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Biomedical subjects

E Schöpf

Publications and source records attributed to E Schöpf.

At least 19 recordsLinked to original sources
PubMed1992

High-dose UVA1 therapy in the treatment of patients with atopic dermatitis.

BACKGROUND: Besides glucocorticosteroids, there is currently no known effective therapy for patients with acute atopic dermatitis. OBJECTIVE: The therapeutic effectiveness of high-dose UVA1 irradiation in the management of patients with acute exacerbation of atopic dermatitis was examined. METHODS: Patients in the high-dose UVA1 group (n = 15) were irradiated with 130 joules/cm2 UVA1; the control group (n = 10) was treated with UVA-UVB therapy in a minimal erythema dose-dependent manner (total number of treatments 15). RESULTS: High-dose UVA1 irradiation was found to induce a significant clinical improvement of atopic dermatitis (p less than 0.001). In comparison with UVA-UVB therapy, significant differences in favor of high-dose UVA1 were observed (p less than 0.01). High-dose UVA1, but not UVA-UVB treatment, significantly reduced the elevated serum level of eosinophil cationic protein in patients with atopic dermatitis (p less than 0.003). CONCLUSION: These studies indicate that high-dose UVA1 irradiation may represent a novel phototherapeutic modality for the treatment of patients with an acute exacerbation of atopic dermatitis.

Adult↗
PubMed1992

Ultraviolet radiation effects on human keratinocyte ICAM-1 expression: UV-induced inhibition of cytokine-induced ICAM-1 mRNA expression is transient, differentially restored for IFN gamma versus TNF alpha, and followed by ICAM-1 induction via a TNF alpha-like pathway.

Human keratinocytes (KC) during the course of inflammatory dermatoses strongly express the surface molecule ICAM-1, which plays an important role in the generation of the epidermal inflammatory infiltrate by mediating leukocyte-keratinocyte interactions. Accordingly, KC ICAM-1 expression is known to be induced in vivo and in vitro by cytokines either via the TNF alpha/TNF beta or via the IFN gamma-mediated pathway. In contrast, ultraviolet (UV) radiation previously has been found to potently inhibit cytokine-induced KC ICAM-1 surface expression by a sublethal mechanism. In order to further define this novel immunosuppressive effect of UV light, the effects of in vitro UV radiation on ICAM-1 mRNA expression in transformed human KC (KB cells) were examined. Accordingly, UV light (0-100 J/m2) inhibited IFN gamma- as well as TNF alpha-induced ICAM-1 mRNA expression, if KC were cytokine stimulated immediately after irradiation. After a 12-h incubation period, however, IFN gamma responsiveness was found to be restored in irradiated cells, whereas restoration of responsiveness to TNF alpha required at least a 24-h recovery phase. Moreover, UV light alone did not alter ICAM-1 mRNA levels after 4, 12, or 24 h. After 48 h, however, a significant increase in ICAM-1 mRNA and surface expression in UV-irradiated KC could be observed. In addition, this increase could be superinduced by stimulation of irradiated KC with IFN gamma, but not with TNF alpha. UV-induced upregulation of ICAM-1 expression could be mimicked by stimulating unirradiated cells with supernatants derived from UV-irradiated cells. Addition of biologically active anti-TNF alpha antibodies to UV-irradiated cells or to supernatants derived from UV-irradiated KC, however, did not even partially abolish this ICAM-1-inducing activity. UV light thus seems to affect KC ICAM-1 mRNA expression in a biphasic manner: an early period of inhibition of cytokine-induced ICAM-1 expression is transient and followed by restoration of responsiveness to ICAM-1-inducing cytokines. Moreover, UV itself is able to induce ICAM-1 mRNA expression at this later time point via a TNF alpha-like pathway. These studies identify UV irradiation as a potent modulator of cytokine regulated ICAM-1 gene transcription with the capacity to induce both inhibitory as well as enhancing effects.

Blotting, Northern↗
PubMed1992

Effects of the immunosuppressive dipeptide L-leucyl-L-leucine O-methyl ester on epidermal Langerhans cells.

