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H M Ockenfels

Publications and source records attributed to H M Ockenfels.

17 recordsLinked to original sources
PubMed2003

[Trigger factors for psoriasis].

Psoriasis is often defined as a disease in which there is a genetic predisposition but environmental stimuli ("trigger factors") are also necessary for clinical expression. Various endogenous and exogenous factors can either induce or exacerbate the clinical features. Knowledge of these factors is of primary importance in clinical practice. This review focuses on the most common environmental trigger factors (infection/superantigens, injury/Köbner phenomenon, stress/neuropeptides, smoking and alcohol) and evaluates the clinical and experimental concepts to explain "environmentally" triggered psoriasis.

Autoantibodies↗
PubMed2003

Ultraviolet B 308-nm excimer laser treatment of psoriasis: a new phototherapeutic approach.

BACKGROUND: Excimer laser-derived 308-nm ultraviolet (UV) B therapy is a new alternative for treating psoriasis by phototherapy. Some studies have been made showing the effectiveness of intralesional phototherapy technology in treating psoriasis. However, there has been no information available so far with regard to the cumulative dosage on a larger group of patients and on therapy optimized treatment strategies. OBJECTIVES: One hundred and twenty psoriatic patients were treated according to standard protocol to define the effectiveness. Our aim was to develop new parameters and determine whether effectiveness could be improved and whether treatment exposure, the cumulative UVB dose and adverse effects could be minimized. METHODS: Initially, the excimer laser's effectiveness in treating psoriasis was evaluated in an open prospective study according to standard protocol. This included 120 adult patients (67 female/53 male) with chronic plaque psoriasis and < 20% involved body surface. The initial dose was based on three multiples of a predetermined minimal erythema dose (MED). Patients were treated twice a week for the first 3 weeks, then once a week until clearance was achieved. The main parameters were the initial starting dose, psoriasis area and severity index (PASI), the number of treatments needed, the time in treatment and the cumulative dose needed to clear psoriatic plaques. Thereafter, 43 patients were treated as a second comparable group. Therapy began with a starter dose, defined as MED-I. MED-I was defined as a UVB 308-nm dose which provoked a visible increase in erythema after 24 h. In addition, the epidermal thickness of the plaques was measured on an individual basis by 20-MHz ultrasound and correlated to the MED-I. RESULTS: Of the patients who met the standard protocol, 65.7% were at least 90% clear after a maximum of 10 treatments; an even greater number (85.3%) showed a > or = 90% improvement in PASI after 13 sessions, while 14.7% of patients had only a < or = 50% PASI improvement. The cumulative UVB dose was 11.25 +/- 4.21 J cm-2 and the average treatment time was 7.2 weeks. Patients treated individually with the MED-I starter dose showed nearly identical rates of clearance (83.7%), but were clear in 7.07 +/- 2.15 sessions with a cumulative dose of 6.25 +/- 4.02 J cm-2. CONCLUSIONS: The majority of our patients benefited greatly from laser-derived 308-nm UVB therapy, which cleared skin lesions faster than conventional phototherapy. As this therapy targets only the involved skin, the thickness of the plaques and individual MED-I should determine the initial dose, thus increasing the effectiveness of the therapy. We propose that light therapy sparing uninvolved skin will become predominant in the future.

Adult↗
PubMed1998

[Contact eczema in housewives. Update from 1986 with reference to results of epicutaneous tests in 2,633 patients].

The development of hand eczema is a relatively commonly seem dermatosis in housewives. In 1986 we presented a first survey of potential contact dermatitis sources for a housewife. Now, we present an update in which we analyse the different contact sources in the household and grade them in comparison to the data of 1986. The results are based on the analysis of a large population of 2633 patients with the occupation "housewife" and the diagnosis "eczema" who have been seen in departments of dermatology belonging to the Information Network of Departments of Dermatology (IVDK).

Adult↗
PubMed1998

The antipsoriatic agent dimethylfumarate immunomodulates T-cell cytokine secretion and inhibits cytokines of the psoriatic cytokine network.

