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Thomas Bieber

Publications and source records attributed to Thomas Bieber.

At least 73 records · Page 4Linked to original sources
PubMed2003

Evidence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic donors.

While mast cells and basophils constitutively express the high-affinity IgE receptor (Fc epsilon RI), it is absent or weakly expressed on APCs from normal donors. Fc epsilon RI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about Fc epsilon RI regulation on APCs are scarce. We show that in all donors intracellular alpha chain of the Fc epsilon RI (Fc epsilon RI alpha) accumulates during DC differentiation from monocytes. However, expression of gamma chains of the Fc epsilon RI (Fc epsilon RI gamma), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface Fc epsilon RI (Fc epsilon RI(neg) DCs). In contrast, DCs from atopics express surface Fc epsilon RI (Fc epsilon RI(pos) DCs) and show significant Fc epsilon RI gamma expression, which can be coprecipitated with Fc epsilon RI alpha. In Fc epsilon RI(neg) DCs lacking Fc epsilon RI gamma, immature and core glycosylated Fc epsilon RI alpha accumulates in the endoplasmic reticulum. In Fc epsilon RI(pos) DCs expressing Fc epsilon RI gamma, an additional mature form of Fc epsilon RI alpha exhibiting complex glycosylation colocalizes with Fc epsilon RI gamma in the Golgi compartment. IgE binding sustains surface-expressed Fc epsilon RI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced Fc epsilon RI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of Fc epsilon RI gamma and is preserved by increased IgE levels.

Antigens↗
PubMed2002

Kinetics of gene induction after FcepsilonRI ligation of atopic monocytes identified by suppression subtractive hybridization.

The high-affinity receptor for IgE, FcepsilonRI, on APCs plays an important role in the initiation and chronicity of inflammatory atopic diseases. To understand the molecular regulation of FcepsilonRI-mediated processes, differentially expressed genes are of great interest to be identified. Suppression subtractive cDNA hybridization has been used to identify genes induced after FcepsilonRI stimulation on atopic monocytes. Overexpression of the identified genes was determined by semiquantitative RT-PCR analysis of transcripts from the tester (stimulated) and driver (unstimulated) monocytes. Results were confirmed and kinetics of the transcripts established using blood cells from additional atopics at 4 and 24 h of FcepsilonRI induction. The following sequences were identified: monocyte chemoattractant protein 1, macrophage-inflammatory protein 1beta, IL-6, beta(A) subunit of inhibin/activin, IFN-stimulated gene of 54 kDa, IL-1R antagonist, and kynurenine 3-monooxygenase. Chemokines are highly expressed during the early and late phase after FcepsilonRI cross-linking, whereas proinflammatory and differentiation stimuli rapidly decline after an initial overexpression. Kynurenine 3-monooxygenase, an enzyme involved in the degradation of the amino acid tryptophan, is significantly up-regulated during the late phase after 24 h of FcepsilonRI induction. These results demonstrate that the analysis of the profile of gene induction following activation of FcepsilonRI on atopic monocytes may reveal how these cells might participate in the regulation of atopic disorders.

Base Sequence↗
PubMed2002

FcepsilonRI induces the tryptophan degradation pathway involved in regulating T cell responses.

FcepsilonRI is suspected to play a pivotal role in the pathophysiology of atopic disorders such as atopic dermatitis. In search for genes differentially regulated by FcepsilonRI on APCs, a differential cDNA bank of receptor-stimulated and unstimulated monocytes was established. By means of suppression subtractive hybridization, we identified kynurenine 3-monooxygenase and subsequently indoleamine 2,3-dioxygenase (IDO) to be overexpressed in FcepsilonRI-activated monocytes. IDO is the rate-limiting enzyme in the catabolism of the essential amino acid tryptophan. We show that cross-linking of FcepsilonRI on monocytes results in low tryptophan concentrations associated with impaired T cell stimulatory capacity. Importantly, T cell suppression could be prevented by the addition of tryptophan or inhibition of IDO. Moreover, stimulation of T cells by FcepsilonRI-activated monocytes was increased compared with T cell stimulation by nonactivated monocytes if exogenous supply of tryptophan was available. We speculate that the expression of IDO by FcepsilonRI(+) APCs in vivo allows these cells to regulate T cell responses in atopic disorders by inhibiting or stimulating T cell proliferation, depending on the metabolic environment.