Pretreatment of newborn human foreskin epidermal cells (EC) with L-leucyl-L-leucine methyl ester (Leu-Leu-OME) was found to dramatically inhibit their ability to serve as alloantigen-presenting cells in a primary, one-way, allogeneic mixed epidermal cell-lymphocyte reaction (MECLR) without significantly affecting EC viability. The Leu-Leu-OME-induced MECLR inhibition could not be accounted for by a cytotoxic effect on epidermal Langerhans cells (LC), the class II major histocompatibility (MHC) antigen-bearing EC type that is fully responsible for alloantigen presentation in a primary allogeneic MECLR. Pretreatment with Leu-Leu-OME was found to inhibit the culture-induced increase in surface expression of HLA-DR molecules on LC. These findings suggest that in addition to its cytotoxic effect on cells containing high levels of dipeptidyl peptidase I, Leu-Leu-OME can also perturb alloantigen-presenting cells that are not killed by this agent by modulating HLA-D region antigen expression, perhaps through its capacity to neutralize acid compartments within cells. In addition, these studies support the notion that the culture-induced upregulation of class II MHC antigens on epidermal LC is functionally associated with the enhanced alloantigen-presenting capabilities that these cells display after short-term culture and suggest that newly synthesized class II antigens might be critical to the alloantigen-presenting cell capabilities of LC.

Adjuvants, Immunologic↗
PubMed1992

Serum eosinophil cationic protein (ECP) is a sensitive measure for disease activity in atopic dermatitis.

Atopic dermatitis (AD) is characterized by alterations in cellular and humoral immunity including elevated serum levels of IgE, IL-2 receptor (IL-2R) and eosinophil cationic protein (ECP). In order to evaluate the relevance of these serum parameters as indicators of disease activity, the concentrations of IgE, IL-2R and ECP were measured in serum samples of patients with an acute exacerbation of AD (n = 19) on admission to hospital and every 6 days up to discharge, and compared with those from normal non-atopic controls (n = 15). The severity of the disease in the AD patients was examined using an established clinical scoring system. On admission, AD patients showed significantly elevated serum levels of IgE, IL-2R and ECP compared with normal controls (P less than or equal to 0.0001). Clinical improvement was associated with a decrease of both the clinical score (P less than or equal to 0.001) and serum ECP levels (P less than or equal to 0.005). No significant changes in serum IgE and serum IL-2R were observed. In addition, there was a significant correlation between serum ECP and the clinical score (R = 0.67, P less than or equal to 0.001). These data indicate that serum ECP may be a helpful tool for monitoring disease activity in AD.

Acute Disease↗
PubMed1992

Human epidermal keratinocytes are a source of soluble ICAM-1 molecules.

A soluble form of the usually membrane-bound adhesion molecule ICAM-1 was detected in supernatants derived from human epidermal keratinocytes. Specifically, supernatants harvested from long-term cultured normal human keratinocytes, or from the spontaneously immortalized keratinocyte cell line HaCaT, did not contain significant amounts of sICAM-1, but shedding of sICAM-1 was found to be markedly induced upon stimulation of keratinocytes with rh IFN gamma. In contrast, cells from the two epidermoid carcinoma cell lines, KB and A431, constitutively shed significant amounts of sICAM-1 even without cytokine stimulation, and sICAM-1 contents in supernatants harvested from these cells were further increased upon stimulation of cells with rh IFN gamma. These studies indicate, that in addition to peripheral blood mononuclear cells and human melanoma cells, human epidermal keratinocytes constitute an important cellular source of sICAM-1. By binding to leukocyte LFA-1 molecules, keratinocyte-derived sICAM-1 may influence inflammatory responses in the skin. In addition, constitutive shedding of sICAM-1 by transformed human keratinocytes may represent a possible mechanism by which neoplastic keratinocytes escape from cytotoxicity.

Cell Adhesion↗
PubMed1992

High-dose-UVA1 phototherapy: a novel and highly effective approach for the treatment of acute exacerbation of atopic dermatitis.

High-Dose-UVA1 irradiation has recently been found to be a new, prompt-acting and highly effective phototherapeutic approach to the treatment of patients with acute exacerbation of atopic dermatitis. This therapeutic efficacy was demonstrated by a marked improvement of clinical symptoms as well as of laboratory parameters, which were found to reflect disease activity in atopic dermatitis. Investigation of the photoimmunological mechanisms responsible for the therapeutic effectiveness of this modality indicates that eosinophils and epidermal Langerhans cells may be targets for High-Dose-UVA1.

Acute Disease↗
PubMed1992

[Grzybowski type eruptive keratoacanthomas and ectropion. A therapeutic problem].

