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Biomedical subjects

T Bieber

Publications and source records attributed to T Bieber.

At least 37 records · Page 2Linked to original sources

Invasive chromoblastomycosis and sinusitis due to Phialophora verrucosa in a child from northern Africa.

We report on a severe, verrucous facial mycosis and sinusitis in a 12-year-old Libyan girl. Her disease started with verrucous, hyperkeratotic plaques and subcutaneous violet nodules of unknown origin on her face and upper extremities. Despite topical antimycotic therapy she needed in-hospital treatment because of severely progressive tumorous cutaneous and nasal lesions. Microscopic examination of scale samples taken from the upper extremities and the face revealed brown, thick-walled fungal elements. Under the assumption of a chromoblastomycosis, an oral treatment with itraconazole and fluorocytosin was initiated, with significant improvement of the lesions. The aetiological agent was identified as Phialophora verrucosa.

Antifungal Agents↗

Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study.

PURPOSE: To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma. PATIENTS AND METHODS: Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days). RESULTS: Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n=229; 15.2% v 6.8%; P=.043) and in full analysis set (n=221) (15.5% v 7.2%; P=.053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P=.059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P=.067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms. CONCLUSION: ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.

Adult↗

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies.

It has been repeatedly demonstrated that allergic reactions are driven by the continuous flow of antigen uptake and presentation processes, which are perpetuated mainly by dendritic cells (DC). The ability of allergens to cause allergic inflammation is contingent upon the presence of an immunological milieu and microenvironment that either privileges Th2 responses or prohibits these reactions by the induction of contraregulatory anti-inflammatory activities of the immune system. In the light of recent developments it appears that DC have to manage two opposing tasks: on the one hand they can favor pro-inflammatory reactions and actively induce a T-cell response, yet on the other hand they serve an important function as 'silencers' in the immune system by sending out anti-inflammatory, tolerance inducing signals. This unique capacity of DC has opened several exciting possibilities for a role of DC in both - accelerating and slowing down allergic reactions. It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity.

Allergens↗

Lymphocytopenia in lupus erythematosus: close in vivo association to autoantibodies targeting nuclear antigens.

BACKGROUND: Leukopenia and lymphopenia are typical features of lupus erythematosus (LE) and correlate with elevated disease activity and higher grades of systemic involvement. Antilymphocyte antibodies are regarded as the most likely rationale for the decreased cell numbers; however, their relevance has not been confirmed so far. OBJECTIVES: Previous investigations at our department have shown a significant correlation between diminished lymphocyte numbers and the presence of antinuclear antibodies (ANA). We wanted to achieve a better understanding of this phenomenon. METHODS: We performed a detailed analysis of autoantibodies and peripheral leucocyte subsets in 82 patients with different subtypes of LE. Leucocyte subsets were measured using flow cytometry (FACScan; Becton Dickinson, Franklin Lakes, NJ, USA.); autoantibodies were detected by indirect immunofluorescence and by enzyme-linked immunosorbent assay. RESULTS: A significant association (P < 0.05) between specific antibodies targeting nuclear antigens (SSA/Ro-52, SSB/La, snRNPs) and lymphocytopenia was found. CONCLUSIONS: We suppose that some of these autoantibodies might have an antilymphocyte effect. Apoptosis induction by specific antinuclear antibodies has already been described earlier, but to the best of our knowledge this is the first study presenting a strong indication of a possible interaction between these antibodies and lymphocyte subsets in vivo.

Adolescent↗

Successful treatment of acrodermatitis continua suppurativa with topical tacrolimus 0.1% ointment.

Acrodermatitis continua suppurativa of Hallopeau (ACS) is a rare pustular variant of psoriasis in which numerous treatment modalities have been used without any consistent long-term effect. We report for the first time two patients with ACS which was successfully treated with topical tacrolimus 0.1% ointment. Our observations raise hopes that this new treatment strategy for ACS may constitute a novel effective therapeutic option for this recalcitrant condition.

