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Biomedical subjects

A G Jones

Publications and source records attributed to A G Jones.

117 records · Page 7Linked to original sources
PubMedDate not supplied

Progestin-rhenium complexes: metal-labeled steroids with high receptor binding affinity, potential receptor-directed agents for diagnostic imaging or therapy.

In order to investigate the possibility of developing diagnostic imaging agents for steroid-positive tumors that are labeled with the readily available radionuclide technetium-99m, we prepared four conjugate systems in which a progestin is linked to a metal chelate system. Three of these are bis-amino bis-thiol (BAT or N2S2) systems and are linked through carbon-21 of progesterone or the 17 alpha- or 11 beta-position of a nortestosterone type progestin. The fourth, an amino-amido-thiol-alcohol chelate (N2OS) system, is linked at the 16 alpha,17 alpha-positions of a dihydroprogesterone. As a model for technetium-labeled complexes, all four chelate systems were converted to their oxo-rhenium complexes. Of the four possible diastereomers in the 16 alpha,17 alpha-system, only one was isolated, while of the four possible diastereomers in the other systems, a syn pair and an anti pair (linker methylene vs rhenium-oxo, relative to the N2S2 plane) were separated in the 17 alpha-substituted series, a syn pair was isolated in the 21-substituted series, and a syn pair and the two individual anti diastereomers were separated in the 11 beta-substituted series. In competitive radiometric receptor binding assays, the 21-, 17 alpha-, and 16 alpha,17 alpha-linked systems had low affinity for the progesterone receptor (less than 0.3% that of promegestone (R5020) or 2% that of progesterone). By contrast, the two anti diastereomers of the 11 beta-linked system had affinities that were 10% and 44% that of R5020 (or 64% and 283% that of progesterone) and the syn pair had an affinity 25% that of R5020 (or 161% that of progesterone). The latter finding indicates that it is possible to prepare metal-labeled steroids that retain high affinity for steroid receptors. These and related systems, when complexed with radioactive metals, may be useful in vivo as receptor-directed agents for diagnostic imaging or therapy of steroid receptor-positive tumors.

20-alpha-Dihydroprogesterone↗
PubMedDate not supplied

The [(99m)Tc(N)(PNP)](2+) metal fragment: a technetium-nitrido synthon for use with biologically active molecules. The N-(2-methoxyphenyl)piperazyl-cysteine analogues as examples.

The incorporation of a bioactive molecule into a nitrido-containing (99m)Tc-complex has been successfully achieved by using the [TcN(PNP)](2+) metal fragment. In this strategy, the strong electrophilic [TcN(PNP)](2+) metal fragment efficiently reacts with bifunctional chelating ligands having a pi-donor atom set, such as N-functionalized O,S-cysteine. The 2-methoxyphenylpiperazine (2-MPP) pharmacophore, which displays preferential affinity for 5HT(1A) receptors, was conjugated to the amino group of cysteine to obtain 2-MPPP-cys-OS, where 2-MPPP is 3-[4-(2-methoxyphenyl)piperazin-1-yl]propionate. The asymmetric Tc(V)-nitrido complexes, [(99g/99m)Tc(N)(PNP)(2-MPPP-cys-OS)] (PNP = PNP3, PNP4), were obtained in high yield (95%), by simultaneous addition of PNP and 2-MPPP-cys-OS ligand to a solution containing a starting (99g)/(99m)Tc-nitrido precursor. A mixture of syn and anti isomers was observed, the latter being the thermodynamically favored species. In vitro challenge experiments using the anti isomers with glutathione and cysteine indicated that no transchelation reaction occurs. Assessment of the in vitro 5HT(1A) receptor-affinity of the technetium complexes revealed that only the anti-PNP4 complex possesses some affinity for the receptor, but displayed negligible brain uptake in biodistribution studies in rats in vivo.

Animals↗
PubMedDate not supplied

Mating systems and sexual selection in male-pregnant pipefishes and seahorses: insights from microsatellite-based studies of maternity.

In pipefishes and seahorses (family Syngnathidae), the males provide all postzygotic care of offspring by brooding embryos on their ventral surfaces. In some species, this phenomenon of male "pregnancy" results in a reversal of the usual direction of sexual selection, such that females compete more than males for access to mates, and secondary sexual characteristics evolve in females. Thus the syngnathids can provide critical tests of theories related to the evolution of sex differences and sexual selection. Microsatellite-based studies of the genetic mating systems of several species of pipefishes and seahorses have provided insights into important aspects of the natural history and evolution of these fishes. First, males of species with completely enclosed pouches have complete confidence of paternity, as might be predicted from parental investment theory for species in which males invest so heavily in offspring. Second, a wide range of genetic mating systems have been documented in nature, including genetic monogamy in a seahorse, polygynandry in two species of pipefish, and polyandry in a third pipefish species. The genetic mating systems appear to be causally related to the intensity of sexual selection, with secondary sex characters evolving most often in females of the more polyandrous species. Third, genetic studies of captive-breeding pipefish suggest that the sexual selection gradient (or Bateman gradient) may be a substantially better method for characterizing the mating system than previously available techniques. Finally, these genetic studies of syngnathid mating systems have led to some general insights into the occurrence of clustered mutations at microsatellite loci, the utility of linked loci in studies of parentage, and the use of parentage data for direct estimation of adult population size.

Animals↗
PubMedDate not supplied

Cranial Nerve Wheel of Competencies.

BACKGROUND: The neuroscience intensive care unit (ICU) staff development committee explored ways to test cranial nerve competencies of staff. With the assistance of the nurse manager, clinical nurse specialist, and education specialist, a game called Cranial Nerve Wheel of Competencies was developed. METHOD: The game tested learners' competency knowledge of cranial nerves. Game participants had the opportunity to attend classes on cranial nerve function and to review written materials prior to the day of testing. RESULTS: Staff evaluated the testing methodology as excellent and preferable to a written test. They found the game challenged their knowledge, yet was not intimidating. CONCLUSION: Gaming as a method to test competency knowledge of cranial nerves was an exciting alternative to written testing or return demonstration.

Attitude of Health Personnel↗