Eruptive Grzybowski-type keratoacanthoma is a rare variant of multiple keratoacanthoma and is not accompanied by internal malignancies. Up to now only 16 cases of eruptive Grzybowski-type keratoacanthoma have been described in the literature. Eruptive and solitary keratoacanthomas cannot be distinguished histologically. The multiplicity of skin lesions may be due to a genetic background. Our patient presented with multiple eruptive keratoacanthomas, ectropion and a mask-like face. Conservative treatment, e.g. with etretinate, did not lead to any improvement of symptoms in this case. Therefore surgical therapy was recommended for the patient's ectropion.

Adult↗
PubMed1991

A need to intensify drug surveillance in Germany.

Despite all its limitations, the spontaneous reporting system still forms the basis for drug safety assessments in the Federal Republic of Germany. Although there have been some promising attempts to standardise the methodology of detecting, analysing and evaluating adverse drug events (ADEs) in certain clinico-pharmacological institutes and psychiatric departments, the approaches have not been integrated and are used only locally. The only exception is the Freiburg Documentation Centre for Severe Skin Diseases, which is attempting comprehensive, country-wide documentation of toxic epidermal necrolysis (Lyell's syndrome) and Stevens-Johnson syndrome. We show that surveillance of 40% of all hospital beds would allow the acquisition of reliable data even on rare and serious AEs which could then be extrapolated in a statistically meaningful way. The medical societies in Germany have traditionally taken a leading role in establishing standards for the preclinical and clinical investigation of new drug compounds. We suggest that they also make it their task to define the framework for an intensified adverse events monitoring system, since it is the patient who ultimately benefits from a quantification of drug therapy risks.

Bed Occupancy↗
PubMed1991

Toxic epidermal necrolysis and Stevens-Johnson syndrome. An epidemiologic study from West Germany.

Little work has been carried out on the epidemiology of the two serious skin reactions--toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS). We collected details of all the hospitalized cases of TEN and SJS in the Federal Republic of Germany for the years 1981 through 1985 inclusive. Inquiries by telephone, letter, and personal visits produced an overall response of 91%; 259 cases of TEN and 315 cases of SJS were identified. From these data, we were able to calculate an overall annual risk of 0.93 and 1.1 per million for TEN and SJS, respectively. The average age group was higher for TEN (63 years) than for SJS (25 years). Women are markedly more at risk for TEN in the ratio of 2:1, these figures being reversed for SJS. The mortality was 34% (87/259) for TEN and only 1% (2/315) for SJS. An association with previous medication defined as "definite, probable, possible" could be established for 89% of cases of TEN and 54% of cases of SJS. The drugs most commonly involved were antibiotics (TEN, 40%; SJS, 34%), followed by the analgesics (TEN, 23%; SJS, 33%). As with the drug groups, the incidences being based on the defined daily doses, were high for sulfonamides, beta-lactam antibiotics, and some nonsteroidal anti-inflammatory drugs.

Adult↗
PubMed1991

Effect of tumour necrosis factor alpha in vivo on human granulocyte oxidative metabolism.

Tumour necrosis factor alpha (TNF alpha) effectively stimulates the oxidative metabolism of human PMN in vitro. Moreover, preincubation of PMN with TNF alpha has been shown to result in an altered response of the target cells to subsequent stimulation. In the present study the response of PMN to stimulation in vitro was investigated in patients with metastasizing malignant melanoma receiving bolus injections of recombinant human TNF alpha as therapy. TNF alpha was given daily for 5 days. Blood samples were taken prior to TNF alpha administration on days 1 to 4 and on day 8. Lucigenin-enhanced chemiluminescence (CL) was used as a sensitive measure of granulocyte oxidative metabolism. PMN were stimulated with TNF alpha, TNF beta, GM-CSF, PMA, opsonized zymosan and f-met-leu-phe. A significant increase in CL responses was detected upon stimulation with TNF alpha, TNF beta and PMA from day 1 to day 3, whereas no significant changes were observed for the background activity or when GM-CSF or opsonized zymosan were used as stimuli. On day 4 all CL responses returned to the day 1 starting level. A further significant decrease was observed on day 8 upon stimulation with TNF alpha, TNF beta and GM-CSF. In contrast, the effect induced by f-met-leu-phe reached a maximum on day 4, but the CL response was found to be at the starting level on day 8. The results indicate that TNF alpha induces significant changes in PMN response to distinct stimuli in vivo. Moreover, it may be possible that continuous daily infusions with TNF alpha induce a hyposensitization of PMN oxidative metabolism.

