Biomedical subjects

S J Hodges

Publications and source records attributed to S J Hodges.

22 records · Page 2Linked to original sources

PubMed1988

Circulating vitamin K levels in patients with fractures.

It is now clear that vitamin K1 is part of a biochemical cycle that is essential for the conversion of specific bone peptides into a form that can bind calcium. We have used a recently described procedure for assaying vitamin K1 in plasma to test the involvement of this vitamin in fracture healing. Markedly depressed circulating levels were found in patients with fractures and the time taken for this level to return to normal appeared to be influenced by the severity of the fracture.

Adolescent↗

PubMed1987

Cobra cardiotoxins. Purification, effects on skeletal muscle and structure/activity relationships [published errtum appears in Eur J Biochem 1988 Feb 1;171(3):727].

A new preparative method for isolating homogeneous cardiotoxins from cobra venoms is described. The technique, based on reverse-phase high-pressure liquid chromatography, was used to isolate eight cardiotoxins of known sequence from four different venoms. In each case the method was found to be particularly efficient at removing trace quantities of contaminating phospholipase. Cardiotoxins isolated in this manner were found to retain their full biological activity. Without exception the purified cardiotoxins lacked powerful haemolytic activity at concentrations up to 0.01 mM (about 100 micrograms ml-1), although some lysis of human erythrocytes was induced at higher concentrations. The cardiotoxins displayed a wide range of depolarizing activity on cultured skeletal muscle, the lowest activity being associated with the highest LD50 value. Correlating variations in amino acid sequence and variations in depolarization potency revealed the importance of residues in the second and third loops, especially lysine-46, serine-48 and lysine-52, together with a number of hydrophobic residues. Further modifications of pharmacological activity were associated with the presence of additional basic residues in the first and second loops and to minor differences in secondary structure.

Amino Acid Sequence↗

PubMed1985

Molecular conformation of alpha-bungarotoxin as studied by nuclear magnetic resonance and circular dichroism.

We have examined the circular dichroism and nuclear magnetic resonance spectra of a long neurotoxin, alpha-bungarotoxin, over a wide range of pH values and temperatures, and under high salt conditions. The observations are interpreted partly in terms of the known crystal structure of this polypeptide. We support earlier findings of a greater degree of beta-sheet structure in solution than has been reported by X-ray crystallography and, importantly, the invariant residue associated with neurotoxicity, Trp29, is shown to be in a similar environment to that found in alpha-cobratoxin and LS III from Laticauda semifasciata. The implications of this observation for structure/function relationships are outlined.

Amino Acid Sequence↗

PubMed1984

Structure-activity studies of homologues of short chain neurotoxins from Elapid snake venoms.

Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata) were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer cervicis nerve-muscle preparations. All three homologues had acetylcholine receptor blocking activity, as they abolished responses to indirect stimulation, acetylcholine and carbachol but had no effect on responses to direct muscle stimulation. CM10 was only about 5 times less potent than the short neurotoxin CM14; S5C10 and CM12 were respectively 30 and 300 times less active. The block induced by the three homologues, but not by the neurotoxins, was readily reversed by washing. CM10 and CM12 had virtually identical c.d. spectra which were closely similar to those of the neurotoxins. The spectrum of S5C10 indicated changes in the environment of tyrosine-25 and in the position of tryptophan-29. These alterations could distort the 3-dimensional arrangement of the residues postulated to form the receptor binding site. The results with CM10 and CM12 highlight a role for the first loop (residues 6-16) in the binding of neurotoxins to acetylcholine receptors, in addition to the previously postulated reactive site.

Animals↗