Interactions between infiltrating T cells and keratinocytes via the secretion of the TH1 cytokines interleukin (IL) 2 and interferon gamma (INF-gamma), the keratinocyte growth factor transforming growth factor alpha (TGF-alpha) and the cytokines IL-6 and IL-8 are thought to be the predominant mechanisms inducing skin lesions in psoriatic patients. Systemic treatment of psoriasis with fumaric acid derivatives (FAEs) has been reported to be effective in the treatment of psoriasis, but the mode of action is still unknown. To clarify this phenomenon, keratinocytes from psoriatic patients as well as from healthy volunteers were mono- and cocultured with HUT 78 T cells with/without the addition of FAEs; the cytokine concentrations were then measured in the culture supernatants. Furthermore, mRNA expression was determined in epidermal growth factor (EGF) -activated keratinocytes as well as in phytohaemagglutinin (PHA)-activated HUT 78 T cells. Only dimethylfumarate (DMF) diminished IL-6 and TGF-alpha secretion in the psoriatic cocultures. However, it did not have this effect on cocultures from control subjects or on monocultures. DMF suppresses EGF-induced TGF-alpha mRNA induction in psoriatic keratinocytes. DMF inhibited INF-gamma secretion in all cultures but stimulated the IL-10 secretion. This immunomodulation away from the TH1 cytokine IFN-gamma to the TH2 cytokine IL-10 was confirmed in HUT 78 T cells by Northern blot analysis. An increased number of eosinophils is a known side-effect in patients treated with this drug, suggesting a clinical relevance of this immunomodulation in vivo. This immunomodulation and the suppression of cytokines from the psoriatic cytokine network could be responsible for the beneficial effect of DMF in the treatment of a hyperproliferative and TH1 cytokine-mediated skin disease.

Adult↗
PubMed1997

Contact allergy in patients with periorbital eczema: an analysis of allergens. Data recorded by the Information Network of the Departments of Dermatology.

BACKGROUND: Periorbital eczema may be an expression of a constitutional disease or an irritant or allergic dermatitis. An allergic contract dermatitis is believed to be the most common cause. OBJECTIVE: We tried to determine which allergens may cause an allergic contact dermatitis and if there exists a leading allergen. METHODS: 609 patients with periorbital eczema were assessed with patch testing in 22 hospitals to evaluate the relevance of an allergic contact dermatitis in the pathogenesis of periorbital eczema. Additionally, 116 patients were tested with their own products. RESULTS: 81% of the cases involving the eyelids were women. A relevant allergic contact dermatitis was found in 52% of the patients with periorbital eczema. Furthermore, a positive patch test was present in every third patient with the clinical diagnosis of an atopic dermatitis. Antibiotics, phenylephrine and thimerosal could be determined to be the leading allergens responsible for allergic periorbital eczema. Positive reactions for potassium dichromate and fragrance mix occurred less frequently in patients with periorbital eczema. 132 positive reactions were found in patients tested with their own products, including 33% with a positive reaction to eye ointments, 15% to face creams, 10% to eye shadows, 10% to makeup, 10% to shampoos and 4% to nail varnish. Only 6% reacted to perfume. CONCLUSION: The data underline the importance of performing patch tests in the case of periorbital eczema, especially in atopic patients.

Adult↗
PubMed1996

Inhibition of T cell cAMP formation by cyclosporin A and FK506.

The influence of the immunosuppressants, cyclosporin A (CsA) and FK506, on cAMP formation was studied in T cells from healthy controls and patients with psoriasis. While basal cAMP levels were not affected, CsA (1 microM) and FK506 (2 nM) prevented the isoprenaline (0.1 microM)-induced increase in cAMP formation. Half-maximal inhibition by FK506 and CsA was observed at about 0.2 nM and 20 nM, respectively. In addition, both agents significantly reduced (by about 50%) the forskolin (8 microM)-stimulated cAMP formation. No differences were noted in cAMP responses (basal, stimulation by isoprenaline, inhibition by CsA and FK506) of T cells from healthy controls and psoriatic patients. We conclude that CsA and FK506 potently and efficiently interfere with the stimulatory adenylyl cyclase pathway in T cells and that regulation of T cell cAMP formation is apparently not altered in psoriasis.

Adult↗
PubMed1996

Lithium and psoriasis: cytokine modulation of cultured lymphocytes and psoriatic keratinocytes by lithium.