Antigen-Presenting Cells↗
PubMed2002

A reducing microenvironment leads to the generation of FcepsilonRIhigh inflammatory dendritic epidermal cells (IDEC).

Inflammatory dendritic epidermal cells present in skin lesions of the atopic eczema/dermatitis syndrome display the highest expression of the high-affinity receptor for IgE (FcepsilonRI), ever detected on human antigen-presenting cells. Owing to the instability of the FcepsilonRI (alphagammagamma) complex and fast cleavage from the cell surface during the interleukin-4/granulocyte-macrophage colony-stimulating factor driven in vitro differentiation of monocytes, a method to generate inflammatory dendritic epidermal cells was not at our disposal in the past and the amount of ex vivo isolated inflammatory dendritic epidermal cells available for functional assays was limited. Therefore, information about the role of inflammatory dendritic epidermal cells and FcepsilonRI on this dendritic cell subtype in atopic and inflammatory skin diseases is completely missing. In this study, we were able to: (i) increase the expression of a functional FcepsilonRI complex on the cell surface of immature monocyte-derived dendritic cells from atopic donors by creating a reducing microenvironment; (ii) enhance significantly the intracellular pool of the FcepsilonRIgamma chains, which is the limiting parameter for the FcepsilonRI surface expression; and (iii) generate monocyte-derived dendritic cells displaying the phenotypical characteristics of inflammatory dendritic epidermal cells, producing high amounts of proinflammatory cytokines and chemokines similar to the cytokines found in lesional skin of the atopic eczema/dermatitis syndrome. Altogether the high expression of functional FcepsilonRI on these cells enables us for the first time to study inflammatory dendritic epidermal cells and FcepsilonRI-mediated mechanisms of inflammatory dendritic epidermal cells in vitro, in order to shed light on the putative role of this important cell type in the atopic eczema/dermatitis syndrome.

Cells, Cultured↗
PubMed2002

Dichotomic nature of atopic dermatitis reflected by combined analysis of monocyte immunophenotyping and single nucleotide polymorphisms of the interleukin-4/interleukin-13 receptor gene: the dichotomy of extrinsic and intrinsic atopic dermatitis.

Patients with atopic dermatitis display substantial immunologic abnormalities, among which elevated total IgE is considered as a hallmark; however, a subgroup of atopic dermatitis patients exhibits normal IgE levels, but mechanisms contributing to the so-called "intrinsic" or "nonallergic" form of atopic dermatitis are obscure. In order to unravel similarities and differences of both atopic dermatitis subtypes, the phenotype of monocytes, total serum IgE levels, and serum levels of cytokines regulating the IgE production from nonatopic individuals and patients with allergic rhinitis, and extrinsic and intrinsic atopic dermatitis were measured. Concomitantly, genomic DNA probes of all subjects were analyzed for single nucleotide polymorphisms of candidate genes of structures involved in the regulation of the IgE synthesis, such as interleukin-4 and the interleukin-4R/interleukin-13R. Our data show that the surface expression of the high- and low-affinity receptor for IgE (FcepsilonRI and FcepsilonRII/CD23) and the interleukin-4Ralpha chain were significantly elevated in monocytes from patients with extrinsic atopic dermatitis. Furthermore, serum levels of interleukin-13 were significantly increased in patients with intrinsic atopic dermatitis. In addition, the frequency of the interleukin-4Ralpha polymorphism C3223T and the interleukin-4 polymorphism C590T tended to be higher in extrinsic atopic dermatitis than in intrinsic atopic dermatitis. Altogether our findings indicate that intrinsic atopic dermatitis patients exhibit phenotypic and immunologic features, which differ from those of patients with extrinsic atopic dermatitis or other atopic disorders.

