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Biomedical subjects

T Bieber

Publications and source records attributed to T Bieber.

At least 91 records · Page 5Linked to original sources
PubMed2000

Atopic dermatitis: pathogenetic mechanisms.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing incidence and socio-economical relevance. The diagnosis is made on clinical grounds and different diagnostic criteria sets have been established. The majority of all AD cases is associated with a sensitization to environmental allergens and increased serum IgE (so-called extrinsic AD), but about 10--30% of all cases suffer from the so-called intrinsic AD, which obviously lacks any link to the classical atopic diathesis. The genetic background of AD has been investigated by target gene approach by different groups with mostly contradictory results for each of the genes under study. An imbalance in the spectrum of Th1/Th2 responses, a disturbed prostaglandin metabolism, intrinsic defects in keratinocyte function, delayed eosinophil apoptosis, IgE-mediated facilitated antigen presentation by epidermal dendritic cells, a two phase model of the inflammatory response and staphylococcal superantigen effects are among the currently studied pathogenetical aspects of extrinsic AD, which are reviewed in this paper.

Dermatitis, Atopic↗
PubMed2000

The high-affinity IgE receptor (FcepsilonRI) blocks apoptosis in normal human monocytes.

Monocytes have a limited life span, and their homeostasis is regulated by apoptosis in vivo. When cultured in the absence of appropriate exogenous stimuli, they undergo apoptosis, but under the influence of survival signals, these cells differentiate into macrophages or dendritic cells. Here we show that ligation of the high-affinity IgE receptor (FcepsilonRI) on human monocytes from nonatopic individuals markedly reduces apoptosis induced by serum deprivation or by CD95/Fas ligation. Aggregation of FcepsilonRI reduces its own expression but fails to modulate CD95/Fas expression. In contrast, FcepsilonRI ligation enhances the expression of the antiapoptotic molecules Bcl-2 and Bcl-xL, but not Mcl-1, in monocytes. Incubation of unstimulated cells with culture supernatants of FcepsilonRI-activated monocytes prolongs their life span, whereas CD95/Fas expression remains unaffected. The incidence of apoptosis is restored considerably when the supernatant is depleted of TNF-alpha, whereas elimination of IL-1beta, GM-CSF, or IL-12 has no effect. These results indicate that FcepsilonRI mediates signals preventing monocyte apoptosis directly by increasing the levels of Bcl-2 and Bcl-xL, and indirectly by means of TNF-alpha in an autocrine and paracrine fashion. This process may contribute to the establishment of chronic allergic disorders such as atopic dermatitis.

Antibodies, Monoclonal↗
PubMed1999

Phenotyping of epidermal dendritic cells: clinical applications of a flow cytometric micromethod.

BACKGROUND: The differential diagnosis of inflammatory skin diseases is largely based on the patient's history and the morphological analysis of the skin lesion. Laboratory data, such as serum IgE-level and prick and patch tests, may be helpful but do not assess individual lesions. The assumption of our approach is that each individual lesion is associated with a specific microenvironment and that the immunophenotype of the two epidermal dendritic cell populations, Langerhans cells (LC) and inflammatory dendritic epidermal cells (IDEC), reflects this environment in a disease-specific manner. METHODS: A flow cytometric micromethod was developed to directly analyze individual inflammatory human skin lesions. Crude epidermal single cell suspensions were prepared by trypsinization, stained for three-color analysis with different monoclonal antibodies and the vital stain 7-amino-actinomycin-D, and finally analyzed on a single laser equipped FACScan flow cytometer. RESULTS: With a limited set of cell surface markers, such as FcepsilonRI, FcgammaRII/CD32, CD1b and CD36, highly specific diagnostic criteria for atopic dermatitis and inflamed human skin could be established. CONCLUSIONS: Phenotyping of epidermal dendritic cells is a useful procedure helpful in differential diagnosis of inflammatory skin diseases.

Antigens, CD1↗
PubMed1999

[Successful therapy of an ILVEN in a 7-year-old girl with calcipotriol].