The predominant cutaneous side effect of lithium is the exacerbation or aggravation of psoriasis, but the pathogenesis is still unclear. The hyperproliferation of keratinocytes and a dense lesional infiltrate of mononuclear cells are the hallmarks of psoriatic skin lesions. Interactions between keratinocytes and T cells are thought to be one reason for an increased secretion of proinflammatory cytokines and growth factors. To investigate whether lithium influences cytokines of the "psoriatic cytokine network', we established a coculture model with keratinocytes from psoriatic patients and from healthy controls cultured with HUT 78 lymphocytes and measured the cytokine levels of Il-2, Il-6, Il-8, IFN gamma and TGF alpha in the culture supernatants after treatment with lithium. Il-6 levels were slightly elevated in the supernatants obtained from psoriatic and control keratinocyte cultures after lithium treatment, but IFN gamma and Il-2 levels were elevated only in the lithium-treated cocultures with psoriatic keratinocytes. In contrast, these two cytokines were not affected by lithium in HUT 78 monocultures or in cocultures with normal epidermal cells. We also found slightly elevated TGF alpha levels in lithium-treated psoriatic cocultures but not in control cultures. We therefore demonstrated that lithium influences the cell communication of psoriatic keratinocytes with HUT 78 lymphocytes by triggering the secretion of TGF alpha, Il-2 and, massively, IFN gamma. It seems possible that lithium also influences similar parts of the psoriatic cytokine network in vivo.

Adult↗
PubMed1996

Differential expression of tissue inhibitor of metalloproteinases-2 by cutaneous squamous and basal cell carcinomas.

Tumor cell invasion and metastasis are considered to represent a multistep process leading to the degradation of the extracellular matrix by proteolytic enzymes. The functional activity of matrix metalloproteinases (MMPs) is controlled by tissue inhibitor of metalloproteinases-2 (TIMP-2), which has been shown to inhibit tumor cell invasion and metastasis in vitro and in vivo. To assess the role of TIMP-2 in skin-derived epithelial tumors, we have analyzed the expression of TIMP-2 mRNA in primary tissue samples from human cutaneous basal (BCC) and squamous cell carcinoma (SCC) for a correlation with their different invasive and metastatic potential. Comparative quantitative analysis of TIMP-2 mRNA levels by Northern blot hybridization demonstrated significantly higher TIMP-2 tissue levels in BCC than in SCC, indicating an inverse correlation between TIMP-2 expression and the metastatic capacity of these tumors in vivo. By in situ hybridization, tumor stromal cells were identified as the principal source of TIMP-2 mRNA in both BCC and SCC. A comparable distribution has been reported previously for several matrix metalloproteinases in cutaneous BCC and SCC, indicating co-localization of metalloproteinases with their respective inhibitor. These results may suggest that TIMP-2 substantially contributes to the biological behavior of epithelium-derived skin tumors by significantly inhibiting tumor cell metastasis.

Basal Cell Carcinoma↗
PubMed1996

The effect of cyclosporin A and FK 506 on the cAMP content in psoriatic keratinocytes.

FK 506 and cyclosporin A (CyA) are two immunosuppressive drugs which are known to be effective in the treatment of psoriasis by inhibiting the activation of T cells. In contrast, their influence on the proliferation of keratinocytes is discussed controversially. The second messenger cyclic adenosine monophosphate (cAMP) has been regarded as a regulator for cell growth and proliferation for 20 years. Hyperproliferation of many cells and particularly of psoriatic keratinocytes was speculated to be due to a decrease in cAMP levels in the psoriatic epidermis, whereas new findings could not confirm these observations. To clarify this discussion we determined the intracellular cAMP content in isoprenaline-stimulated keratinocytes from psoriatics and controls after treatment with CyA or FK 506. Ethanol and the beta-blocking drug propranolol served as controls. The basal level of cAMP and the response to isoprenaline in psoriatic keratinocytes did not differ from those of controls. CyA dramatically reduced the cAMP level and FK 506 just slightly diminished it in a dose-dependent manner. Both drugs diminished the cAMP level more effectively in the keratinocytes from lesional psoriatic skin than in keratinocytes from controls. These data provide evidence that CyA influences early signal transduction pathways by depressing the intracellular cAMP in keratinocytes. This supports the view of other groups that CyA and perhaps also FK 506 influence not only immuno-competent cells but also keratinocytes in the treatment of psoriasis. Furthermore, it is doubtful that a low cAMP level is a positive regulator for cell growth and the hyperproliferation of psoriatic keratinocytes.

Adult↗
PubMed1996

Surgical excision of pseudotumorous pretibial myxedema.