Adolescent↗
PubMed2002

Enhanced expression and activity of protein-tyrosine kinases establishes a functional signaling pathway only in FcepsilonRIhigh Langerhans cells from atopic individuals.

The trimeric high-affinity IgE receptor (FcepsilonRI) on human epidermal Langerhans cells mediates IgE-dependent antigen uptake and subsequent antigen focusing. Its expression is upregulated on Langerhans cells (FcepsilonRIhigh Langerhans cells) and inflammatory dendritic epidermal cells (FcepsilonRIhigh inflammatory dendritic epidermal cells) in the skin of patients with atopic dermatitis. In the absence of the amplifying beta-chain in these cells, FcepsilonRI signaling (indicated by calcium mobilization and activation of the transcription factor nuclear factor-kappaB) is only detectable in FcepsilonRIhigh Langerhans cells from atopics, but not FcepsilonRIlow Langerhans cells from nonatopics. Therefore we investigated protein-tyrosine kinases putatively involved in FcepsilonRI signaling in Langerhans cells and asked whether differences in their expression and FcepsilonRI-induced activity could explain the dichotomic responses observed in atopic vs nonatopic individuals. First, we found the src protein-tyrosine kinases p53/56lyn, p59fyn, p56/59hck, p55c-fgr, and p60c-src to be expressed in Langerhans cells from all donors. In addition, whereas p56lck was lacking, p72syk and the negative regulatory p50csk were detected. Upon terminal maturation of Langerhans cells in vitro, no significant change of the protein- tyrosine kinase expression profile except downregulation of p56/59hck was observed. In contrast, significant upregulation of all protein-tyrosine kinase expressed except p50csk was detected in FcepsilonRIhigh Langerhans cells, but not in FcepsilonRIhigh inflammatory dendritic epidermal cells. Finally, the important protein-tyrosine kinases substrate phospholipase C-gamma1, which is also essential for downstream calcium mobilization, was only phosphorylated upon FcepsilonRI triggering in FcepsilonRIhigh Langerhans cells from atopics, but not in FcepsilonRIlow Langerhans cells from nonatopics. Therefore, upregulation of FcepsilonRI and protein-tyrosine kinase expression as well as subsequent protein-tyrosine kinase activity may explain, at least in part, that an efficient signaling pathway in terms of calcium mobilization is restricted to FcepsilonRIhigh Langerhans cells from atopic individuals. Key words:

Cell Line↗
PubMed2002

Aggregation of the high-affinity IgE receptor Fc(epsilon)RI on human monocytes and dendritic cells induces NF-kappaB activation.

In contrast to mast cells and basophils, the high-affinity IgE receptor (Fc(epsilon)RI) on monocytes and dendritic cells (DC), including epidermal Langerhans cells, is not constitutively expressed and lacks the beta-chain. Fc(epsilon)RI is upregulated on Langerhans cells of atopic individuals, particularly in atopic dermatitis skin. Although Fc(epsilon)RI provides IgE-mediated antigen focusing on monocytes and DC/Langerhans cells, its relevance for cell activation remains elusive, and the transcription factors regulating Fc(epsilon)RI-induced genes are unknown. We show that NF-kappaB, known to regulate genes essential for inflammatory responses and DC differentiation and function, is activated upon Fc(epsilon)RI ligation in primary human monocytes and DC. In Langerhans cells isolated from epidermis, NF-kappaB activation is restricted to donors expressing high Fc(epsilon)RI amounts. Fc(epsilon)RI-induced NF-kappaB complexes in monocytes and DC contain p50 and p65, but no other NF-kappaB subunits despite increased RelB expression during differentiation. NF-kappaB activation is preceded by serine phosphorylation and degradation of its inhibitory protein IkappaB-alpha without involving other IkappaB proteins. Finally, we show that Fc(epsilon)RI ligation on monocytes and DC leads to synthesis and release of tumor necrosis factor-alpha and monocyte chemoattractant protein-1, which is decreased by two mechanistically distinct inhibitors of NF-kappaB activation. Thus NF-kappaB activation represents a novel mechanism by which Fc(epsilon)RI on monocytes and DC potentially controls inflammatory reactions.