A 7-year-old otherwise healthy girl presented with a 2-year history of an ILVEN (inflammatory linear verrucous epidermal nevus) located on the inner part of her right upper arm. The diagnosis was histologically confirmed. Different conservative therapeutic strategies with corticosteroids, antibiotics and antimycotics produced little or no improvement. Because of encouraging reports describing the successful use of 0.005% calcipotriol ointment in patients with ILVEN, we treated our patient with this regimen. After 4 weeks we could recognize a impressive improvement and after 8 weeks the ILVEN had nearly completely disappeared. 25 weeks after withdrawal of calcipotriol, no relapse had occurred. The dramatic response to calcipotriol suggests some pathological links between ILVEN and psoriasis.

Administration, Topical↗
PubMed1999

A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity.

PURPOSE: Low molecular weight branched polyethylenimine (LMW-PEI) was synthesized and studied as a DNA carrier for gene delivery with regard to physico-chemical properties, cytotoxicity, and transfection efficiency. METHODS: The architecture of LMW-PEI, synthesized by acid catalyzed ring-opening polymerization of aziridine was characterized by size exclusion chromatography in combination with laser light scattering and 13C-NMR-spectroscopy. In vitro cytotoxic effects were quantified by LDH and MTT assay and visualized by transmission electron microscopy. The potential for transgene expression was monitored in ECV304 cells using luciferase driven by a SV40 promotor as reporter gene system. RESULTS: LMW-PEI (Mw 11'900 D) with a low degree of branching was synthesized as a DNA carrier for gene delivery. In contrast to high molecular weight polyethylenimines (HMW-PEI; Mw 1'616'000 D), the polymer described here showed a different degree of branching and was less cytotoxic in a broad range of concentrations. As demonstrated by transmission electron microscopy the LMW-PEI formed only small aggregates which were efficiently taken up by different cells in the presence of serum, most likely by an endocytic pathway. LMW-PEI yielded transfection efficiencies measured via expression of the reporter gene luciferase which were up to two orders of magnitude higher than those obtained with HMW-PEI. The reporter gene expression was concentration dependent, but in contrast to lipofection independent of serum addition. CONCLUSIONS: The LMW-PEI described here is a new, highly efficient, and non-cytotoxic vector with a favorable efficiency/toxicity profile for gene therapeutic applications.

Animals↗
PubMed1999

Annular erythema caused by impending pacemaker extrusion.

A 72-year-old patient with an implanted cardiac pacemaker presented with a circumscribed erythematous area on his chest. It was only several months later, after he had developed positional, localized pain in this area, that the diagnosis of an impending pacemaker extrusion became evident. This case illustrates the diagnostic difficulties in patients with pacemaker-associated skin lesions. Regular follow-up examinations and close co-operation of dermatologists, cardiologists and cardiothoracic surgeons are of major importance in view of the potentially life-threatening complications.

Aged↗
PubMed1999

Unilateral linear lichen planus with mucous membrane involvement.

Linear lichen planus is a rare distinctive variant of lichen planus (LP) characterized by a pruritic eruption of lichenoid, violaceous papules in a linear distribution that sometimes assume a Blaschko line pattern. We describe a 33-year-old woman who presented with a 4-month history of a slightly pruritic unilateral linear array of papular lesions on the left side of her neck that were clinically and histologically consistent with linear LP. Two months after the onset of her skin disease she developed typical lesions with a lacy white pattern on the left lateral aspect of her tongue and the left buccal mucosa with a striking predominance for the left side. Clinically the lesions on the patient's neck were similar to lichen striatus or lichenoid epidermal naevus, a variant of linear verrucous epidermal naevus. However, the histological features and the fact that later in the course of her disease the patient developed typical LP of the oral mucosa suggest that this patient has the rare condition of linear LP with unilateral restriction.

Adult↗
PubMed1999

Embolia cutis medicamentosa of the foot after sclerotherapy.

Typically, embolia cutis medicamentosa is reported after intramuscular injections of drugs. We describe a case of embolia cutis medicamentosa after sclerotherapy of intracutaneous veins of the foot with a polidocanol solution of 1%. Under therapy with intravenous alprostadil, pentoxifyllin, internal steroids and anticoagulation with heparin, the lesions healed completely without necrosis.