Acridines↗
PubMed1991

Eosinophil cationic protein in sera of patients with atopic dermatitis.

Patients with atopic dermatitis frequently show elevated blood eosinophil counts, and eosinophil-derived major basic protein has been demonstrated in the eczematous skin from patients with atopic dermatitis. To evaluate further the role of eosinophils in the pathogenesis of atopic dermatitis, the concentration of eosinophil cationic protein was measured in serum samples of 42 patients with moderate to severe disease. The results were compared with those obtained in 32 patients with psoriasis with (n = 9) or without (n = 23) a history of inhalant allergy, 12 patients with a history of pseudoallergic reactions to acetylsalicylic acid, 14 patients with a history of inhalant allergy, and 31 nonatopic healthy control subjects. Eosinophil cationic protein levels were significantly increased in the serum of patients with atopic dermatitis (p less than or equal to 0.005) and patients with a history of pseudoallergic reactions to acetylsalicylic acid (p less than or equal to 0.01). There was no significant difference between eosinophil cationic protein levels in patients with psoriasis or a history of inhalant allergy and in control subjects. Moreover, eosinophil cationic protein levels did not differ significantly in psoriasis patients with or without inhalant allergy. These studies support the concept of an active participation of eosinophils in atopic dermatitis and point to a possible role for eosinophils in pseudoallergy.

Adolescent↗
PubMed1991

Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis.

Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine that is produced by monocytes and keratinocytes upon stimulation. Because psoriasis is a skin disease characterized by a hyperproliferative activity of keratinocytes and an inflammatory infiltrate, in the present study IL-6 production of monocytes and keratinocytes of patients with psoriasis was investigated. Peripheral blood mononuclear cells (PBMC) derived from psoriatics, atopics, and healthy controls were incubated for 24 h and, subsequently, supernatant IL-6 activity was measured using an IL-6-dependent hybridoma cell line (B9). Compared to controls and atopics, PBMC of psoriatics produced significantly increased amounts of biologically active IL-6. These findings were also confirmed by Western blot analysis using a specific antiserum directed against IL-6. Moreover, when the sera of the same patients were tested for IL-6 activity, sera of psoriatics contained significantly elevated amounts of circulating IL-6 in comparison to samples from atopics and healthy controls. In contrast to normal or uninvolved skin, keratinocytes in psoriatic lesions were remarkably positive for IL-6 as detected by immunohistochemistry and in situ hybridization. In addition, IL-6 also was found to induce its own synthesis and release by monocytes. These findings indicate that keratinocytes and monocytes in psoriasis are activated to produce increased amounts of IL-6, which may be one of the mediators involved in the regulation of both local and systemic inflammatory reactions occurring in skin diseases such as psoriasis.

Adult↗
PubMed1991

55-kd tumor necrosis factor receptor is expressed by human keratinocytes and plays a pivotal role in regulation of human keratinocyte ICAM-1 expression.

Tumor necrosis factor alpha (TNF alpha) is a potent modulator of human keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression. TNF alpha is known to exert its biologic effects by binding to specific cell-surface receptors. Two distinct TNF binding molecules, the 55-kd and the 75-kd TNF receptor (TNFR) recently have been found to be expressed by human cells. These two receptor types are independently regulated and differ markedly in their intracellular regions, indicating functional dichotomy. In order to gain further insight into the mechanisms underlying ICAM-1 regulation in human keratinocytes, in the present study, the receptor molecules mediating TNF alpha induced ICAM-1 upregulation in human keratinocytes was defined. Human keratinocyte TNFR expression was assessed using monoclonal antibodies that specifically recognize the 55-kd or the 75-kd TNFR. Using FACS analysis, normal (HNK) as well as transformed (KB) human keratinocytes were found to react with anti-55-kd TNFR, but not anti-75-kd TNFR antibodies. These immunofluorescence data were confirmed by Northern blot analysis revealing clearly detectable amounts of mRNA specific for the 55-kd TNFR in KB cells. Incubation of human keratinocytes with anti-55-kd TNFR antibodies at 37 degrees C for 24 h increased ICAM-1 expression in a TNF alpha-like fashion. Moreover, the well known synergistic effect of IFN gamma plus TNF alpha on keratinocyte ICAM-1 induction could be mimicked by stimulation of cells with IFN gamma plus anti-55-kd TNFR antibodies. Synergistic ICAM-1 induction was not associated with increased expression of the 55-kd TNFR in IFN gamma-stimulated human keratinocytes. These studies indicate that human keratinocytes express the 55-kd TNF receptor and that this surface molecule may play an important role in regulation of human keratinocyte ICAM-1 expression.