Antibodies, Anti-Idiotypic↗
PubMed2002

Successful treatment of Dowling-Degos disease with Er:YAG laser.

BACKGROUND: Dowling-Degos disease is a rare condition with a genetically determined disturbance of epidermal proliferation. The typical clinical picture is a reticulate pigmentation of the flexures, genital folds, and pectoral skin areas. Many different treatment options have been tried in recent years without a convincing therapeutic benefit. OBJECTIVE: To determine the effectiveness of Er:YAG laser in Dowling-Degos disease. METHODS: A 44-year-old woman suffering from Dowling-Degos disease was treated with the Er:YAG laser pulse energy between 1,000 and 1,200 mJ, three consecutive passes. RESULTS: The laser treatment led to a good clinical result. CONCLUSION: Our case suggest that treatment with the Er:YAG laser might be a successful strategy in Dowling-Degos disease.

Adult↗
PubMed2002

Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone butyrate ointment in adult patients with atopic dermatitis.

BACKGROUND: Vehicle-controlled studies have demonstrated the efficacy and safety of tacrolimus ointment for patients with atopic dermatitis. OBJECTIVE: This study was undertaken to compare 0.03% and 0.1% tacrolimus ointment with 0.1% hydrocortisone-17-butyrate ointment, a midpotent to potent topical corticosteroid, in the treatment of adult patients with moderate-to-severe atopic dermatitis. METHODS: Patients applied ointment twice daily to all affected areas for 3 weeks in this multicenter, randomized, double-blind, parallel-group study. The primary endpoint was the modified eczema area and severity index (mEASI) mean area under the curve as a percentage of baseline. RESULTS: Five hundred seventy patients were randomized and received treatment. Discontinuations included 22 of 193 patients from the 0.03% tacrolimus group, 22 of 191 patients from the 0.1% tacrolimus group, and 17 of 186 patients from the hydrocortisone butyrate group. The median mEASI mean area under the curve as a percentage of baseline was 47.0%, 36.5%, and 36.1% for patients who received 0.03% tacrolimus, 0.1% tacrolimus, and 0.1% hydrocortisone butyrate, respectively. There was no statistically significant difference between 0.1% tacrolimus and 0.1% hydrocortisone butyrate; however, the lower improvement in mEASI for 0.03% tacrolimus was statistically significant when compared with 0.1% tacrolimus (P <.001) or hydrocortisone butyrate (P =.002). Skin burning and pruritus at the application site showed a higher incidence in the tacrolimus treatment groups than in the hydrocortisone butyrate group (P <.05). Laboratory parameters showed no treatment differences and no marked changes over time. CONCLUSIONS: The efficacy of 0.1% tacrolimus ointment was similar to that of 0.1% hydrocortisone butyrate ointment and was lower for 0.03% tacrolimus ointment. No serious safety concerns were identified.

Administration, Topical↗
PubMed2002

House dust mite allergen levels in German day-care centers.

We investigated the levels of the major house dust mite allergens, Der p 1 and Der f 1, in dust collected from various locations in 41 day-care centers from two German cities (Düsseldorf and Bonn). One hundred and thirty-seven (96%) of 143 samples yielded detectable amounts of house dust mite allergen (range, < 15-85,000 ng/g; interquartile range, 210-1,480 ng group I allergen [sum of Der p 1 and Der f 1]/g dust), and 24 (17%) of the samples (8/34 mattresses; 11/46 cushions/soft toys; 5/43 carpeted floors, 0/20 smooth floors) exceeded the proposed "threshold" level of 2,000 ng/g dust in 18 (44%) of 41 day-care centers. Der p 1 and Der f 1 could be detected in nearly an equal number of samples. The highest concentrations of house dust mite allergens were found in dust from mattresses (geometric mean, 1,103 ng/g dust) and cushions/soft toys (geometric mean, 1,004 ng/g dust). The allergen load per unit area from carpeted floors exceeded that from smooth floors by more than two orders of magnitude. In comparison with dust samples from private homes within the same geographical area, the mite allergen levels in mattress dust (RR, 0.34; CI95, 0.18-0.64) and floor dust (RR, 0.21; CI95, 0.09-0.49) from day-care centers were significantly lower (p < 0.001). We conclude that day-care centers should be included as potential places of additional exposure to house dust mite allergens if avoidance measures are taken.

