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Biomedical subjects

Dieter Meier

Publications and source records attributed to Dieter Meier.

6 recordsLinked to original sources

Natural brominated phenoxyphenols kill persistent and biofilm-incorporated cells of MRSA and other pathogenic bacteria.

Due to a high unresponsiveness to chemotherapy, biofilm formation is an important medical problem that frequently occurs during infection with many bacterial pathogens. In this study, the marine sponge-derived natural compounds 4,6-dibromo-2-(2',4'-dibromophenoxy)phenol and 3,4,6-tribromo-2-(2',4'-dibromophenoxy)phenol were found to exhibit broad antibacterial activity against medically relevant gram-positive and gram-negative pathogens. The compounds were not only bactericidal against both replicating and stationary phase-persistent planktonic cells of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa; they also killed biofilm-incorporated cells of both species while not affecting biofilm structural integrity. Moreover, these compounds were active against carbapenemase-producing Enterobacter sp. This simultaneous activity of compounds against different growth forms of both gram-positive and gram-negative bacteria is rare. Genome sequencing of spontaneous resistant mutants and proteome analysis suggest that resistance is mediated by downregulation of the bacterial EIIBC phosphotransferase components scrA and mtlA in MRSA likely leading to a lower uptake of the molecules. Due to their only moderate cytotoxicity against human cell lines, phenoxyphenols provide an interesting new scaffold for development of antimicrobial agents with activity against planktonic cells, persisters and biofilm-incoporated cells of ESKAPE pathogens. KEY POINTS: • Brominated phenoxyphenols kill actively replicating and biofilm-incorporated bacteria. • Phosphotransferase systems mediate uptake of brominated phenoxyphenols. • Downregulation of phosphotransferase systems mediate resistance.

Animals↗

Cerebral metabolic alterations in McLeod syndrome.

The X-linked McLeod neuroacanthocytosis syndrome is a multisystem disorder with central nervous system manifestations resembling Huntington's disease. We examined 5 McLeod patients and 5 asymptomatic heterozygous females with fast multiple spin-echo spectroscopic imaging. Three patients with pronounced psychiatric or cognitive manifestations had pathological N-acetyl aspartate/(creatine + choline) ratios in frontal, temporal, and insular areas, with an individual pattern. Two patients with a severe choreatic movement disorder had unilateral thalamic alterations. One patient with moderate movement disorder and personality disorder had bilateral occipital alterations. One female heterozygote had unilateral insular metabolic alterations, possibly indicating subclinical cerebral involvement. Although the prominent psychiatric and cognitive manifestations in McLeod patients suggest significant and widespread cortical abnormalities, previous neuroradiological and histopathological data had not revealed definite extrastriatal pathology. Our findings demonstrating metabolic abnormalities in different brain regions of McLeod patients might either reflect neuronal dysfunction due to impaired basal ganglia-thalamo-cortical circuits or subtle structural alterations in the particular cerebral areas.

Adult↗

Improved two-dimensional J-resolved spectroscopy.

Localised two-dimensional J-resolved spectroscopy (JPRESS) is optimised for the in vivo detection of J-coupled metabolites using magnetic resonance spectroscopy at 3 T. The acquisition of echo signals starts as early as possible (i.e. maximum-echo sampling). This sampling scheme increases sensitivity and decreases overlap of peak tails, hence alleviating baseline problems. Reconstruction issues are discussed and the sensitivity is compared analytically with that of 1D PRESS. The qualitative behaviour of eddy currents in JPRESS is outlined and a 2D eddy current correction procedure based on the 1D phase deconvolution method is proposed.

Adult↗

Optimizing PRESS localized citrate detection at 3 Tesla.

Analytical methods are used to characterize the response of the strongly coupled two-spin system of citrate to point-resolved spectroscopy (PRESS)-based sequences at 3 T. The signal output is analyzed line by line, as well as in the Cartesian product operator basis. Patterns with a periodicity of 80.9 ms are identified. Furthermore, it is shown that at TE = n . 80.9 ms (n in {0,1,2,...}), the spin evolution can be described without direct reference to strong coupling terms. The theoretical results are found to be in good agreement with in vivo experiments. These results can be used to design protocols for prostate MRS and MRSI at 3 T, and give guidelines for optimizing spin-echo-based acquisition schemes for detecting two-spin systems at arbitrary field strengths.

Adult↗

Parallel spectroscopic imaging with spin-echo trains.

A reduction in scan time in spectroscopic imaging (SI) can be achieved by both fast and reduced k-space sampling. This work presents an ultrafast SI technique that combines the two approaches. The synergy of multiple spin-echo (MSE) acquisition and sensitivity encoding (SENSE) enables high-resolution SI to be performed within a clinically acceptable scan time. MSE-SENSE-SI with echo train lengths ranging from one to four echoes is evaluated with respect to SNR and spatial response function by means of in vitro experiments. It is shown that acquiring two spin-echoes (SEs) per acquisition yields a good practical trade-off among scan time, SNR, and spatial response. The clinical feasibility of the technique is demonstrated in a patient with an astrocytoma, and SI data are obtained with an image matrix of 24 x 24 in just over 2 min.

Astrocytoma↗

In vivo 1H NMR spectroscopy of individual human brain metabolites at moderate field strengths.

This article reviews spectral editing techniques for in vivo 1H NMR spectroscopy of human brain tissue at moderate field strengths of 1.5-3 Tesla. Various aspects of 1H NMR spectroscopy are discussed with regard to in vivo applications. The parameter set [delta, J, n] (delta being the relative chemical shift, J the scalar coupling constant and n the number of coupled spins) is used to characterize the spin systems under investigation and to classify the editing techniques that are used in in vivo 1H NMR spectroscopy.

Brain↗