[Silica-induced scleroderma in miners in former uranium ore mining (Wismut AG)]. / Quarzinduzierte Sklerodermie bei Bergleuten im früheren Uranerzbergbau (Wismut AG).

As part of the reappraisal of the legacy of Wismut AG, 12 patients with silica-induced scleroderma among underground uranium ore mine workers (Wismut AG) under long-term exposure to silica fine dust, as well as radon and its daughter products, during the 1960s and 1970s are reported on. Silica-induced scleroderma is clinically, serologically and immunologically indistinguishable from idiopathic systemic sclerosis. In experimental studies, endothelial cells, monocytes and fibroblasts, as well as their synthesis rates and the release of cytokines and chemokines, were activated by silica fine dust in a way that is consistent with the pathophysiological processes in idiopathic systemic sclerosis. It was not possible to achieve recognition of silica-induced systemic sclerosis as an occupational disease in Germany.

Prostacyclin analogue iloprost influences endothelial cell-associated soluble adhesion molecules and growth factors in patients with systemic sclerosis: a time course study of serum concentrations.

Systemic sclerosis is a connective tissue disorder with unclear aetiology and pathogenesis. However, there is evidence that microvascular changes belong to the early symptoms of the disease. These are associated with increased serum levels of markers of endothelium activation, such as adhesion molecules and growth factors. The stable prostacyclin analogue iloprost is licensed for vascular symptoms (Raynaud's phenomenon) and was recently shown to exert short-term effects on these markers. In this study, serum samples (n = 13) from patients with systemic sclerosis were examined for serum levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1, E-selectin, endothelin-1 and vascular endothelial growth factor over 6 months after iloprost infusions in order to detect possible long-term effects. Iloprost significantly reduced initially elevated levels of these markers, partly until the end of the observation period (E-selectin, VCAM-1, endothelin-1). These effects provide serological evidence for the benefits of iloprost infusions that are seen clinically in patients with systemic sclerosis.

[Causative agents of onychomycosis--a retrospective study]. / Onychomykosen--eine retrospektive Untersuchung zum Erregerspektrum.

BACKGROUND: Dermatophytes, yeasts and moulds all are potential causative agents of onychomycosis. The aim of this study was to determine the percentage of cases of onychomycoses caused by each group. In addition, the responsible genus and species was identified for each nail infection. PATIENTS AND METHODS: In a retrospective study performed at the Department of Dermatology of the Leipzig University, 5,077 nail samples from 4,177 patients--2,240 women and 1,937 men--with a variety of nail changes--not just onychomycosis--were investigated. 75% were toenails, 23% fingernails, and 2% from both sites. RESULTS: Both microscopic and/or cultural detection of fungi (dermatophytes, yeasts and moulds) were successful in 54% of samples. Causative fungal agents were: 68% dermatophytes, 29% yeast, and 3% moulds. The most frequently detected dermatophyte species were T. rubrum (91%), and T. mentagrophytes (7.7%). Among yeasts, C. parapsilosis (42%) was most common,followed by C. guilliermondii (20.1%), C. albicans (14.2%), and Trichosporon spp. (10%). Scopulariopsis brevicaularis (43%) was the most frequent mould. The percentage of mixed fungal infections was 22%. CONCLUSIONS: Dermatophytes, in particular T.rubrum, but also T. mentagrophytes, are the most frequently isolated causative agents in onychomycosis. In addition, yeasts may be isolated relatively frequently, while moulds are uncommon.

[MCTD--mixed connective tissue disease]. / MCTD--Mixed Connective Tissue Disease.

Mixed connective tissue disease is a disease entity characterized by overlapping symptoms of lupus erythematosus (LE), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA). Diagnostic criteria include high titers of antibodies against U1RNP as well as the presence of at least 3 of 5 of the following clinical features: edema of hands, synovitis, myositis, Raynaud phenomenon and acroscierosis. In terms of the pathogenesis, genetic as well as infectious (viral) factors appear to play a role. The acceptance of MCTD as a distinct disease entity is controversial. Terms such as "undifferentiated connective tissue disease" or "overlapping syndromes" are not helpful. One-quarter of MCTD patients transform into LE, while one-third progress to SSc. Therapeutic recommendations are glucocorticoids in combination with immunosuppressive agents and endothelin receptor antagonists. Double blind studies are not available. The prognosis is relatively good. Causes of death include pulmonary hypertension, infections and both pulmonary and cardiac failure.

Aggressive undifferentiated squamous cell carcinoma in an immunosuppressed patient after kidney transplantation.

A 56-year-old man developed a highly aggressive squamous cell carcinoma (SCC) on the upper back five years ago renal transplantation and subsequent immunosuppression. The tumor was excised using the three-dimensional micrographic technique; after the formation of granulation tissue, the wound was covered with a Meshgraft. His cyclosporine A dose was reduced from 2.5 to 2.0 mg/kg. The patient was counseled on sun avoidance and use of sunscreens, as well as placed on low-dose oral acitretin and imiquimod 5% cream to control actinic keratoses. He is followed every 3 months by a dermatologist and has shown no evidence of recurrence over 2 years.