Pretibial myxedema is a well-known clinical feature of autoimmune thyroid malfunction and is classically associated with Graves' disease. Its clinical course is frequently not related to the clinical control of the underlying thyroid disease. Treatment is primarily medical, consisting of oral and topical corticosteroids. We present a case of successful local excision of a pseudotumorous manifestation at the dorsum of the foot recalcitrant to multimodal medical and dermatological therapy.

Female↗
PubMed1996

Ethanol enhances the mitogen-driven lymphocyte proliferation in patients with psoriasis.

Ethanol has been reported to exacerbate psoriasis. Since immunological mechanisms are considered to be important for the pathogenesis of psoriasis, we compared the effects of ethanol on lymphocyte proliferation in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin in (PHA)-induced uptake of 3H-TdR to measure lymphocyte proliferation. Ethanol was added to cultures at concentrations ranging from 0.5 to 0.0005% (vol./vol.). We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (P < 0.002). Spontaneous blastogenesis in both controls and patients remained stable under ethanol. In controls, ethanol suppressed the PHA-driven lymphocyte proliferation in a dose-dependent fashion. By contrast, in patients with psoriasis ethanol significantly increased lymphocyte proliferation by 2-3 times (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally enhanced by minimal doses of ethanol.

Adult↗
PubMed1996

Ethanol enhances the IFN-gamma, TGF-alpha and IL-6 secretion in psoriatic co-cultures.

Evidence suggests an association between alcohol consumption and psoriasis. This relationship is still undefined, although long-term alcohol intake influences the immune system. Interactions between T cells and keratinocytes are important for the pathogenesis of psoriasis, by secretion of pro-inflammatory cytokines and growth factors in psoriatic skin. IL-2, IL-6, IL-8, IFN-gamma and TGF-alpha are hallmark cytokines in a psoriatic cytokine network. We investigated whether ethanol influences the secretion of these cytokines using a co-culture model with keratinocytes from psoriatic patients (n = 9) or from healthy controls (n = 9), with HUT 78 lymphocytes, and determined the cytokine levels with or without ethanol treatment in the culture supernatants. TGF-alpha and IFN-gamma levels were elevated in the ethanol-treated psoriatic co-cultures, to 150% and 175% respectively, but neither in co-cultures with keratinocytes derived from healthy control individuals nor in monocultures. Treatment with ethanol elevated slightly the IL-6 levels in the monocultures from psoriatic and control keratinocytes to 125% but not in HUT 78 monocultures. In the psoriatic co-cultures, IL-6 levels were elevated in the culture supernatants to almost 160%, but they were not influenced by ethanol in co-cultures with control keratinocytes. The cytokine levels of IL-8 or IL-2 were not significantly influenced in the psoriatic mono- and co-cultures or in HUT 78 cultures. If ethanol influences the cytokine secretion of psoriatic keratinocytes and HUT 78 lymphocytes in co-culture conditions, these data suggest that ethanol could also influence the psoriatic cytokine network in vivo, which may explain the explain the aggravation of this disease in alcohol-consuming psoriatic patients.

Coculture Techniques↗
PubMed1995

Cyclosporin A, FK506 and dithranol after tyrosine-specific protein phosphorylation in HaCaT keratinocytes.

Protein tyrosine kinases (PTKs) are closely related to cell growth, proliferation and differentiation. In keratinocytes, various growth factor receptors and cytosolic proteins, including the EGF and IGF receptors, the proteins of the src family and others, exhibit PTK activity. In psoriatic epidermis an increased level of EGF receptors and their ligand TGF-alpha has been found, and this is thought to be one reason for the pathological hyperproliferation of keratinocytes in this disease. Oral treatment with cyclosporin A (CsA) and FK506 or topical treatment with dithranol lead to an improvement in psoriasis. In the present study we examined the effect of these three drugs on the cellular content of phosphorylated tyrosines in highly proliferative HaCaT keratinocytes. HaCaT keratinocytes can be used as a model for highly proliferative epidermis, e.g. psoriatic epidermis. CsA had no effect whereas FK506 and dithranol reduced the phosphorylation of tyrosine residues in HaCaT keratinocytes. The activation of serine/threonine protein kinase C (PKC) is known to downregulate PTKs. Therefore we incubated keratinocytes with the selective PKC inhibitor Ro 31-8220 in addition to the other drugs. Only after the addition of Ro 31-8220 to FK506-treated keratinocytes was the phosphotyrosine (p-tyr) level elevated, but this was only one-third of the increase measured without additional therapeutic drugs. We assume that an induction of PKC alone is not responsible for the reduced p-tyr level after treatment with dithranol and FK506.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthralin↗
PubMed1995

Ras gene mutations: a rare event in nonmetastatic primary malignant melanoma.

