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H L Parsons

Publications and source records attributed to H L Parsons.

4 recordsLinked to original sources
PubMed2000

Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin.

We determined the effect of insulin on the fate of glucose and contractile function in isolated working hypertrophied hearts from rats with an aortic constriction (n = 27) and control hearts from sham-operated rats (n = 27). Insulin increased glycolysis and glycogen in control and hypertrophied hearts. The change in glycogen was brought about by increased glycogen synthesis and decreased glycogenolysis in both groups. However, the magnitude of change in glycolysis, glycogen synthesis, and glycogenolysis caused by insulin was lower in hypertrophied hearts than in control hearts. Insulin also increased glucose oxidation and contractile function in control hearts but not in hypertrophied hearts. Protein content of glucose transporters, protein kinase B, and phosphatidylinositol 3-kinase was not different between the two groups. Thus hypertrophied hearts are less responsive to the metabolic and functional effects of insulin. The reduced responsiveness involves multiple aspects of glucose metabolism, including glycolysis, glucose oxidation, and glycogen metabolism. The absence of changes in content of key regulatory molecules indicates that other sites, pathways, or factors regulating glucose utilization are responsible for these findings.

Animals↗
PubMed1999

Increased respiratory restriction during phosphate-limited growth in transgenic tobacco cells lacking alternative oxidase.

We found that mitochondrial alternative oxidase (AOX) protein and the capacity for CN-resistant respiration are dramatically increased in wild-type tobacco (Nicotiana tabacum) suspension-cultured cells in response to growth under P limitation, and antisense (AS8) tobacco cells unable to induce AOX under these conditions have altered growth and metabolism. Specifically, we found that the respiration of AS8 cells was restricted during P-limited growth, when the potential for severe adenylate control of respiration (at the level of C supply to the mitochondrion and/or at the level of oxidative phosphorylation) is high due to the low cellular levels of ADP and/or inorganic P. As a result of this respiratory restriction, AS8 cells had altered growth, morphology, cellular composition, and patterns of respiratory C flow to amino acid synthesis compared with wild-type cells with abundant AOX protein. Also, AS8 cells under P limitation displayed high in vivo rates of generation of active oxygen species compared with wild-type cells. This difference could be abolished by an uncoupler of mitochondrial oxidative phosphorylation. Our results suggest that induction of non-phosphorylating AOX respiration (like induction of adenylate and inorganic P-independent pathways in glycolysis) is an important plant metabolic adaptation to P limitation. By preventing severe respiratory restriction, AOX acts to prevent both redirections in C metabolism and the excessive generation of harmful active oxygen species in the mitochondrion.

Amino Acids↗
PubMed1996

Directing phage selections towards specific epitopes.

It is possible to direct selections from antibody repertoires displayed on filamentous phage towards unique epitopes on protein antigens by competing with related molecules. A phage display repertoire of human single chain Fvs (scFvs) was panned three times against foetal haemoglobin (HbF). The selection was dominated by one clone with a Kd of 10 nM but yielded at least 17 others, all of which bound HbF but crossreacted with adult haemoglobin (HbA). To direct selection towards HbF-specific epitopes, the repertoire was preincubated with HbA in solution before each panning. Crossreactive scFvs can form complexes with the soluble HbA and thereby be prevented from binding the immobilized HbF. Four clones with preferential binding to HbF emerged under these conditions. One of these (Hb-1), with a Kd of 6 microM, had exquisite specificity for HbF and could distinguish cells expressing HbF from those expressing HbA by immunocytochemistry and flow cytometry. This antibody has an affinity that is 600-fold lower than the dominant crossreactive clone, and so only emerged under conditions of 'competitive deselection'. Thus, competitive deselection is a viable means for directing selections towards useful epitopes. It permits a more effective 'search' of phage display repertoires and allows the emergence of lower affinity clones with useful specificities. These clones may be useful in themselves or may serve as leads for in vitro affinity maturation.

Adult↗