Browsing by Author "Schulz, Sarah"

Background. Sensitization to aeroallergens is a frequent event in patients with atopic dermatitis (AD). The role of allergen-specific T cells in the pathogenesis of AD is, however, not fully clear. A detailed immunological characterization of allergen-specific T cells able to migrate to inflamed skin might therefore be helpful in determining the relevance of allergen-specific T cells to clinical symptoms. Objective: To establish a simple assay to simultaneously monitor the expression of skin-related homing molecules and their proliferative response to an allergen on peripheral T cells. To evaluate whether this assay is able to identify AD patients in whom exposure to an allergen induces dermatitis. Methods: The expression of CLA, CD7 and CD4 was simultaneously measured by flow cytometry with the DNA content as a parameter of proliferation at the single cell level. House dust mite antigen (DerP) and tetanus toxoid (TT) were used as antigens. Results: CD4+ CLA+ CD7-, but not CLA- T cells from patients with AD proliferated and expanded following DerP stimulation. In contrast, TT stimulation resulted in proliferation of both, CLA+ and CLA- T cells from both, atopic and healthy donors. Conclusions: Single cell analysis revealed a predominant localization of allergen-reactive T cells within the CD7- CLA+ CD4+ T cell subset in AD. Thus, this simple assay not only confirms previously published results, but also extends our knowledge on the biology of CLA and CD7 cells in AD. Ultimately, this will be helpful in classifying those patients who might benefit from allergen avoidance therapies. Copyright (C) 2003 S. Karger AG, Basel.

Two new caprolactones, (R)-10-methyl-6-undecanolide (1) and (6R,10S)-10-methyl-6-dodecanolide (2), were identified in the lipid extract of a marine streptomycete (isolate B6007). Their structures were proposed on the basis of GC-MS experiments and proved by synthesis. The absolute configuration of the compounds was established by comparison of the natural and synthetic stereoisomers using chiral gas chromatography. These caprolactones show a moderate phytotoxicity and a promising activity against cancer cells with concomitant low general cytotoxicity.

The combination of holoprosencephaly, postaxial polydactyly, and normal karyotype has been termed pseudotrisomy 13 syndrome. Here, we report the prenatal diagnosis of pseudotrisomy 13 in three siblings suggesting autosomal recessive inheritance of this syndrome. Clinical overlap with hydrolethalus syndrome, Smith-Lemli-Opitz syndrome, Meckel syndrome, and Pallister-Hall syndrome is discussed. Copyright (c) 2005 S. Karger AG, Basel.

Isopeptidases are essential regulators of protein ubiquitination and sumoylation. However, only two families of SUMO isopeptidases are at present known. Here, we report an activity-based search with the suicide inhibitor haemagglutinin (HA)-SUMO-vinylmethylester that led to the identification of a surprising new SUMO protease, ubiquitin-specific protease-like 1 (USPL1). Indeed, USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells. C13orf22l-an essential but distant zebrafish homologue of USPL1-also acts on SUMO, indicating functional conservation. We have identified invariant USPL1 residues required for SUMO binding and cleavage. USPL1 is a low-abundance protein that colocalizes with coilin in Cajal bodies. Its depletion does not affect global sumoylation, but causes striking coilin mislocalization and impairs cell proliferation, functions that are not dependent on USPL1 catalytic activity. Thus, USPL1 represents a third type of SUMO protease, with essential functions in Cajal body biology.