent↗
PubMed2001

[Adjuvant therapy of malignant melanoma].

Malignant melanoma is resected with curative intent in 80-85% of the patients. In case of tumor thickness according to Breslow of > 4 mm and metastatic regional lymph nodes a high relapse rate and mortality of 50-90% is observed. Single agent chemotherapy with DTIC is effective as combination regimen, however does not significantly improve the relapse-free interval respectively the overall survival or quality of life. Several attempts with other adjuvant treatment modalities (e.g. BCG immunotherapy) are not convincing as well. The best results of adjuvant treatment in high-risk resected melanoma were published in 1996 by Kirkwood, who used interferon-alfa 2b. He could demonstrate a prolonged relapse free and overall survival. It does represent the current standard adjuvant treatment. However, the costs and toxicities of IFN are barriers to its widespread use.

BCG Vaccine↗
PubMed2001

[Rediscovery of thalidomide. Successful treatment of discoid lupus erythematosus].

Thalidomide, an oral drug introduced in Germany in 1953 as a mild sedative, was withdrawn from the world market when its teratogenic effect was discovered some years later. It has since been selectively reintroduced to treat a variety of autoimmune or inflammatory diseases such as erythema nodosum leprosum, prurigo nodularis, graft-versus-host disease, and discoid lupus erythematosus (DLE). We report on three patients with long-standing, severe DLE showing no response to systemic first-, second- and third-line treatments. After four weeks of therapy with thalidomide the skin lesions had improved dramatically and after three to six months all three patients responded with an almost complete remission. The side effects of thalidomide, especially somnolence and paresthesias, were minor and well tolerated by the patients. Our data confirm that thalidomide provides one of the most useful therapeutic alternatives for chronic refractory DLE, despite the risks of teratogenicity and polyneuropathy.

Adult↗
PubMed2001

[Differential diagnosis of leg ulcers].

Over the last years the treatment of chronic leg ulcers has developed from a merely symptomatic to a differentiated therapy. Although more than 90% of the ulcers are of vascular origin, many other causes are possible. A survey of the various triggers of chronic ulcers of the lower limb is given. Vascular, hematological, neuropathic, infectious, malignant and chemico-physical causes are discussed. New findings regarding hemostatic defects as the basis of thrombophilia and ulcers are presented.

Bacterial Infections↗
PubMed2001

Topical immunomodulators--progress towards treating inflammation, infection, and cancer.

Immunomodulators include both immunostimulatory and immunosuppressive agents. Only recently have the basic mechanisms of topical immunotherapy been elucidated. Besides topical contact sensitisers (eg, diphencyprone or dinitrochlorobenzene), newer agents of the imidazoquinoline family such as imiquimod and resiquimod act by inducing cytokine secretion from monocytes or macrophages (interferon-alpha, interleukin-12, tumour-necrosis factor-alpha). The locally generated immune milieu leads to a Th1-dominance and cell-mediated immunity that have been used clinically to treat viral infections such as human papillomavirus (HPV), herpes simplex virus (HSV), mollusca, and cancerous lesions including initial squamous cell and basal cell carcinoma in immunocompetent and immunosuppressed patients. While these agents improve antigen-presentation by dendritic cells, they also act on B cells and lead to the synthesis of antibodies such as IgG2a much like the recently discovered immunostimulatory CpG-sequences that stimulate innate immunity. These sequences act as "danger signals" since they occur in bacterial and viral DNA, but are selectively methylated and inactivated in the mammalian genome. They share the induction of the same cytokines as imidazoquinolines but they show different magnitudes and kinetics of response. Topical immunotherapy with immunostimulatory agents shows potential for effective and patient-friendly treatment of inflammatory, infectious, and cancerous skin diseases. Immunoenhancers such as imdazoquinolines and CpG-sequences also have adjuvant properties that could improve conventional (protein) and DNA vaccination against cancer, atopy, and allergies.

Adjuvants, Immunologic↗
PubMed2001

Role of integrin alphaE(CD103)beta7 for tissue-specific epidermal localization of CD8+ T lymphocytes.

