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Biomedical subjects

A Halsall

Publications and source records attributed to A Halsall.

7 recordsLinked to original sources
PubMed1999

Intrinsic helical propensities and stable secondary structure in a membrane-bound fragment (S4) of the shaker potassium channel.

The location and stability of helical secondary structure in a fragment comprising an extended sequence of the S4 transmembrane segment of the Shaker potassium channel was determined in methanol, and when bound to vesicles composed of egg phosphatidylcholine: egg phosphatidylglycerol (4:1; mol:mol) in water. The N-acetylated, C-amidated peptide corresponds to the sequence comprising residues A355-I384 in the Shaker potassium channel. Although NOEs characteristic of helical structure encompass essentially the full peptide sequence in methanol, analysis of amide and CH(alpha) chemical shifts, and amide exchange protection factors establish that stable helical structure comprises only around the first 22 amino acids of the 30 residue peptide. This sequence corresponds to that predicted to have the highest helical stability in water, indicating that while helical structure is considerably stabilised in methanol, the relative helical propensities of amino acids in methanol may be similar to those in water. In the presence of vesicles containing negatively charged lipids, helical structure corresponding to a maximum of around 40 % of the extended S4 peptide is induced; no helical structure is induced in the presence of vesicles composed only of neutral lipids. The location of stable helical structure in the membrane-bound peptide was determined by amide hydrogen-deuterium exchange trapping, and was shown to encompass the sequence between residues near M2 and I18. This sequence is similar to that having high helix propensity in water and methanol, supporting the idea that intrinsic helical propensities are important in defining the location of stable helical structure in polypeptides bound in the interfacial region of lipid bilayers. The study defines an approach to determining the location of, and contributions to, the stability of helical secondary structure in membrane-reconstituted polypeptides.

Amino Acid Sequence↗
PubMed1994

Role of protein synthesis and of fatty acid metabolism in the longer-term regulation of pyruvate dehydrogenase kinase.

Antibodies were raised in rabbits to free rat liver pyruvate dehydrogenase (PDH) kinase alpha-chain and shown to react with PDH kinase alpha-chain in rat heart and liver PDH complexes, in purified pig heart PDH complex and in bovine kidney dihydrolipoamide acetyltransferase-protein X-PDH kinase subcomplex. E.l.i.s.a for PDHE1 (pyruvate dehydrogenase) and PDH kinase have been developed and applied to assays of these proteins in extracts of rat liver and rat heart mitochondria; the measured immunoreactivities for PDHE1 (heart > liver) and for PDH kinase alpha-chain (liver > heart) paralleled known differences in PDH complex and PDH kinase activities respectively. The results of e.l.i.s.a of PDH kinase alpha-chain in extracts of rat liver mitochondria showed that the effects of starvation to increase PDH kinase activity in vivo, and the effects of dibutyryl cyclic AMP or palmitate to increase PDH kinase activity in hepatocytes cultured in vitro, are due largely (> 90%) to an increase in the specific activity of PDH kinase. The effect, in cultured hepatocytes, of dibutyryl cyclic AMP to increase PDH kinase activity was blocked by cycloheximide; the effect of palmitate was blocked by an inhibitor of carnitine palmitoyltransferase I (Etomoxir), but not by cycloheximide.

Animals↗
PubMed1994

Glucose fatty acid interactions and the regulation of glucose disposal.

Glucose is essential for the energy metabolism of some cells and conservation of glucose is obligatory for survival during starvation. The principal site of this glucose conservation is the mitochondrial pyruvate dehydrogenase (PDH) complex, which is regulated by reversible phosphorylation (phosphorylation is inactivating). In cells in which glucose oxidation is switched off during starvation, fatty acids are used as fuel, and acetyl CoA and NADH formed by beta-oxidation promote phosphorylation of PDH complex by activation of PDH kinase. A longer-term mechanism further increases PDH kinase activity in response to cAMP and products of beta-oxidation of fatty acids. Coordinated inhibition of glycolytic flux mediated by effects of citrate on PFK1 and PFK2 in muscles and liver results in an associated inhibition of glucose uptake. Similar mechanisms lead to impaired glucose oxidation in diabetes.

Animals↗
PubMed1994

Mechanisms modifying glucose oxidation in diabetes mellitus.

The Glucose Fatty Acid Cycle as formulated 30 years ago and reviewed in the Minkowski lecture in 1966 described short term effects of fatty acids (minutes) to decrease uptake, glycolysis and oxidation of glucose in heart and skeletal muscles. Such short term effects have since been extended to include inhibition of glucose uptake and glycolysis and stimulation of gluconeogenesis in liver and these effects have also been convincingly demonstrated in man in vivo. More recently a longer term effect of fatty acid metabolism to decrease glucose oxidation (hours) has been shown in heart and skeletal muscle and liver. This effect increases the specific activity of pyruvate dehydrogenase kinase, which in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex. Activity of the pyruvate dehydrogenase complex is the major determinant of glucose oxidation rate. It seems likely that longer term effects of fatty acids on this and other aspects of glucose metabolism could be important in the development of insulin resistance in diabetes mellitus in man.

Animals↗
PubMed1979

A double-blind trial of a single intravenous dose of metronidazole as prophylaxis against wound infection following appendicectomy.

One hundred patients undergoing appendicectomy through a right iliac fossa incision were randomized to receive normal saline or 500 mg metronidazole as an intravenous infusion during the operation. One patient in the saline group developed an erythematous rash. There were 13 wound infections (as defined by the discharge of pus), 12 (out of 51) in the saline group and 1 (out of 49) in the metronidazole group. Bacteroides spp. were frequently cultured from the lumen of removed appendices and from pus obtained from infected wounds. This work supports the value of metronidazole but suggests that a single-dose regimen is adequate for prophylaxis.

Adolescent↗
PubMed1978

A prospective study of subclavian vein catheters used exclusively for the purpose of intravenous feeding.

One hundred and seventy-eight central venous catheters inserted via the subclavian vein for the purposes of intravenous feeding were studied in 77 patients. Insertion of the catheter was complicated by puncture of the subclavian artery on three occasions and by a pneumothorax on two. Catheters remained in situ for a mean period of 10 days. Ninety-two were removed because the requirement for nutrition no longer existed and 86 were removed because of suspected infection, venous thrombosis or mechanical problems. Infective organisms were grown from 17 catheters (9.5 per cent) but other unrelated causes of infection were frequently present in the population under study. Venous thrombosis of a major upper limb vein was seen in 8 patients.

Adolescent↗