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Biomedical subjects

W R Gray

Publications and source records attributed to W R Gray.

At least 73 records · Page 4Linked to original sources
PubMed1985

A sleep-inducing peptide from Conus geographus venom.

A novel peptide toxin, which causes a sleep-like state upon intracerebral injection in mice, has been purified to homogeneity from the venom of the piscivorous marine snail Conus geographus L. It elicits no obvious effects when injected i.p. into either mice or fish. The purified toxin is a highly acidic heptadecapeptide with no cystine residues (Lys1, Arg1, Asx2, Ser1, Glx7-8, Gly1, Ile1, Leu2). This composition is in marked contrast to those of other conotoxins, which are basic and disulphide-bridged. The N-terminal residue is Gly and the COOH-terminal sequence is Ser-Asn-NH2.

Amino Acids↗
PubMed1984

Gamma-carboxyglutamate in a neuroactive toxin.

The venom of a fish-hunting cone snail (Conus geographus) contains a novel toxin, the "sleeper" peptide, which induces a sleep-like state in mice when injected intracerebrally. We demonstrate that this peptide contains 5 mol of gamma-carboxyglutamate (Gla) in 17 amino acids. The amino acid sequence of the sleeper peptide is Gly-Glu-Gla-Gla-Leu-Gln-Gla-Asn-Gln-Gla-Leu-Ile-Arg-Gla-Lys-Ser-Asn-NH2.

1-Carboxyglutamic Acid↗
PubMed1984

Purification and sequence of a presynaptic peptide toxin from Conus geographus venom.

A novel toxin, omega-conotoxin (omega-CgTX), from the venom of the fish-eating marine mollusc Conus geographus has been purified and biochemically characterized. Recently, this omega-conotoxin has been shown to inhibit the voltage-activated entry of Ca2+, thus providing a potentially powerful probe for exploring the vertebrate presynaptic terminal [Kerr, L. M., & Yoshikami, D. (1984) Nature (London) 308, 282-284]. The toxin is a basic 27 amino acid peptide amide with three disulfide bridges. An unusual feature is a remarkable preponderance of hydroxylated amino acids. The sequence of omega-CgTx GVIA is Cys-Lys-Ser- Hyp-Gly5-Ser-Ser-Cys-Ser-Hyp10-Thr-Ser-Tyr-Asn-Cys15-C ys-Arg-Ser- Cys-Asn20-Hyp-Tyr-Thr-Lys-Arg25-Cys-Tyr-NH2.

Amino Acid Sequence↗
PubMed1984

Structural characterization of the isoforms of neonatal and adult rat liver metallothionein.

Metallothionein was purified from the livers of adult and neonatal rats. The complete amino acid sequences of isoforms I and II of Cd-induced adult metallothionein were determined by automated Edman degradation of CNBr and tryptic peptides of carboxymethylated proteins. Both isoproteins contain 61 residues, but differ at 12 of those positions. The positions of the 20 cysteinyl residues are invariant with respect to those in other known mammalian metallothioneins. Based on the following criteria, the two soluble and constitutive Zn-metallothionein isoforms from neonatal liver appear identical to their corresponding forms in the adult animal: 1) they behave identically on reverse-phase high-pressure liquid chromatography, anion-exchange chromatography and nondenaturing gel electrophoresis; 2) their amino acid compositions are the same within experimental error; and 3) their amino acid sequences are identical in the first 23 residues, even though isoforms I and II differ in 7 of those positions. It appears highly likely that isoforms from both neonatal and adult rats are encoded by the same genes, and therefore that the large age-dependent concentration differences seen in the liver must be due to variation in gene regulation.

Age Factors↗
PubMed1984

Conotoxin GI: disulfide bridges, synthesis, and preparation of iodinated derivatives.

The 13 amino acid toxic peptide from the marine snail Conus geographus, conotoxin GI, blocks the acetylcholine receptor at the neuromuscular junction. In this report, we describe a method for analyzing disulfide bonding in nanomole amounts of small cystine-rich peptides. The procedure involves partial reduction and a double-label alkylation of cysteine residues. Using this method, we show that the natural conotoxin GI has a (2-7, 3-13) disulfide configuration. The structure of conotoxin GI has been confirmed by chemical synthesis. The preparation and purification of molecularly homogeneous, iodinated derivatives of this toxin are also described. All derivatives, including the [diiodohistidine,diiodotyrosine]conotoxin GI, retained at least half of the biological activity of unmodified toxin. Since the tetraiodinated toxin, which is greater than 25% by weight iodine, retains considerable toxicity, unmodified histidine and tyrosine residues in conotoxin GI are not crucial for biological activity.

Amino Acid Sequence↗
PubMed1984

Spontaneous remission and its significance for trials in primary prevention of hypertension.

The hypothesis that salted food can cause hypertension must be tested prospectively to see if unsalted food protects non-hypertensive persons. The first of two feasibility studies has confirmed that established hypertension can show spontaneous remission on unsalted food. We now report the preliminary findings of a second feasibility study to test whether a clinic for hypertension can attract self-referred non-hypertensive people interested in preventing hypertension by changing their diet. A total of 874 applicants have attended at least one pre-entry visit. We report data from the first 176 participants who completed the feasibility study lasting 12 weeks. Of these 110 were non-hypertensive people and 93 (84.5%) would be prepared to remain on unsalted food for five years.

Adolescent↗
PubMed1983

Conotoxin MI. Disulfide bonding and conformational states.