Tissue-specific T cell localization is crucial for immune surveillance of normal tissues and the pathogenesis of inflammatory disorders. In psoriatic skin, CD8+ lymphocytes predominantly reside within the epidermis, whereas CD4+ T cells are most abundant within the dermis. Molecular mechanisms guiding this spatial compartmentalization are not completely understood, however. Here, we demonstrate that 55% (+/-9.7%, n = 14) of the epidermal T cells, predominantly of the CD8+ phenotype, expressed the integrin alphaE(CD103)beta7. In contrast, only 5% (+/-2.0%) of the dermal T cells were alphaE(CD103)beta7+. Integrin alphaE(CD103)beta7 was not detected in normal skin (n = 10), and less than 1% of peripheral blood lymphocytes derived from normal (n = 11) or psoriatic (n = 10) donors expressed alphaE(CD103). When cultured T lymphoblasts (n = 12 donors) were stimulated with transforming growth factor beta1, expression of integrin alphaE(CD103)beta7 was induced on 52.8% (+/-16.2%) of CD8+ cells, but only on 6.1% (+/-2.3%) of CD4+ cells, suggesting selective inducibility on CD8+ lymphocytes. Whereas similar overall expression of transforming-growth-factor-beta1-specific mRNA was detected in normal and psoriatic skin by real-time quantitative polymerase chain reaction, immunohistochemistry revealed focal overexpression of transforming growth factor beta1 underneath psoriatic, but not normal, epidermis. This heterogenous transforming growth factor beta1 expression may contribute to induction of alphaE(CD103) in vivo. Adhesion of transforming-growth-factor-beta1-stimulated CD8+, but not CD4+, T cells to cultured keratinocytes and psoriatic epidermis in frozen sections could be significantly inhibited by antibodies that blocked the alphaE(CD103)/E-cadherin interaction. Co-culture of lymphoblasts and keratinocytes resulted in marginal enhancement of alphaE(CD103)beta7 expression in some cases. Overall, integrin alphaE(CD103)beta7 appears to contribute to tissue-specific epidermal localization of CD8+ T lymphocytes.

Antigens, CD↗
PubMed2001

Botulinum toxin A in the therapy of mimic facial lines.

In aesthetic medicine, many different methods of skin rejuvenation are available. At the end of the 1980s, the neurotoxin Botulinum toxin A (BT-A) led to a revolution in aesthetic-corrective dermatology for the treatment of mimic facial wrinkles. The toxin is produced by Clostridium botulinum and causes a reversible, selective muscle relaxation that leads to a temporary flattening of the mechanical part of wrinkling without the stigmata of invasive surgery. After two decades of experience in different medical disciplines, there has been remarkable clinical development and progress in research, the identification of new botulinum toxin serotypes, and also innovation in indications and combined modalities. These lead to new and interesting questions. BT-A offers the experienced, critical dermatologist a time-saving, effective, cosmetically satisfactory, non-invasive treatment for mimic facial wrinkles and neck and decollete lines, with only minor side effects. Dermatologists should have a profound anatomical knowledge and should be able to perform all injection techniques to meet the needs of ever more demanding patients and to ensure optimization of patient satisfaction. The following review summarizes the historical development and the mechanism of action of both frequently and rarely used injection techniques with BT-A for the treatment of wrinkles and lines of the upper face, neck and décolleté, and gives an update of different experiences encountered.

Aging↗
PubMed2001

"Second hit" in sebaceous tumors from Muir-Torre patients with germline mutations in MSH2: allele loss is not the preferred mode of inactivation.

