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Biomedical subjects

T Bieber

Publications and source records attributed to T Bieber.

At least 55 records · Page 3Linked to original sources
PubMed2002

Generation of dendritic cell-based vaccines for cancer therapy.

Dendritic cells play a major role in the generation of immunity against tumour cells. They can be grown under various culture conditions, which influence the phenotypical and functional properties of dendritic cells and thereby the consecutive immune response mainly executed by T cells. Here we discuss various conditions, which are important during generation and administration of dendritic cells to elicit a tumouricidal T cell-based immune response.

Antigen Presentation↗
PubMed2002

Antigen-presenting cells and tolerance induction.

T cell tolerance induction to foreign and self-antigens has occupied research since the beginning of the understanding of the immune system. Much controversy still exists on this question even though new methods became available to investigate immunoregulatory mechanisms. Antigen-presenting cells play a pivotal role in transferring information from the periphery of the organism to lymphoid organs. There, they initiate not only the activation of naive T cells but seem to deliver important signals which result in T cell unresponsiveness with antigen-specific tolerance induction.

Animals↗
PubMed2002

Characterization of monocyte subtypes in the allergic form of atopic eczema/dermatitis syndrome.

BACKGROUND: Monocyte (Mo) subsets exhibiting distinct phenotypic and functional properties identified in peripheral blood are assumed to be under the control of soluble factors from their surrounding micromilieu. Atopic eczema/dermatitis syndrome (AEDS) is accompanied by humoral and cellular alterations among which an increased expression of the high-affinity receptor for IgE (Fc epsilon RI) on antigen presenting cells, like Mo, could be found. Therefore we analyzed the assembly of circulating Mo populations and their Fc epsilon RI surface expression during the course of AEDS. METHODS: Blood samples were taken from AEDS patients before and after topical treatment as well as from psoriasis patients and healthy control donors. Detailed analysis of Mo subsets was done by flow cytometry. Meticulous clinical scoring included quantification of the surface damage using the eczema area and severity index (EASI score) as well as evaluation of the serum level of thymus- and activation-regulated chemokine (TARC); this was done before and after 2 weeks of topical treatment with tacrolimus ointment 0.1%. RESULTS: During the exacerbation phase of AEDS, patients harboured a different assembly of Mo subtypes from normal nonatopic individuals and patients with psoriasis with a significant increased population of CD14(+)CD64(-) CD16(+) Mo. Clinical improvement led to a significant decrease of this subpopulation in favor of CD14(+)CD64(+)CD16(-) Mo, leading to a composition of Mo subsets similar to the state found in healthy donors. Interestingly, Fc epsilon RI expression was confined to the CD14(+)CD64(+)CD16(-) Mo subpopulation and the percentage of this Fc epsilon RI(+) Mo subset increased significantly in the peripheral blood after topical treatment. CONCLUSION: Our data provide for the first time clear evidence that fluctuations of Mo subsets in AEDS might reflect qualitatively and quantitatively distinct contributions of Mo subsets to the development of AEDS.

Adult↗
PubMed2002

The value of lymphocytopenia as a marker of systemic involvement in cutaneous lupus erythematosus.

BACKGROUND: Some patients suffering from cutaneous lupus erythematosus (CLE) develop extracutaneous manifestations during the course of the disease: up to 5% of patients with discoid LE (DLE) and up to 30% of subacute cutaneous LE (SCLE) patients show systemic involvement. Recent studies revealed some markers indicating systemic manifestations of CLE patients. However, the significance of diminished peripheral lymphocyte numbers as a marker of systemic involvement in CLE has not been investigated before. OBJECTIVES: To determine the value of lymphocytopenia (< 1500 cells microL(-1)) as a marker of extracutaneous manifestations in CLE patients. : Methods The records of 72 CLE patients (44 DLE; 28 SCLE) were investigated. Systemic involvement was defined in accordance with the criteria of the European Academy of Dermatology and Venereology. Analyses of peripheral lymphocyte numbers were done by fluorescence-activated cell sorter analysis. RESULTS: Five CLE patients developed extracutaneous manifestations during the course of disease. All these patients were lymphocytopenic. Differences between peripheral lymphocyte numbers of CLE patients with and without additional systemic involvement were highly significant (P < 0.01). CONCLUSIONS: Our results suggest that lymphocytopenia in patients with CLE is a high sensitive but low specific marker of systemic involvement.

Adult↗
PubMed2001

Cationized human serum albumin as a non-viral vector system for gene delivery? Characterization of complex formation with plasmid DNA and transfection efficiency.

Cationized human serum albumin (cHSA) could serve as a potential non-viral vector system for gene delivery. Native human serum albumin was cationized by covalent coupling of hexamethylenediamine to the carboxyl groups resulting in a shift of the isoelectric point from pH 4-5 to 7-9. The cationized albumin underwent spontaneous self-assembly with DNA as demonstrated by retardation of CMV-nlacZ plasmid in agarose gel electrophoresis. Photon correlation spectroscopy showed a decrease of complex size with increasing cHSA/plasmid ratios. Under optimized conditions complexes were formed with 230-260 nm mean diameter and a homogenous, narrow size distribution. At room temperature complexes were stable in 0.9% sodium chloride solution pH 7.4 for 1 h without aggregation. Process parameters such as albumin concentration, incubation time, temperature, pH, order of reagent addition, the presence of bivalent ions and the ionic strength of the complexation medium all influenced the complex size. Confocal laser scanning microscopy showed interactions of a Texas Red labeled cationized albumin with cell membranes of ECV 304 cells and an enhanced endocytic uptake compared to native albumin. The potential for introducing exogeneous DNA into cells was shown using NIH 3T3 fibroblasts. Successful, albeit low reporter gene expression could be achieved in the presence of chloroquine. Under in vitro conditions no toxic effect could be observed. In conclusion, cationized albumin may have promise as a non-toxic vector for gene delivery, especially for DNA vaccination.

