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Biomedical subjects

G B Jones

Publications and source records attributed to G B Jones.

At least 19 recordsLinked to original sources

Adenylated dinucleotide binding to the adenosine 5',5'''-P1,P4-tetraphosphate mouse heart receptor.

We have demonstrated specific adenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) receptors at heart cell surfaces. Optimal Ap4A binding requires receptor activation. Other Investigators have demonstrated that Ap5A and Ap6A act as vasopressors. We now compare the binding of Ap4A, Ap5A and Ap6A on heart membranes to determine if all three ligands bind to the same receptor and their relative avidities. Anti-Ap4A receptor antibodies inhibit the binding of all three ligands. SDS-PAGE analysis of Ap4A, Ap5A and Ap6A cross-linked to membranes reveals that all three are attached to a 30 kDa peptide. The specific activity for binding to unactivated membranes is similar for all three ligands. However, after receptor activation there is a 3.4x increase in Ap4A binding and a 32.5x decrease in the KD; values remain unchanged for Ap5A and Ap6A. These data indicate that Ap4A, Ap5A and Ap6A bind to the same receptor on cardiac membranes but receptor activation enhances only Ap4A binding.

Animals

The non-covalent interaction of pyrrolo[2, 1-c] [1, 4]benzodiazepine-5, 11-diones with DNA.

A series of 15 pyrrolo[2, 1-c] [1, 4]benzodiazepine-5, 11-diones has been synthesized and evaluated for in vitro DNA binding by thermal denaturation and fluorescence quenching studies with calf thymus (CT) DNA. The results indicate that two compounds of the series, 7 and 8, elevate the melting point of DNA by 2.9 +/- 0.6 and 3.3 +/- 0.8 K, respectively. Similarly, a significant quenching of the fluorescence of the dihydroxy analogue 8 was observed upon interaction with CT-DNA. As controls, the dihydroxy isomer 9 with the reverse stereochemistry at C2 and the non-substituted parent dilactam 12, failed to increase the DNA melting point or exhibit significant quenching upon interaction with DNA. In addition, preliminary experiments with GC- and AT-rich polymers suggest some sequence-dependent properties for dilactams 7 and 8. Overall, these results indicate a highly specific structural requirement for DNA binding. Molecular modelling with d(GTAGATC), d(GCAGATC) and d(GCGTAGC) duplex sequences has provided a model based on hydrogen bonding between the dihydroxy dilactam 8 and DNA, that rationalizes some of the results obtained. It is possible that the observed interactions represent the non-covalent (binding) component of the interaction of covalently-bonding anthramycin-type anti-tumour antibiotics with DNA.

Anthramycin

Low-iodine diet for producing iodine deficiency in rats.

A low-iodine diet has been prepared for rats, using locally available low-iodine ingredients. On analysis it has been shown to consistently contain 15-20 ng iodine/g. When fed to growing female rats, this diet produced severe iodine deficiency while not significantly affecting growth or reproduction. The deficiency was manifested by a fall in daily urinary iodine excretion (to less than 1 microgram/day) and a seven-fold increase in thyroid uptake (131I) observable within 3 months. Levels of plasma thyroxine (T4) and thyroid stimulating hormone (TSH) continued to change for 4-5 months, T4 falling from 69.9 to 7.5 nmol/l and TSH increasing seven-fold from a control value of 364 to 2406 ng/ml. Goitre was present in all iodine-deficient rats and iodine content in the thyroid was 10% of the control value.

Animal Feed

Production of severe iodine deficiency in sheep using a prepared low-iodine diet.

Extensive tests on dietary materials suitable for ingestion by sheep have led to the preparation of an appropriate diet which, when fed to the sheep, caused severe iodine deficiency. The deficiency was manifested by daily urinary excretion values which fell to levels of less than 20 micrograms iodine and by thyroxine (T4) and triiodothyronine (T3) concentrations in blood plasma which were reduced from more than 90 and 1.80 nmol/l to the low levels of less than 2.58 and 0.31 nmol/l respectively. The values were attained 5 months after feeding the low-iodine diet. Goitre was present in most of the animals and the reductions in T4 and T3 values were accompanied by increased concentrations of plasma thyroid stimulating hormone (TSH) from less than 8.6 to more than 68 ng/ml. Samples of wool removed from selected areas of the sheep showed that the iodine-deficient diet also caused a reduction in the growth of wool.

Animals

Precision stereotaxic procedure for the mouse (Mus musculus): method and instrumentation.

A precision stereotaxic procedure for mouse brain research is described accompanied by a new design in mouse stereotaxic head holder and a new device used to guarantee accurate alignment of the skull in the stereotaxic device. This method and instrumentation when applied in forthcoming research will contribute to the development of investigations of structure/function relationship in mouse brain.

Animals