Acrodermatitis↗

Asymptomatic atopy is associated with increased indoleamine 2,3-dioxygenase activity and interleukin-10 production during seasonal allergen exposure.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan (TRP)-catabolizing enzyme with regulatory effects on T cells. T cell inhibition is achieved through both TRP depletion and TRP metabolite accumulation in specific local tissue microenvironments. The expression of IDO activity by different types of antigen-presenting cells (APCs) has been shown to play a role in many instances of immunoregulation and tolerance induction. Induction of IDO after the engagement of the high-affinity receptor for IgE, FcepsilonRI, on atopic monocytes has been suggested to regulate T cell responses in atopic disorders. Interleukin-10 (IL-10), a cytokine known for its down-regulatory functions in the immune system, has recently been associated with the stable expression of IDO in mature tolerogenic dendritic cells. OBJECTIVE: This study was devised to understand the role of systemic IDO and IL-10 in the prevention of clinical apparent allergy. METHODS: The concentration of TRP and the break-down product kynurenine were measured by high-performance liquid chromatography in- and off-season in sera from patients with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic patients sensitized to specific aeroallergens (n=12). Non-atopic (NA) individuals (n=12) served as control. The concentration of plasma IL-10 was determined in parallel from these donors by ELISA in- and off-season. RESULTS: In clinically unresponsive but aeroallergen-sensitized atopic individuals significantly higher systemic activity of IDO and increased plasma IL-10 levels were found during allergen exposure but not off-season compared to symptomatic atopic individuals with allergic rhinitis and NA individuals. CONCLUSION: Enhanced systemic IDO activity as well as increased systemic levels of IL-10 may contribute to the containment of allergic T cell responses and could be involved in the maintenance of a state of clinical unresponsiveness.

Adult↗

Comparative immunophenotyping of monocytes from symptomatic and asymptomatic atopic individuals.

BACKGROUND: Allergy has at least two components - a genetic predisposition referred to as atopy and the progress from an atopic state to clinically apparent disease. Peripheral blood monocytes are circulating myeloid precursors of antigen-presenting cells. The expression of cell surface proteins on monocytes may therefore witness the disease status and affect the development of allergic disease. METHODS: Monocytes were isolated from atopic individuals with seasonal allergic rhinitis (n = 10), from atopic individuals sensitized to aeroallergens but without any signs of acute disease (n = 11), and from healthy nonatopic donors (n = 21). Detailed comparative phenotypic analysis of CD14(+) and FcepsilonRI(+)CD14(+) monocytes was performed by flow cytometry. RESULTS: CD14(+) monocytes from symptomatic atopic donors showed a significant increase in the cell surface intensity of the integrin adhesion molecule CD11c over monocytes from asymptomatic atopic and nonatopic donors. Asymptomatic atopic individuals showed significantly enhanced expression of FcepsilonRI on the CD14(high)CD16(dim) monocyte subset compared with this subset from symptomatic atopic and nonatopic donors. CONCLUSION: The increase in monocyte surface intensity of the adhesion molecule CD11c may be involved in the manifestation of allergic disease. FcepsilonRI on CD14(high)CD16(dim) monocytes of asymptomatic atopic donors may be of functional importance for the maintenance of clinical unresponsiveness toward allergens.

Adult↗

Limited reliability of E-cadherin as a specific marker for in vitro-generated Langerhans cells.

Langerhans cells (LC) are a unique population of dendritic cells (DC) found in the epidermis where they can be identified by the expression of CD1a, E-cadherin and cytoplasmic Birbeck granules (BG) as their hallmark. Over the past years many techniques have been described to generate LC in vitro from either monocytes or CD34(+) hematopoietic cell progenitors. Antibodies against Lag and Langerin (two epitopes associated with BG) and E-cadherin (a Ca(2+)-dependent homophilic adhesion molecule) have been used to detect in vitro-generated LC. In this study we investigated whether the expression of E-cadherin on in vitro-generated CD1a(+) from either CD34(+) cells or monocytes is able to discriminate LC from other DC. Our results demonstrate that E-cadherin alone is not a reliable marker to specifically identify in vitro-generated LC.

Antigens, CD↗

Safety of rush insect venom immunotherapy. The results of a retrospective study in 178 patients.