Intravenous dexamethasone-cyclophosphamide pulse therapy in comparison with oral methylprednisolone-azathioprine therapy in patients with pemphigus: results of a multicenter prospectively randomized study.

BACKGROUND: Pemphigus is a potentially life-threatening autoimmune blistering skin disease usually treated with high-dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone-cyclophosphamide (D/C) pulse therapy with a methylprednisolone-azathioprine (M/A) therapy in 22 patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. PATIENTS AND METHODS: The 11 patients of the M/A group were treated with daily doses of methylprednisolone (initially 2 mg/kg body weight) and azathioprine (2-2,5 mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11 patients consisted of intravenous administration of 100 mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500 mg) on day one. Pulses were initially repeated every 2-4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50 mg) was given daily for 6 months. RESULTS: Within 24 months after treatment initiation, 5/11 patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3 patients) and 6/11 patients had a progression. In the M/A group, there were remissions in 9/11 patients (complete remissions after discontinuation of therapy in 3 patients) and progression in 1/11 patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). CONCLUSION: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy.

Scleroderma and pseudo-scleroderma: uncommon presentations.

Scleroderma is characterized by major clinical symptoms, but a number of unrelated disease may mimic these features more or less completely. Even scleroderma itself sometimes presents in an unusual manner. This article deals with uncommon presentations of true scleroderma and its variants and pseudo -scleroderma diseases.

MEL4B3, a novel mRNA is induced in skin tumors and regulated by TGF-beta and pro-inflammatory cytokines.

Tumor-stroma interactions play a decisive role in the growth and metastasis of solid tumors, and involve signalling either by soluble mediators or direct cell-cell interaction. Here, we report the isolation and characterisation of a novel cDNA (MEL4B3), which is induced in cultured dermal fibroblasts exposed to supernatants of melanoma cell lines. MEL4B3 shares high homology with two predicted cDNA sequences for which no activity has so far been described. In situ hybridisation revealed the expression of MEL4B3 in malignant melanoma increasing with tumor depth; in basal cell carcinoma and in squamous cell carcinoma. MEL4B3 was barely detectable in normal skin or non-malignant melanocytic naevi. Furthermore, MEL4B3 was expressed at high level in the epidermis of psoriatic skin. In vitro, the expression of MEL4B3 was found to be induced by the exposure of human dermal fibroblasts to melanoma cell culture supernatants or to transforming growth factor-beta, interleukin-1 and tumor necrosis factor-alpha. The expression MEL4B3 therefore reflects closely cell activation occurring during tumor growth, metastasis and inflammation.

Interaction of human Thy-1 (CD 90) with the integrin alphavbeta3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium.

The expression of the alphavbeta3 integrin (CD51/CD61) on human melanoma cells has been shown to be associated most closely with tumor progression and metastases formation in melanoma. Here, we demonstrated a specific interaction of the alphavbeta3 integrin on melanoma cells with the human Thy-1, an inducible cell adhesion molecule expressed on the cell surface of activated endothelial cells (EC). The interaction was shown by the binding of purified Thy-1 protein to alpha(V)beta(3) transfected cells, to alphavbeta3-expressing melanoma cells and to purified alpha(V)beta(3) integrin. Moreover, melanoma cells adhere specifically to Thy-1 transfectants via alphavbeta3 on melanoma cells showing the functional relevance of this interaction for cell adhesion. Finally, the importance of the alphavbeta3/Thy-1 interaction for the adhesion of melanoma cells to the activated endothelium was confirmed under static and flow conditions by the inhibition of melanoma cell adhesion to and transmigration across activated EC by blocking the alphavbeta3/Thy-1 interaction. In conclusion, we have identified a new pair of adhesion molecules Thy-1 and alphavbeta3 mediating the interaction of melanoma cells and activated EC. These data explain at least in part the high tumorigenicity of alphavbeta3-expressing melanoma cells and the association of alphavbeta3-positive melanoma cells with a high risk of metastasis and poor prognosis.

Human Thy-1 (CD90) on activated endothelial cells is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18).

Leukocyte recruitment in response to inflammatory signals is in part governed by interactions between endothelial cell receptors belonging to the Ig superfamily and leukocyte integrins. In our previous work, the human Ig superfamily glycoprotein Thy-1 (CD90) was identified as an activation-associated cell adhesion molecule on human dermal microvascular endothelial cells. Furthermore, the interaction of Thy-1 with a corresponding ligand on monocytes and polymorphonuclear cells was shown to be involved in the adhesion of these leukocytes to activated Thy-1-expressing endothelial cells. In this study, we have identified the specific interaction between human Thy-1 and the leukocyte integrin Mac-1 (CD11b/CD18; alphaMbeta2) both in cellular systems and in purified form. Monocytes and polymorphonuclear cells were shown to adhere to transfectants expressing human Thy-1 as well as to primary Thy-1-expressing human dermal microvascular endothelial cells. Furthermore, leukocyte adhesion to activated endothelium as well as the subsequent transendothelial migration was mediated by the interaction between Thy-1 and Mac-1. This additional pathway in leukocyte-endothelium interaction may play an important role in the regulation of leukocyte recruitment to sites of inflammation.