Allergens↗
PubMed2002

New diagnostic classification of allergic skin disorders.

PURPOSE OF REVIEW: To highlight the importance of one common nomenclature for allergic skin disorders. RECENT FINDINGS: Diseases are best defined on the pathophysiological mechanisms underlying the symptoms. Although the mechanisms behind what is sometimes unfortunately referred to as 'atopic eczema' or 'atopic dermatitis' have been quite well understood for 30 years the present terms used are confusing. Over the years more than 20 different names have been used. SUMMARY: Doctors, scientists and patients in the field of allergy must use one and the same terminology for allergic diseases or the result will be confusion. Diagnosis, prevention, treatment, patient advice, environmental relations, and the search for genetic markers are examples of areas that will be hampered by conflicting results. Strong efforts should be invested into broadly implementing the European Academy of Allergology and Clinical Immunology (EAACI) revised nomenclature for allergy.

Allergens↗
PubMed2002

Benign neonatal hemangiomatosis in a pre-term infant.

Benign neonatal hemangiomatosis (BNH) is a condition of multiple neonatal strawberry hemangiomas limited to the skin. Characteristically, a rapid proliferative growth phase is followed by a prolonged involutional phase. Regression of cutaneous lesions usually starts in the fourth month, but variations until complete involution are high for individial lesions. Disseminated neonatal hemangiomatosis (DNH) represents a serious multisystemic disorder with hemangiomas in different organs and the skin. Early evaluation of the patients and treatment of visceral hemangiomas is of crucial importance. While solitary hemangiomas have been reported to occur more commonly in pre-term infants, prematurity has rarely been described in the literature as being associated with BNH.

Female↗
PubMed2002

Topical treatment of pyoderma gangraenosum.

The treatment of pyoderma gangraenosum (PG) is still a therapeutic challenge. Although several drugs such as corticosteroids, dapsone, clofazimine, azathioprine, tacrolimus and cyclosporine A have been shown to be effective in this disease, side-effects of these agents limit their systemic use in seriously ill patients. In recent years, topical treatment of the disease has gained attention. Several reports show an improvement of cutaneous lesions of PG following topical treatment. These earlier reports as well as our own observations suggest that topical therapeutic regimens can be a useful and safe alternative to systemic immunosuppressive therapy in the treatment of PG. We give a review about these topically used drugs and the mechanisms probably involved.

Administration, Cutaneous↗
PubMedDate not supplied

DRESS syndrome associated with carbamazepine and phenytoin.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome reflects a serious hypersensitivity reaction to drugs. Its clinical manifestations include diffuse maculopapular rash, exfoliative dermatitis, facial edema, lymphadenopathy, fever, multivisceral involvement and it is associated with a high mortality rate. We report a 62-year-old patient suffering from epilepsia presenting erythroderma following carbamazepine intake. Blood tests revealed eosinophilia, leukocytosis, elevated liver enzymes and high levels of Eosinophil Cationic Protein (ECP). We applied systemic steroids and anticonvulsant therapy was switched to phenytoin, which had been taken previously without adverse reactions. The skin eruptions persisted and the patient developed fever. Anticonvulsant medication was discontinued and skin eruptions finally resolved under steroid application. This case report demonstrates that cross reactivity between carbamazepine and phenytoin may not only lead to the development but also to the worsening of DRESS syndrome. ECP blood levels may represent a sufficient parameter to monitor the development of DRESS syndrome.

Anticonvulsants↗