Ras gene mutations have been implicated in the pathogenesis of a variety of human tumors. Mutated ras genes have been isolated from human melanoma cell lines, but subsequent studies indicated that ras gene mutations may be a rare event in melanocytic lesions. Recently, a study reported a high frequency of ras mutations correlated with increasing invasion level. To address this inconsistency in the published data, we analyzed 50 primary melanomas to correlate invasion level, tumor thickness, histologic typing, and body localization with point mutations around codons 12/13/61 of the three ras genes. After micro-dissection of paraffin-embedded tumor tissue, ras gene mutations were analyzed by direct sequencing of tumor DNA amplified by polymerase chain reaction. Only two melanomas exhibited ras gene mutations, one sample containing a transition from A to G at position 2 of N-ras codon 61 and the other exhibiting a transversion from C to A at position 1 and a transition from A to G at position 2 of N-ras codon 61. Both tumors were classified as Clark level IV, with a tumor thickness of 2.5 and 1.2 mm, respectively. Both were typed as superficial spreading melanoma and localized to intermittently sun-exposed body sites. The low frequency of ras mutations in malignant melanoma and the lack of ras mutations in melanoma samples from constantly sun-exposed body sites argue against the hypothesis of ras mutations as a marker of progression in malignant melanoma and the suggestion that ras mutations occur predominantly in melanomas from constantly sun-exposed body sites.

Base Sequence↗
PubMed1995

Tyrosine phosphorylation in psoriatic T cells is modulated by drugs that induce or improve psoriasis.

BACKGROUND: The induction of protein tyrosine kinases (PTKs) is known to be a key element in the activation of lymphocytes. OBJECTIVE: Because immunologic mechanisms are important in the pathogenesis of psoriasis, we examined the time course of tyrosine-phosphorylated proteins (p-tyr) as a marker for cellular PTK activity in phytohemagglutinin (PHA)-stimulated T cells of psoriatic patients and healthy controls. METHODS AND RESULTS: PHA-stimulated T cells from both groups expressed peaks of p-tyr after 15 min and 4 h. In T cells from psoriatics, the 15-min peak was smaller but the 4-hour peak reached an enormous maximum, which was 270% higher than the basic p-tyr value. PHA-stimulated T cells were additionally treated with psoriasis-provoking drugs (lithium, chloroquine, propranolol and ethanol) and the two immunosuppressive drugs cyclosporin A and FK 506. Lithium and propranolol were able to increase the p-tyr level after 15 min in PHA-stimulated T cells from psoriatics in contrast to controls. Chloroquine and ethanol did not have a significant effect on T cells of both groups. CsA markedly diminished the phosphorylation of intracellular tyrosines in T cells of psoriatics and controls, whereas FK 506 diminished the p-tyr level in controls only slightly. CONCLUSION: We have characterized important differences in p-tyr phosphorylation activities of psoriatic T cells compared to controls. This could be a hint to explain the known abnormalities of psoriatic T cells.

Adolescent↗
PubMed1993

Chloroquine stimulates the mitogen-driven lymphocyte proliferation in patients with psoriasis.

Chloroquine is known to exacerbate psoriasis. Since immunological stimuli are considered to be important for the pathogenesis of psoriasis, we compared the effects of chloroquine on cell-mediated immunity in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin (PHA)-induced uptake of 3H-thymidine to measure lymphocyte proliferation. Chloroquine was added to the cultures at concentrations ranging from 0.022 to 220 microM. We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (p < 0.002). The spontaneous blastogenesis in both controls and patients remained stable under chloroquine. In PHA-driven cultures in controls, 0.022-2.2 microM chloroquine had no effect, higher concentrations of the drug suppressed proliferation. In patients, 22 microM chloroquine surmounted the suppression of the PHA-induced proliferative response found in controls; moreover, 2.2-0.022 microM chloroquine increased lymphocyte proliferation by > 300% (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally stimulated by the addition of pharmacological doses of chloroquine.

Adult↗