ABSTRACT
Using non-invasive, marker-free resonance enhanced dynamic light scattering, the dynamics of capillary waves on ultrathin polystyrene films' coupling to the viscoelastic and mechanical properties have been studied. The dynamics of ultrathin polymer films is still debated. In particular the question of what influence either the solid substrate and/or the fluid-gas interface has on the dynamics and the mechanical properties of films of glass forming liquids as polymers is in the focus of the present research. As a consequence, e.g., viscosity close to interfaces and thus the average viscosity of very thin films are prone to change. This study is focused on atactic, non-entangled polystyrene thin films on the gold surface. A slow dynamic mode was observed with Vogel-Fulcher-Tammann temperature dependence, slowing down with decreasing film thickness. We tentatively attribute this relaxation mode to overdamped capillary waves because of its temperature dependence and the dispersion with a wave vector which was found. No signs of a more mobile layer at the air/polymer interface or of a "dead layer" at the solid/polymer interface were found. Therefore we investigated the influence of an artificially created dead layer on the capillary wave dynamics by introducing covalently bound polystyrene polymer brushes as anchors. The dynamics was slowed down to a degree more than expected from theoretical work on the increase of density close to the solid liquid interface-instead of a "dead layer" of 2 nm, the interaction seems to extend more than 10 nm into the polymer.
ABSTRACT
Human sera are the first choice as controls for diagnostic applications such as immunoassays, but are limited regarding availability, varying quality, and high costs. In this study, we aimed to circumvent these limitations by the use of a chimeric adaptor molecule comprising the extracellular domains of the human FcγRI (CD64) fused with human IgE Fc domains (CD64-IgE Fc). Allergen-specific antibodies were produced in rabbits using eight different allergens, extracts, and allergen mixtures including mites, pollen, drugs, and food. Preincubation of polyclonal IgG with CD64-IgE Fc established allergen-specific artificial sera that showed comparable results for more than 20 allergens and allergen extracts in three diagnostic systems for the determination of specific IgE. The agreement for these artificial sera is within ±1 radioallergosorbent test (RAST) class. Hence, rabbit IgG complexed with the IgG-specific CD64-IgE Fc adaptor molecule could provide a substitute for human reference sera with specificity for virtually any protein of interest.
Subject(s)
Allergens/immunology , Antibodies/immunology , Blood Substitutes/adverse effects , Immunoglobulin E/immunology , Receptors, IgG/immunology , Recombinant Fusion Proteins/immunology , Antibodies/genetics , Antibody Specificity/immunology , Cell Line , Enzyme-Linked Immunosorbent Assay , Gene Expression , Humans , Immunization , Immunoglobulin E/chemistry , Immunoglobulin E/genetics , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Protein Binding/immunology , Protein Domains/genetics , Protein Domains/immunology , Receptors, IgG/chemistry , Receptors, IgG/genetics , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/isolation & purification , Recombinant Fusion Proteins/metabolismABSTRACT
In Germany, too, adverse drug events (ADEs) have been identified as a central problem in the care of geriatric patients. Especially in elderly patients with multimorbidity and increasing frailty, ADEs are among the most frequent and cost-intensive causes of illness in healthcare. In most cases, they are due to drug-related diseases, which necessitate enhanced risk awareness and improved cooperation between physicians, medical specialists, geriatric nurses and pharmacists. In this context, the use of urologic medication for geriatric patients requires particular attention by the consultant.
Subject(s)
Interdisciplinary Communication , Intersectoral Collaboration , Pharmaceutical Services , Urologic Diseases/drug therapy , Urological Agents/adverse effects , Urological Agents/therapeutic use , Aged , Comorbidity , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Female , Humans , Male , Risk FactorsABSTRACT
BACKGROUND: Analyses of the molecular basis underlying allergenicity and allergen cross-reactivity, as well as improvement of allergy diagnostics and therapeutics, are hampered by the lack of human monoclonal IgE antibodies and knowledge about their epitopes. Here, we addressed the consecutive generation and epitope delineation of a human monoclonal IgE against the prototypic allergen Bet v 1. METHODS: Phage-display scFv hybrid libraries of allergic donor-derived VH epsilon and synthetic VL were established from 107 mononuclear cells. An obtained scFv was converted into human immunoglobulin formats including IgE. Using variants of Bet v 1, the epitope of the antibody was mapped and extrapolated to other PR10 proteins. RESULTS: The obtained antibodies exhibited pronounced reactivity with Bet v 1, but were not reactive with the homologous PR10 protein Mal d 1. The epitope as defined by the IgE paratope and a set of chimeric Bet v 1 fusion proteins and fragments could be assigned to a C-terminal helix-structured motif comprised by amino acid residues 132-154, including the critical residue E149. Grafting this motif re-established the reactivity of the per se nonreactive Mal d 1 framework. Cross-reactivities predicted by primary structure analyses of different isoforms and PR10 proteins were verified by allergen chip-based analyses. CONCLUSIONS: The obtained results demonstrate that hybrid IgE repertoires represent a source for human antibodies with genuine paratopes. The IgE-derived information about the IgE epitope nature of Bet v 1 and homologues allows for detailed insights into molecular aspects of allergenicity and cross-reactivity within the PR10 protein family.
