Biomedical subjects
Publications and source records attributed to C Meier.
Novel cyclic and acyclic analogues of dTMP and AZTMP were synthesized from the corresponding cycloSal-phosphotriesters. This method yielded the nucleotides in good yields with a simple work-up. Investigation of the substrate properties of the modified nucleotides towards TmpK showed, that they are very poor substrates for this key enzyme in the bioactivation of AZT.
Benzyl-substituted cycloSal-d4T monophosphates were prepared and evaluated for their ability to release d4TMP selectively. In contrast to previously reported derivatives, two of the new compounds release d4TMP as the sole product while two others gave the expected benzyl phosphate diesters. However, these diesters were surprisingly stable against degradation to release d4TMP.
An acetylcholinesterase (AChE) assay based on the Rappaport method was established to investigate the behaviour of several cycloSal nucleotides against AChE from electrophorus electricus and human sources (purified enzymes). AChE is a physiologically essential enzyme as it catalyzes the hydrolysis of the neurotransmitter acetylcholine. No inhibition was observed in any of the cases.
A new route towards an enantiomerically pure carbocyclic 2'-deoxyribonucleoside precursor was developed. After coupling with a nucleobase the product is easily accessible for further modifications at the 3'-hydroxy group.
C8-Arylamine-dG adducts were synthesized by palladium-catalyzed cross-coupling reactions. The corresponding 5'-O-DMTr-3'-O-phosphoramidite-C8-arylamine-dG adducts were synthesized as potential building blocks for the automated synthesis of site-specifically modified oligonucleotides.
Phthalidyl modified oligonucleotide thymidine-thymidine dimer building blocks were synthesized via the H-phosphonate-method. The compounds which are diastereomeric at the phosphorus atom were separated by chromatography and the absolute configuration at the phosphorus atoms was determined using ROE-experiments using the corresponding methyl-phosphonates.
Glial bundles growing out of the spinal cord were observed in spinal nerve roots in the pig after their section and surgical repair. The heterotopic occurrence of glial cells, most of which were identified as astrocytes, was more frequent and more pronounced in dorsal than in ventral roots. Several of the glial bundles contained regenerated myelinated axons. These were probably myelinated by cells which showed the typical cytological criteria for oligodendrocytes and the mode of myelination was clearly of central type. It was concluded that the glial outgrowth is induced by degeneration and regeneration of axons passing the central-peripheral transition zone.
We evaluated a new liquid homogeneous assay for the direct measurement of high density lipoprotein cholesterol (HDL-C Plus) in seven laboratories. The assay includes two reagents which can be readily used in most available clinical chemistry analyzers. The total CVs of the new method were below 4.6% and the bias in relation to the designated comparison method was below 3.9%. The total error ranged between 4 to 7%. HDL-C values determined by this method were in good agreement with those obtained by the old homogeneous assay using lyophilized reagents, and other homogeneous and precipitation assays (0.944 < r < 0.996). The assay was linear up to at least 3.89 mmol/l HDL-C. Hemoglobin did not interfere, whereas in icteric samples slight deviations were observed. Lipemia up to 11.3 to 22.6 mmol/l triglycerides did not interfere with this homogeneous HDL-C assay. In samples of patients with paraproteinemia, discrepant results were seen. This liquid homogeneous HDL-C assay was easy to handle and produced similar results in all laboratories participating in this study. This method will enable clinical laboratories to reliably measure HDL-C for risk assessment of coronary heart disease.
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The density of mast cells (MC) in human sural nerve biopsies of different neuropathies (NP) was determined by counting cells expressing naphtol-AS-D-chloracetate-esterase-activity. Morphometry of the different nerve compartments was performed and the counts for the endoneurial (including the perineurial) compartment were compared to the counts for the epineurial compartment. In most cases the density of the MC was notably higher in the epineurial than in the endoneurial compartment. The density of MC appeared to be correlated especially with demyelinating diseases.