Aged↗
PubMed1998

Regulation of the high affinity receptor for IgE on human epidermal Langerhans cells.

Human epidermal Langerhans cells (LC) express variable amounts of the high affinity receptor for IgE (Fc epsilonRI); the strongest expression is characteristic of atopic dermatitis. The receptor is suggested to take part in the pathophysiology of this disease by acting as a link between aeroallergens and Ag-specific T cells in an IgE-mediated, delayed-type hypersensitivity reaction. In the present study we show that even in the absence of surface expression, normal LC maintain an intracellular pool of the alpha-chain of Fc epsilonRI (Fc epsilonRIalpha) of the same m.w. as the surface-bound Fc epsilonRIalpha that is able to bind significant amounts of IgE. The lack of surface expression is linked to the absence or very low expression of the gamma-chain (Fc epsilonRIgamma). Moreover, the amount of Fc epsilonRIalpha expressed at the cell surface significantly correlates with the amount of Fc epsilonRIgamma. LC differentiation toward lymphoid dendritic cells is accompanied by the disappearance of transcripts for Fc epsilonRIalpha, but not for Fc epsilonRIgamma. This leads to a rapid decrease in the intracellular and surface levels of Fc epsilonRIalpha, which cannot be influenced by IL-4, IgE, or other agents. Overall, our findings suggest that these mechanisms enable LC to be highly versatile APCs by rapidly adapting the surface level of Fc epsilonRI to distinct inflammatory environments.

Cell Differentiation↗
PubMed1998

5-Lipoxygenase expression in Langerhans cells of normal human epidermis.

We studied expression of the 5-lipoxygenase (5-LO) pathway in normal human skin. In situ hybridization revealed a 5-LO mRNA-containing epidermal cell (EC) population that was predominantly located in the midportion of the spinous layer, in outer hair root sheaths, and in the epithelial compartment of sebaceous glands. Examination of skin specimens by immunohistochemistry and of primary ECs by flow cytometry mapped the 5-LO protein exclusively to Langerhans cells (LCs). The LC 5-LO protein was largely found in the nuclear matrix, in nuclear envelopes, and perinuclear regions as indicated by in situ confocal laser scan microscopy. Reverse transcription-PCR and immunoblot analyses of purified primary EC populations further indicated that LCs are major 5-LO expressing cells. Enriched primary LCs were also found to contain 5-LO activating protein (FLAP), leukotriene (LT) C4 synthase, and LTA4 hydrolase. By contrast, 5-LO, FLAP, and LTC4 synthase were undetectable or largely reduced, but LTA4 hydrolase transcripts and protein were identified in ECs depleted of LCs. These data show that naive LCs are major, and possibly the sole, 5-LO pathway expressing cells in the normal human epidermis.

Arachidonate 5-Lipoxygenase↗
PubMed1998

IL-10 inhibits ICAM-1 expression on human Langerhans cells but not on keratinocytes, dermal endothelial cells or fibroblasts.

Intercellular adhesion molecule-1 (ICAM-1) is regularly expressed or inducible on all major cutaneous cell populations including Langerhans cells, keratinocytes, endothelial cells and dermal fibroblasts. ICAM-1 is induced in the skin under inflammatory conditions and plays an important role in the activation of T cells. Interleukin-10 (IL-10) is a pluripotent immunosuppressive cytokine that inhibits proliferation of T cells via inhibition of antigen-presenting cells including Langerhans cells. We demonstrates that IL-10 inhibits baseline and also cytokine-stimulated ICAM-1 expression on human Langerhans cells, which has previously been shown in the murine system. No effect of IL-10 was seen on human dermal vascular endothelial cells, which like Langerhans cells are also able to present antigen. Additionally, no inhibitory effect of IL-10 was observed on the ICAM-1 expression of keratinocytes and dermal fibroblasts. As IL-10 only weakly suppresses MCH II on human Langerhans cells, inhibition of ICAM-1 and other accessory molecules by IL-10 seems to be an important mechanism inhibiting the antigen-presenting function of human Langerhans cells.

Dermis↗