Biomedical subjects

Andreas Keller

Publications and source records attributed to Andreas Keller.

5 recordsLinked to original sources

PubMed2025

Comparative in vitro activity of ceftazidime-avibactam plus aztreonam and the fixed combination aztreonam/avibactam against multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVES: MDR Pseudomonas aeruginosa is difficult to treat, despite some new beta-lactam/beta-lactamase inhibitors. A combination of ceftazidime-avibactam and aztreonam (CAZ/AVI + AZT) is frequently used to treat Gram-negative bacteria expressing metallo-beta-lactamases. A fixed combination of aztreonam/avibactam was recently licenced for use in Europe, but it remains unknown whether there are differences between both options for use against P. aeruginosa. This study evaluates the comparative in vitro efficacy of the fixed combination aztreonam/avibactam compared to the three antibiotics CAZ/AVI + AZT against clinical MDR P. aeruginosa isolates. METHODS: MICs for aztreonam/avibactam and CAZ/AVI + AZT were determined in 38 MDR P. aeruginosa isolates recovered from routine diagnostics using broth microdilution with checkerboard assays in triplicates as the reference method. Fractional inhibitory concentration (FIC) indices were calculated. Whole-genome sequencing was performed on all isolates. RESULTS: At a fixed ceftazidime concentration of 8 mg/L (EUCAST breakpoint), 25 isolates exhibited lower MICs for CAZ/AVI + AZT compared to aztreonam/avibactam alone in microdilution assays. On FIC analysis, additive and synergistic effects were seen in 28 and 2 cases, respectively. Verona integron-encoded metallo-beta-lactamase (VIM) was the most prevalent carbapenemase (21/38 isolates), followed by Imipenemase (IMP, 4/38) and New Delhi metallo-beta-lactamase (NDM, 2/38). Lower MICs were observed for the combination CAZ/AVI + AZT in isolates carrying VIM-2 as compared to VIM-1. CONCLUSIONS: In vitro testing of CAZ/AVI + AZT revealed increased in vitro susceptibility among MDR P. aeruginosa isolates in comparison to the fixed combination of aztreonam/avibactam.

Pseudomonas aeruginosa↗

PubMed2003

Decoding olfaction in Drosophila.

Recent experiments in Drosophila demonstrate striking stereotypy in the neural architecture of the olfactory system. Functional imaging experiments in mammals and honeybees suggest a mechanism of odor coding that translates discrete patterns of activity in olfactory glomeruli into an odor image. Future experiments in Drosophila may permit a direct test of this odor-coding hypothesis.

Animals↗

PubMed2003

[Improvement of the accuracy of the Laplace transform method for the determination of radiotherapy spectra of clinical linear accelerators].

The present study focused on the reconstruction of the bremsstrahlung spectrum of a clinical linear accelerator from the measured transmission curve, with the aim of improving the accuracy of this method. The essence of the method was the analytic inverse Laplace transform of a parameter function fitted to the measured transmission curve. We tested known fitting functions, however they resulted in considerable fitting inaccuracy, leading to inaccuracies of the bremsstrahlung spectrum. In order to minimise the fitting errors, we employed a linear combination of n equations with 2n-1 parameters. The fitting errors are now considerably smaller. The measurement of the transmission function requires that the energy-dependent detector response is taken into account. We analysed the underlying physical context and developed a function that corrects for the energy-dependent detector response. The factors of this function were experimentally determined or calculated from tabulated values.

Models, Theoretical↗

PubMed2002

Targeted expression of tetanus neurotoxin interferes with behavioral responses to sensory input in Drosophila.

Targeted inactivation of neurons by expression of toxic gene products is a useful tool to assign behavioral functions to specific neurons or brain structures. Of a variety of toxic gene products tested, tetanus neurotoxin light chain (TNT) has the least severe side effects and can completely block chemical synapses. By using the GAL4 system to drive TNT expression in a subset of chemo- and mechanosensory neurons, we detected walking and flight defects consistent with blocking of relevant sensory information. We also found, for the first time, an olfactory behavioral phenotype associated with blocking of a specific subset of antennal chemoreceptors. Similar behavioral experiments with GAL4 lines expressing in different subsets of antennal chemoreceptors should contribute to an understanding of olfactory coding in Drosophila. To increase the utility of the GAL4 system for such purposes, we have designed an inducible system that allows us to circumvent lethality caused by TNT expression during early development.

Alleles↗

PubMed2002

Targeted expression of tetanus toxin: a new tool to study the neurobiology of behavior.

Over the past few decades, the explosion of molecular genetic knowledge, particularly in the fruit fly Drosophila melanogaster, has led to the identification of a large number of genes, which, when mutated, directly or indirectly affect fly behavior. Beyond the genetic and molecular characterization of genes and their associated molecular pathways, recent advances in molecular genetics also have allowed the development of new tools dedicated more directly to the dissection of the neural bases for various behaviors. In particular, the conjunction of the development of two techniques--the enhancer-trap detection system and the targeted gene expression system, based on the yeast GAL4 transcription factor--has led to the development of the binary enhancer-trap P[GAL4] expression system, which allows the selective activation of any cloned gene in a wide variety of tissue- and cell-specific patterns. Thus, this development, in addition to allowing the anatomical characterization of neuronal circuitry, also allows, via the expression of tetanus toxin light chain (known to specifically block synaptic transmission), an investigation of the role of specific neurons in certain behaviors. Using this system of "toxigenetics," several forms of behavior--from those mediated by sensory systems, such as olfaction, mechanoreception, and vision, to those mediated by higher brain function, such as learning, memory and locomotion--have been studied. These studies aim to map neuronal circuitry underlying specific behaviors and thereby unravel relevant neurophysiological mechanisms. The advantage of this approach is that it is noninvasive and permits the investigation of behavior in the free moving animal. We review a number of behavioral studies that have successfully employed this toxigenetic approach, and we hope to persuade the reader that transgenic tetanus toxin light chain is a useful and appropriate tool for the armory of neuroethologists.

Animals↗