Muir-Torre syndrome is an autosomal-dominant inherited disorder predisposing to both sebaceous skin tumors and internal neoplasms. In a significant proportion of Muir-Torre syndrome patients skin tumors exhibit microsatellite instability as a hallmark of hereditary nonpolyposis colorectal cancer. Most individuals predisposed to hereditary nonpolyposis colorectal cancer harbor a germline mutation in the DNA mismatch repair genes MSH2 or MLH1. In Muir-Torre syndrome the vast majority of germline mutations have been identified in MSH2. Microsatellite instability in tumor tissue develops after somatic inactivation of the corresponding second mismatch repair allele ("second hit"). So far, the mechanisms of somatic inactivation of the second allele in microsatellite instability positive tumors from patients with known mismatch repair germline mutations are not well understood. We examined whether allele loss (loss of heterozygosity) is a frequent mechanism for inactivation of the second MSH2 allele in a sample of nine microsatellite instability positive skin tumors from eight unrelated Muir-Torre patients with known MSH2 germline mutations. Loss of heterozygosity was determined using microsatellite markers or heteroduplex analysis, respectively. Only one of the nine skin tumors exhibited loss of heterozygosity at the MSH2 locus. Thus, we could show in a sample of sebaceous tumors from patients with genetically proven Muir-Torre syndrome that loss of heterozygosity most probably is not the preferred mode of somatic inactivation of the second MSH2 allele.

Adult↗
PubMed2001

A mannose-binding receptor is expressed on human keratinocytes and mediates killing of Candida albicans.

Human keratinocytes are known to kill Candida albicans in vitro, but the mechanism of killing is not yet understood. Here, we demonstrate that spontaneous, ultraviolet-B-light-induced, alpha-melanocyte-stimulating-hormone-induced, and interleukin-8-induced Candida killing by keratinocytes can be inhibited with mannan and mannosylated bovine serum albumin (Man-BSA). A polyclonal goat serum raised against the human macrophage mannose receptor stained suprabasal keratinocytes, but no staining was observed on keratinocytes with a monoclonal antibody (mAb15) specific for the human macrophage mannose receptor. Mannose-affinity chromatography of keratinocyte extract isolated a 200 kDa protein, and on the Western blot the goat antiserum reacted with a 200 kDa protein. In radioligand binding studies, the binding of 125I-Man-BSA to human keratinocytes was inhibited by mannan in a concentration-dependent manner. Analysis of the binding revealed a single class keratinocyte mannose receptor with a KD of 1.4 x 10(-8) M and a Bmax of 1 x 10(4) binding sites per cell. The binding of 125I-Man- BSA to keratinocytes proved to be time-dependent, acid-precipitable, and Ca2+- and trypsin-sensitive. After trypsinization the receptors underwent a rapid recovery at 37 degrees C. These results demonstrate the presence of mannose receptor on human keratinocytes, and its active involvement in the killing of Candida albicans.

Antibodies, Monoclonal↗
PubMed2001

Phototesting in lupus erythematosus: a 15-year experience.

It has long been observed that sun exposure can induce or exacerbate skin lesions in patients with certain forms of lupus erythematosus. Despite the frequency of photosensitivity in these patients, the mechanism by which ultraviolet radiation alters the pathogenic course of this disease remains poorly understood. After development of standardized test methods, our group demonstrated in 1986 that skin lesions in patients with lupus erythematosus can be experimentally reproduced by UVA and UVB irradiation. In the following years, phototesting has received much attention as a valid model to study photosensitivity of different forms of lupus erythematosus and the pathogenetic mechanism of this disease. Further investigations have also made it possible to find genetic and immunologic factors associated with photosensitivity and have helped to identify the pathophysiologic steps involved in the induction of such skin lesions. We present phototesting results and clinical correlations of more than 400 patients with different forms of lupus erythematosus and discuss the recent advances in provocative phototesting.

Adolescent↗
PubMed2001

Treatment of cicatricial pemphigoid with mycophenolate mofetil as a steroid-sparing agent.

BACKGROUND: Cicatricial pemphigoid (CP) is a rare autoimmune bullous disease that affects the skin and mucous membranes. It commonly ends by serious complications such as blindness, stenosis, and stricture formation and is difficult to treat. Mycophenolate mofetil has been reported to be effective in the treatment of pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid either as monotherapy or as a steroid-sparing agent. OBJECTIVE: Our purpose was to evaluate the effectiveness of mycophenolate mofetil as a steroid-sparing agent in treating patients with CP. METHODS: Three patients with CP were treated with mycophenolate mofetil and prednisolone. RESULTS: All 3 patients responded very well to the therapy. None of them showed relapse of the disease for a follow-up period of 6 to 14 months after complete cessation of mycophenolate mofetil and prednisolone. No side effects were seen. CONCLUSION: Mycophenolate mofetil appears to be a safe and effective steroid-sparing agent in the treatment of CP.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Sequence, organization, chromosomal localization, and alternative splicing of the human serine protease inhibitor gene hurpin (PI13) which is upregulated in psoriasis.