The toxic peptide from Conus magus venom (conotoxin MI) is a 14-amino acid peptide (McIntosh, M., Cruz, L. J., Hunkapiller, M. W., Gray, W. R., and Olivera, B. M. (1982) Arch. Biochem. Biophys. 218, 329-334) which inhibits the acetylcholine receptor. In this work we have confirmed the primary structure and established the disulfide bonding configuration (Cys 3-Cys 8; Cys 4-Cys 14) by direct chemical synthesis of the toxin with specific disulfide bridges. Natural and synthetic toxins were compared by several methods. Fast atom bombardment mass spectroscopy confirmed that the synthetic product had the expected molecular mass and number of exchangeable hydrogens. Ultraviolet CD spectra were closely comparable in shape and magnitude for the two materials, which were also identical in biological activity and chromatographic behavior. We have also established that, although the peptide is highly cross-linked with two disulfide bridges, it can slowly equilibrate between two conformations. A simulation analysis suggests that the conformers have half-lives of approximately 12 and approximately 72 min at 0 degrees C, decreasing approximately 2-fold for every 10 degrees C increase in temperature.

Amino Acid Sequence↗
PubMed1982

Randomised controlled trial of a no-added-sodium diet for mild hypertension.

90 patients on medication for mild hypertension were randomly allocated to diet and control groups and kept under surveillance by their own doctors every 2 weeks for 12 weeks to test the short-term effectiveness of a diet free from sodium additives as an alternative to medication. Mean urinary sodium excretion was reduced 37.0 mmol/24 h in the diet group and 161.0 mmol/24 h in the control group, with average K/Na ratios of 3.9 and 0.50. Both groups had a fall in mean systolic and diastolic blood pressure, but the diet group finished on half of the initial amount of medication, with 1 patient in 3 off medication and 4 out of 5 having either stopped or reduced the dose. The control group remained on almost the full amount of medication, with 2 patients out of 3 having made no reduction. The diet group had a mean weight loss of 2.1 kg, a rise in serum potassium, and a fall in serum bicarbonate. There was no increase in overall frequency of muscle cramp, and the diet group reported feeling happier, less depressed, and less dependent on analgesics. Two-thirds of the diet group intend to continue to diet indefinitely. Reduction of sodium intake permitted drug treatment to be substantially reduced without side-effects or loss of blood-pressure control.

Adult↗
PubMed1982

Third component of human complement: localization of the internal thiolester bond.

Human complement protein C3 was inactivated by using methylamine and thereby generating a SH group from the internal thiol ester. The protein was coupled via this SH group to activated thiol-Sepharose and digested with elastase. Fragment C3d remained attached to the thiol-Sepharose and was subsequently eluted with L-cysteine. Concomitantly, the original SH group was regenerated, and it was then labeled with iodo[2-(3)H]acetic acid. Partial sequence analysis of the radiolabeled C3d fragment showed that both components of the thiol ester are located close to the amino terminus (residues 23 and 26). Specific chemical cleavage of the alpha-chain was achieved after S-cyanylation of the thiol. The two fragments obtained corresponded to the amino-terminal section (M(r) approximately 46,000) and the carboxy-terminal section (M(r) approximately 70,000). These results together indicate that fragment C3d occupies approximately positions 345-610 of the alpha-chain. The partial sequence of C3d was extended by completion of the sequence of a previously described tryptic peptide. Comparison of residues 1-49 of C3d with a peptide from alpha(2)-macroglobulin [Swenson, R. P. & Howard, J. B. (1980) J. Biol. Chem. 255, 8087-8091] shows a previously recognized identity of seven residues around the thiol ester site and a second region of identity around a known glycosylation site of alpha(2)-macroglobulin. The relationships among these proteins and protein C4 are discussed. An overall outline of the structure of C3 is presented, showing the locations of various fragments and cleavage sites. The thiol ester group places constraints on the local folding of the peptide chain; a possible conformation is suggested and discussed in relation to the mechanism of activation.

Amino Acid Sequence↗
PubMed1981

Peptide toxins from Conus geographus venom.

Three homologous toxic peptides which cause postsynaptic inhibition at the vertebrate neuromuscular junction have been purified from the venom of the marine snail Conus geographus. Their amino acid sequences are: (formula see text) The biologically active peptides are monomeric, with internal disulfide bonds.

Amino Acid Sequence↗
PubMed1979

Studies on the evolution of elastin--I. Phylogenetic distribution.

1. Aortae and other tissues from numerous animals were examined for the presence of the rubbery protein elastin by (a) chemical purification and amino acid analysis, (b) presence of the cross-linking amino acids desmosine and isodesmosine and (c) histological staining. 2. Elastin was found in all vertebrates examined (42 species) with the exception of cyclostomes (3 species). It was absent from all invertebrates tested (14 species). 3. The amino acid compositions of vertebrate elastins showed marked and interesting interspecies variations.

Amino Acids↗
PubMed1978

Pharyngeal aspiration in normal adults and patients with depressed consciousness.

A sensitive technic using indium111 chloride was devised to investigate the occurrence of pharyngeal aspiration. Twenty normal subjects and 10 patients with depressed consciousness were studied. Forty-five per cent of the normal subjects aspirated during deep sleep. Normal subjects who did not aspirate were noted to sleep poorly. Seventy per cent of the patients with depressed consciousness aspirated. Aspiration of pharyngeal secretions occurs frequently in patients with depressed sensorium and also in normal adults during deep sleep. Bacterial pneumonia may result when aspirated bacteria are not effectively cleared. This may result when clearance mechanisms are impaired or when they are overwhelmed by large volumes of aspirated secretions.

Adult↗