Bullous pyoderma gangrenosum complicated by disseminated intravascular coagulation with subsequent myelodysplastic syndrome (chronic myelomonocytic leukemia).

A 33-year-old woman developed a bullous PG precursing a chronic myelomonocytic leukemia (CMML) complicated by life-threatening, disseminated, intravascular coagulation after administration of systemic corticosteroids in combination with immunosuppressant and antibiotic agents. Although the association between PG and leukemia, as well as the coincidence of disseminated intravascular coagulation (DIC) and leukemia, is well known, a premonitoring effect of PG in combination with DIC preceding the diagnosis of chronic myelomonocytic leukemia in the same patient has not been reported recently.

Severe oral allergy syndrome and anaphylactic reactions caused by a Bet v 1- related PR-10 protein in soybean, SAM22.

BACKGROUND: Anaphylactic reactions to soy products have been attributed to stable class 1 food allergens. OBJECTIVE: IgE- mediated reactions to a soy-containing dietary food product in patients allergic to birch pollen were investigated. METHODS: Detailed case histories were taken from 20 patients. Their sera were analyzed for IgE (UniCAP) specific for birch, grass, mugwort, the recombinant birch allergens rBet v 1 and rBet v2, and soy protein. Extracts from birch pollen, soy isolate, rBet v 1, and the recombinant PR-10 soy protein rSAM22 were coupled to paper disks or nitrocellulose for IgE measurements (enzyme allergosorbent test) or Western blot analysis. Enzyme allergosorbent testing, Western blot inhibition, and histamine release studies were performed with the same allergens. RESULTS: Most patients (17/20) experienced facial, oropharyngeal, and/or systemic allergic symptoms within 20 minutes after ingesting the soy product for the first time. Birch pollen allergy (16/20) was common, along with oral allergy syndrome to apple (12/20) or hazelnut (11/20). IgE levels to birch and Bet v 1 but not to other inhalants were high in 18 of 20 patients. Significant IgE binding to rSAM22 occurred in 17 of 20 patients. Blot experiments with the soy isolate revealed IgE-binding bands at 17 kd (15/20), 22 kd (1/20), and 35 to 38 kd (2/20); the former was inhibited by preincubation of the sera with rBet v 1 or rSAM22. Birch extract and soy isolate, rBet v 1, and rSAM22 induced dose-dependent histamine release in the nanomolar range. CONCLUSION: Immediate-type allergic symptoms in patients with birch pollen allergy after ingestion of soy protein-containing food items can result from cross-reactivity of Bet v 1 -specific IgE to homologous pathogenesis-related proteins, particularly the PR-10 protein SAM22.

In vitro activity of phytosphingosines against Malassezia furfur and Candida albicans.

Long-chain sphingoid bases, e.g. phytosphingosine, sphingosine and sphinganine, main constituents of the stratum corneum, can strongly inhibit the growth of microorganisms that are known to have undesirable effects on the skin. The aim of this study was to investigate the in vitro activity of different phytosphingosine preparations against Malassezia furfur, and, in comparison, against the common facultative pathogenic yeast Candida albicans. An agar dilution test for minimum inhibitory concentration (MIC) investigation of phytosphingosine base, phytosphingosine lactic acid salt, phytosphingosine HCl, and phytosphingosine glycolic acid salt was carried out using D.S.T. agar containing 2% olive oil and 0.2% Tween 80, to allow growth of the lipophilic yeast. M. furfur growth inhibition in vitro could be achieved only at extremely high phytosphingosine concentrations. Phytospingosine base had the lowest MIC value (mean 6,250 microg/ml, corresponding to 0.63% of phytospingosine in the agar). For the different phytosphingosine salts--lactic acid salt, HCl and glycolic acid salt--4-8 fold higher MIC values were noted. Unexpectedly, there was a growth stimulating effect of Malassezia at lower phytosphingosine concentrations. In comparison, growth of Candida albicans strains was inhibited at phytosphingosine concentrations between 152 and 269 microg/ml.

Lysine acetylsalicylate decreases proliferation and extracellular matrix gene expression rate in keloid fibroblasts in vitro.

BACKGROUND: In genetically predisposed individuals keloids are formed as benign collagenous tumors. OBJECTIVE: The purpose of this study was to investigate whether the proliferation and matrix gene expression of keloid fibroblasts is differently influenced by the anti-inflammatory active drug lysine acetylsalicylate (LAS) when compared to normal skin fibroblasts in vitro. METHODS: Normal skin and keloid fibroblasts derived from human donors were compared. RESULTS: Excessive scarring and the formation of keloids are (at least in part) due to an overproduction of collagen types I and III. The results show a significant dose-dependent anti-proliferative effect of lysine acetylsalicylate. At the level of gene expression we observed a pronounced inhibitory effect of LAS on procollagen I and III mRNA synthesis, whereas matrix metalloproteinase 1 and tissue inhibitor of metalloproteinases 1 were not altered. CONCLUSIONS: Further clinical studies are planned to evaluate these effects of a high-dose treatment of keloids with LAS.