Hurpin (protease inhibitor 13; PI13) is the most recently identified member of the ovalbumin family of serine protease inhibitors (serpins). It is expressed in human epidermal keratinocytes and is downregulated by exposure to ultraviolet irradiation. A role for hurpin in the proliferation or differentiation of keratinocytes has been proposed because of its strong expression in proliferating cells and its deregulated expression in the lesional epidermis of psoriatic patients. Here, we report the cloning, chromosomal localization, and complete sequence of the human hurpin gene. By PCR-based screening of the GeneBridge 4 radiation hybrid panel, we mapped the gene to chromosome 18q21.3, close to a known cluster of ov-serpin genes. Using the full-length cDNA for hurpin, we identified two clones from an arrayed genomic P1 placental library that contain the entire hurpin gene. Sequencing revealed that the gene covers 12.253 kb and is comprised of eight exons and seven introns. The exon--intron boundaries are identical in position and phasing to those in other members of the 18q serpin gene cluster, and analysis of hurpin variants indicated that modified functional inhibitors, differing only in the CD interhelical loop, can be generated by differential splicing of exon 3. These data show that hurpin is a typical member of the 18q ovalbumin-serpins most closely related to the serpins squamous-cell carcinoma antigens 1 and 2.

Alternative Splicing↗
PubMed2001

Aminolevulinic acid: pharmacological profile and clinical indication.

The role of aminolevulinic acid hydrochloride (ALA) in photodynamic therapy (PDT) of in situ neoplasias and tumours of epithelial tumours is steadily increasing and it has been shown to be the drug with most clinical use in PDT. In dermatology, topical PDT with ALA is already postulated to be the treatment of choice for actinic keratoses and superficial basal cell carcinomas. In gastroenterology, pulmonology, uro- and nephrology, neurology and gynaecology ALA has an important role as a photosensitiser not only in the diagnosis of neoplastic tissue but as therapy; first experiences have been made with PDT in these organs. Besides the therapeutic efficacy of this technique, the fluorescence of ALA-induced porphyrins can be effectively used to detect and delineate epithelial and endothelial neoplasms. In dermatology, other indications for ALA-treatment are non-tumoural applications, especially psoriasis, viral-induced diseases, or acne vulgaris. ALA is an effective compound in the diagnosis or therapy of various epithelial and endothelial neoplastic lesions.

Aminolevulinic Acid↗
PubMed2001

Topical tacrolimus for the treatment of inflammatory skin diseases.

Chronic inflammatory skin disorders, such as atopic eczema, can cause considerable impairment of life quality. Their treatment is mainly driven by systemic or topical glucocorticosteroids which have the risk of many side effects. Recently, immunosuppressive macrolides which act via the inhibition of cytokine expression in T-lymphocytes have been shown to exert good therapeutic potency in inflammatory skin disorders. Cyclosporin, widely used in transplantation medicine, is also effective in psoriasis and atopic eczema but is not suitable for topical treatment. Tacrolimus (FK506) has been found to be 10-100 times more potent than cyclosporin and to penetrate skin much better due to a lower molecular weight. Initial clinical investigations have shown efficacy of topical tacrolimus in patients with atopic eczema. Large multi-centre studies have proven that long-term therapy with 0.03% and 0.1% tacrolimus ointment reveals effectiveness and safety both in adults and in children with severe atopic eczema. A burning sensation at the site of application is the most frequently observed local side effect. Relevant systemic adverse events were not detected. In Japan and the US, the drug is already licensed for the treatment of atopic eczema. The European admission for the pharmaceutical market is expected in the year 2002. Tacrolimus represents a milestone in topical therapy of inflammatory skin disorders which has so far been dominated by corticosteroid formulations and gives hope for the development of further topical immunosuppressive agents of its class in the future.

Administration, Oral↗