Subject(s)
Allergens/immunology , Antigens, Plant/immunology , Epitopes/immunology , Fagus/immunology , Immunoglobulin E/immunology , Plant Proteins/immunology , Allergens/chemistry , Amino Acid Sequence , Antibody Specificity , Antigens, Plant/chemistry , Cross Reactions/immunology , Epitopes/chemistry , Gene Library , Humans , Immunoglobulin E/chemistry , Immunoglobulin E/genetics , Immunoglobulin Heavy Chains/chemistry , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Variable Region/chemistry , Immunoglobulin Variable Region/genetics , Models, Molecular , Molecular Sequence Data , Peptide Library , Plant Proteins/chemistry , Protein Conformation , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Sequence AlignmentABSTRACT
We report on an experiment in which a negative hydrogen ion beam in the Spallation Neutron Source (SNS) linear accelerator was replaced with a beam of protons with similar size and dynamics. Fractional beam loss in the superconducting part of the SNS accelerator was measured to be at least 2×10(-5) for the H(-) beam, and it was an order of magnitude lower for the protons. Also beam loss has a stronger dependence on intensity with H(-) than with proton beams. These measurements verify a recent theoretical explanation of unexpected beam losses in the SNS superconducting linear accelerator based on an intrabeam stripping mechanism for negative hydrogen ions. This previously unidentified mechanism for beam loss is important for the design of new high current linear ion accelerators and the performance improvement of existing machines.
ABSTRACT
Signaling of TGF-beta superfamily members is tightly controlled by an elaborate network of regulators (for recent review see Trends Genet. 15 (1999) 3; Genes Dev. 14 (2000) 627). Recently, the transmembrane protein BAMBI (BMP and activin membrane-bound inhibitor) has been shown to interfere with Bmp and activin-like signaling by inhibiting Tgf-beta type I receptor activation (Nature 401 (1999) 480). In striking contrast to other Bmp antagonists like noggin (Cell 86 (1996) 599) or chordin (Cell 86 (1996) 589), BAMBI is strictly coexpressed with Bmp-4 during early Xenopus embryogenesis. The grouping of genes according to their shared complex spatial expression pattern and their involvement in the same biological signaling pathway has been referred to as synexpression group. This concept facilitates prognoses about the roles of a group member with unknown function. Apparently, only a minority of genes is organized in synexpression groups and up to now they have mainly been described in yeast and Xenopus (for review see Nature 402 (1999) 483). In the frog, BAMBI is a member of the Bmp-4 synexpression group (Nature 401 (1999) 480). We identified two murine homologues of BAMBI one of which, named Bambi-psi, is a pseudogene. We show that the spatiotemporal expression pattern of Bambi closely matches that of Bmp-4 during mouse embryonic development. Moreover, we show that Bambi expression is induced in mouse embryonic fibroblasts by Bmp-4. Hence, we provide first evidence for the existence of an evolutionarily conserved Bmp-4 synexpression group in mammals.
Subject(s)
Bone Morphogenetic Proteins/biosynthesis , Embryo, Mammalian/metabolism , Gene Expression , Membrane Proteins/biosynthesis , Membrane Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , Bone Morphogenetic Protein 4 , Expressed Sequence Tags , Extremities/embryology , Humans , Mice , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic Acid , Signal Transduction , Time Factors , Tissue Distribution , Xenopus ProteinsABSTRACT
Patients with coronary artery disease have an increased risk of developing intra-operative myocardial ischaemia and peri-operative myocardial infarction. Pre-operative identification of patients at risk of developing peri-operative myocardial ischaemia is often difficult or even impossible due to the inability of the patient to perform an exercise test. For those unable to perform physical exercise a system has recently been described combining transoesophageal echocardiography with simultaneous transoesophageal atrial pacing via the same probe to detect pacing-induced wall motion abnormalities, a sign of coronary artery disease. In a prospective study, 20 patients with clinically suspected coronary artery disease undergoing hip replacement were examined pre-operatively by transoesophageal stress echocardiography. During the subsequent operation the incidence of intra-operative ischaemia was evaluated again in all 20 patients by transoesophageal echocardiography. In eight of the 20 patients (40%) wall motion abnormalities could be induced by transoesophageal stress echocardiography pre-operatively. Intra-operative wall motion abnormalities occurred in six of these eight patients. In two patients with wall motion abnormalities induced by transoesophageal stress echocardiography no abnormalities occurred during surgery. However, in those in whom wall motion abnormalities did occur during operation they occurred in the same left ventricular segment as those initiated by stress echocardiography. None of the patients without pre-operatively inducible wall motion abnormality developed them during surgery. No patient developed a myocardial infarction intra- or post-operatively. Thus, preoperative transoesophageal stress echocardiography is a valuable technique for the detection of patients who may develop ischaemic wall motion abnormalities during surgery.(ABSTRACT TRUNCATED AT 250 WORDS)