Binding Sites, Antibody↗
PubMed1991

Toxic epidermal necrolysis in patients receiving glucocorticosteroids.

Despite the lack of evidence of an immunologically mediated mechanism for Toxic Epidermal Necrolysis (TEN), glucocorticosteroids are frequently used for the treatment of patients afflicted with TEN. We investigated the data of 216 patients with TEN for therapy with glucocorticosteroids prior to the beginning of TEN. The data had been collected between 1984 and 1985 during the epidemiological study on severe skin reactions in West-Germany spanning the years 1981-85. 11/216 (5%) patients could be traced, who had been treated with glucocorticosteroids for at least a week prior to the first dermatological sign of TEN. Glucocorticosteroids had been administered predominantly for neurological or neurosurgical conditions. The period of treatment ranged from 1 week to several months. Doses ranging between 7.5 and 325 mg prednisolone/per day were found. There were no major differences between patients with or without steroid therapy with regard to sex, age and lethality. The observation of TEN in patients receiving therapy with glucocorticosteroids raises questions about the usefulness of treating patients with TEN with glucocorticosteroids.

Adult↗
PubMed1991

Immunohistochemical investigation of dermal capillaries in chronic venous insufficiency.

Skin biopsies from the area of the medial malleolus of 24 patients with chronic venous insufficiency, of 5 patients without signs or history of chronic venous insufficiency and of seven corpses without manifestation of chronic venous insufficiency, were sectioned and stained with hematoxylin and eosin and with Ki-67, a monoclonal antibody expressed in the nuclei of proliferating cells. Hematoxylin- and eosin-stained sections of all specimens were assessed blindly to determine the state of capillary increase in stasis dermatosis. Twenty-four patients were found to have different stages of stasis dermatosis. During the examination of the Ki-67 frozen sections, close attention was paid to the capillary bed of all sections for any Ki-67-positive nuclei in capillary cells. None of the three groups showed positive staining of nuclei in capillary cells. This finding proves that there is no capillary proliferation, but an elongation and distension of the capillaries.

Adult↗
PubMed1991

Factor XIII-deficiency in the blood of venous leg ulcer patients.

Pericapillary fibrin cuffs are probably involved in the pathogenesis of venous leg ulcers. Factor XIII (Fibrin stabilizing factor) is of importance in wound healing. Its activity, which may affect ulceration, was found to be significantly reduced in the blood of venous leg ulcer patients and in post-phlebitic patients, compared with healthy controls.

Chronic Disease↗
PubMed1991

Production of interleukin-2 by mononuclear cells in vitro in patients with atopic dermatitis and psoriasis. Comparison with serum interleukin-2 receptor levels.

Atopic dermatitis is associated with profound immunological alterations, in particular decreased lymphoproliferative responses upon stimulation with T-cell mitogens. T-cell blastogenesis involves the production of the soluble cytokine interleukin-2 (IL-2), which in turn upregulates the expression of its own receptor. To investigate the potential role of this cytokine for the pathomechanisms present in atopic dermatitis, 24-h supernatants of PHA-stimulated peripheral blood mononuclear cells from patients with atopic dermatitis (n = 30) of a moderate to severe disease activity were tested for IL-2 activity. In addition, serum concentrations of soluble interleukin-2 receptor (IL-2R) were measured. Non-atopic healthy controls (n = 19) and patients with psoriasis (n = 20), an inflammatory skin disorder with distinct pathogenesis, served as controls. In comparison with psoriasis patients and normal controls, PHA-stimulated mononuclear cells of atopic dermatitis patients released significantly less IL-2 into supernatants. Moreover, there was an inverse correlation between IL-2 concentrations and body surface involvement or serum IgE levels. In contrast, serum IL-2R levels were significantly elevated in both atopic dermatitis and psoriasis, as compared with healthy controls. Furthermore, IL-2R levels in atopic dermatitis patients showed a significant correlation with IgE levels and body surface involvement. The data indicate that T cell activation may occur in both skin diseases. Atopic dermatitis, however, is further characterized by the decreased capacity of mononuclear cells to release IL-2 upon stimulation in vitro.

Adolescent↗