BACKGROUND: Venom immunotherapy (VIT) is regarded as an established and efficient treatment of Hymenoptera venom allergy. Different frequencies of side-effects have been reported in the literature, depending on the hyposensitization regimen (conventional outpatient programme, rush immunotherapy, ultra rush immunotherapy) and the venom preparation. Aim of this study was to evaluate safety and tolerance of rush VIT in patients treated with a 7-day protocol in our department. METHODS: VIT protocols of 178 patients treated at the Department of Dermatology and Allergy of the University of Bonn were analysed retrospectively. All patients had been treated with a standardized venom preparations (ALK-SQ). We used a modified VIT-protocol with a 2-day break to reduce systemic side-effects. RESULTS: During the course of VIT in 15 patients (8.4%) systemic reactions grade I (Mueller scale) were observed, in seven (3.9%) grade II, in six (3.4%) grade III and in four (2.2%) grade IV. A total of 146 patients (82.1%) had no or only local reactions. CONCLUSIONS: The rate of systemic adverse reactions Mueller Grade I-IV of 17.9% of the 'Bonn rush VIT protocol' appears to be relatively low compared with the data in the literature.

Adolescent↗

New treatment modalities for granuloma faciale.

Granuloma faciale (GF) is a rare, chronic skin disorder in which numerous treatment modalities have been used without any consistent long-term effect. We report three cases of GF, two of which were successfully treated with the Laserscope potassium-titanyl-phosphate 532-nm laser within 2 weeks and one with topical tacrolimus ointment 0.1%. Our observations suggest that these new treatment modalities for GF, which we report here for the first time, can provide effective and non-invasive treatment for this disease.

Aged↗

The central role of FcepsilonRI in allergy.

The high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, plays a central role in the initiation and control of atopic allergic inflammation. On mast cells and basophils, the function of the receptor is well known and constitutes cellular degranulation and the release of various mediators. FcepsilonRI on antigen-presenting cells (APCs), however, does not lead to degranulation of preformed granula, but has different functions: signal transduction pathways like the activation of NF-kappaB are initiated to induce inflammatory cytokine gene expression. In addition, FcepsilonRI on APCs acts as an allergen-focusing structure and can efficiently amplify allergen presentation in an IgE-dependent manner. Recently, we and others have gained new insight into the regulation and function of FcepsilonRI on APCs, which has shed new light on the modulating effects of the immune system in atopic inflammation.

Animals↗

Quantification of indoleamine 2,3-dioxygenase gene induction in atopic and non-atopic monocytes after ligation of the high-affinity receptor for IgE, Fc(epsilon)RI and interferon-gamma stimulation.

Antigen-presenting cells (APCs) are crucial in regulating the outcome of T cell responses. Certain APCs are able to down-regulate T cell proliferation in vitro by inducing the enzyme indoleamine 2,3-dioxygenase (IDO) upon interferon-gamma (IFN-gamma) stimulation. IDO is the rate-limiting enzyme in the catabolism of the essential amino acid tryptophan. A lack of extracellular tryptophan creates environments in which cells become starved for this amino acid. The high-affinity receptor for IgE, Fc(epsilon)RI, is the principal receptor for the binding of specific IgE in type I-mediated allergies. We demonstrated recently that IDO is overexpressed in Fc(epsilon)RI-stimulated monocytes. In the present study, we performed quantification of IDO gene induction after treatment of atopic (Fc(epsilon)RI(high)) and non-atopic (Fc(epsilon)RI(low/-)) monocytes with IgE/anti-IgE and IFN-gamma. By quantitative PCR ELISA, we found IDO molecule induction in atopic monocytes was enhanced about 50-fold over non-atopic monocytes after ligation of Fc(epsilon)RI. Stimulation with IFN-gamma at a concentration of 100 U/ml in culture medium caused an increase in IDO gene copy numbers in atopics of about fourfold over that of non-atopics. This comparative quantification study demonstrates clearly the regulation of IDO gene expression by Fc(epsilon)RI and discloses differences thereof in atopic and non-atopic cells upon inflammatory stimuli.

Antigen-Presenting Cells↗