DNA↗
PubMed2001

Engagement of Fc epsilon RI on human monocytes induces the production of IL-10 and prevents their differentiation in dendritic cells.

The local cytokine environment and the presence of stimulatory signals determine whether circulating monocytes will finally acquire characteristics of dendritic cells (DCs) or macrophages. Because FcepsilonRI expressed on professional APCs, e.g., monocytes and DCs, has been suggested to play a key role in the pathophysiology of atopic diseases, we evaluated the effect of receptor ligation on the generation of monocyte-derived DCs (MoDCs). Aggregation of FcepsilonRI at the initiation of the IL-4-GM-CSF-driven differentiation resulted in the emergence of macrophage-like cells with a strong expression of the mannose receptor and a low level of CD1a and the DC-specific markers CD83 and the actin-bundling protein (p55). These cells sustained the ability to take up FITC-labeled Escherichia coli by phagocytosis and were significantly less efficient in stimulating purified allogeneic T cells. In addition, receptor ligation of FcepsilonRI at the beginning of the culture prevented the generation of MoDCs, mainly due to a dramatic increase in the IL-10 production. These results suggest that FcepsilonRI aggregation prevents the generation of CD1a(+) MoDCs and imply a novel pivotal function of this receptor in modulating the differentiation of monocytes.

Cell Differentiation↗
PubMed2001

Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial.

Therapeutic vaccination of tumor patients with cytokine gene-transfected tumor cells leads to tumor regression in animal models but has so far not resulted in significant clinical benefit. We and others demonstrated that tumor cells transfected to mediate overexpression of a cytokine gene activate immunologic effector cells for an improved proliferation rate and significantly higher antitumoral cytotoxic activity. Here, we performed a pilot study of therapeutic vaccination in patients with metastatic disease. Autologous tumor cells were simultaneously transfected with novel minimalistic, immunogenically defined, gene expression constructs (MIDGE) for overexpression of the two cytokines interleukin 7 (IL-7) and GM-CSF and newly designed double stem-loop immunomodulating oligodeoxyribonucleotides (d-SLIM) as a Th1-promoting and NK cell-stimulating adjuvant. Transfection was performed ex vivo by ballistomagnetic gene transfer. Patients received four subcutaneous injections of at least 1 x 10(6) of their expression-modulated and immunomodified autologous tumor cells. Ten patients have been enrolled in the study protocol. In all patients no adverse effects could be detected. IL-7 and interferon gamma levels were elevated in the serum of the patients after treatment. Interestingly, cytotoxicity of patient-derived PBLs increased significantly during treatment. All 10 patients had progressive disease when entering our protocol. One complete, one partial, and one mixed response with progression of abdominal metastases and regression of lung metastases were observed. Two patients showed a stable disease after treatment and five patients remained in progressive disease. Our observations confirm the capability of autologous expression-modified and immunomodulated tumor cell vaccines to stimulate a strong immune response in patients with metastatic cancer even in the presence of a large tumor burden.

Aged↗
PubMed2001

Association of inclusion body myositis with subacute cutaneous lupus erythematosus.

We present the case of a 71-year-old man with inclusion body myositis combined with subacute cutaneous lupus erythematosus and dysphagia. Although inclusion body myositis is usually resistant to immunosuppressive therapy, this patient improved under treatment with corticosteroids. The presented case is discussed in the context of earlier reports of inclusion body myositis and lupus erythematosus.

Aged↗
PubMed2001

In situ expression of the costimulatory molecules CD80 and CD86 on langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis.

The functional expression of costimulatory molecules on antigen-presenting cells may be a key event in the pathogenesis of atopic dermatitis (AD). Recently, the expression of CD86 (B7-2/B70) has been demonstrated on CD1a+ epidermal dendritic cells (DC) in AD lesions by immunohistological and functional analysis. Therefore, we sought to further characterize the in situ expression of costimulatory molecules on these cells, considering the two subpopulations of (1) CD1a+++/CD11b- Langerhans cells (LC) containing Birbeck granules and (2) CD1a+/CD11b+++ inflammatory dendritic epidermal cells (IDEC), devoid of Birbeck granules, from AD and other inflammatory skin diseases. Flow cytometry, skin mixed lymphocyte reactions (SMLR) and immunohistological analysis were performed, and showed that IDEC and not LC are the relevant cells expressing the costimulatory molecules CD80 and CD86 in situ. This expression varied with the underlying diagnosis, with AD showing the highest expression of both CD80 and CD86 in situ. Furthermore, the expression of CD80, CD86 and CD36 were significantly correlated. With short-term culture, both CD80 and CD86 were further upregulated on LC and IDEC. Finally, anti-CD86 antibody reduced the stimulatory activity of epidermal DC. These results indicate that costimulatory molecules on LC and IDEC might play a role in the pathogenesis of AD.

Antigens, CD↗
PubMed2001

IgE receptors.

IgE receptors are implicated as important components of the immunological pathway in allergic and inflammatory diseases. Recent investigations have begun to unravel the structure, signal transduction and function of IgE receptors from different cell types in rodent and human systems. Studies of the mechanisms involved might provide opportunities for therapeutic intervention strategies in the treatment of allergic and hypersensitivity reactions.

Animals↗
PubMed2001

Sporotrichoid phaeohyphomycosis due to Alternaria infectoria.

We describe a cardiac transplant patient who had human cutaneous alternariosis with a sporotrichoid distribution of skin lesions. In this patient identification of the causative organism Alternaria infectoria was achieved by sequencing the rDNA internal transcribed spacer domain. Treatment with itraconazole led to clinical resolution within 4 months.

Alternaria↗