Search PubMedSearch

Biomedical subjects

L Hardy

Publications and source records attributed to L Hardy.

14 recordsLinked to original sources

Biophysical mechanism of the scavenger site near T cell-presented epitopes.

We seek to identify consensus sequences in digested fragments of antigenic proteins regulating selection and major histocompatibility complex (MHC)-restricted presentation to T cells of epitopes within those fragments. One such pattern, of recurrent, hydrophobic sidechains forming a longitudinal hydrophobic strip when a sequence is coiled as an alpha-helix, is found in or near most T cell-presented epitopes. Such recurrent hydrophobicity may lead to protease-protected coiling of the fragment against endosomal membranes and transfer to MHC molecules. This concept leads to better identification of T cell-presented sequences and possible to engineering of T cell-presented vaccines to affect their potency and MHC restriction.

Amino Acid Sequence

Psychological stress, performance, and injury in sport.

This paper reviews the empirical literature on psychological stress in sport, and the effects that such stress may have upon performance, vulnerability to injury, and rehabilitation from injury. It also examines the strategies that sports performers could use to overcome these effects. The major sources of stress that have been reported by sports performers include fear of failure, concerns about social evaluation by others (particularly the coach), lack of readiness to perform, and loss of internal control over one's environment. Various models and theories of the effects of such stress upon performance and vulnerability to injury are reviewed, including multidimensional anxiety theory and a catastrophe model of anxiety and performance. The cognitive and physiological processes which are thought to underly these effects are also reviewed, together with the intervention strategies that are implied by these processes. Research on the psychological stress that appears to be experienced by performers when they are injured is very limited. However, that which is available suggests that many of the same psychological skills that are thought to enhance performance can also be used to reduce the risk of injury, and promote a speedy recovery from injury. These include goal-setting, imagery, self-talk, and relaxation skills.

Adaptation, Psychological

Highly restricted distributions of hydrophobic and charged amino acids in longitudinal quadrants of alpha-helices.

Helix formation in folding proteins is stabilized by binding of recurrent hydrophobic side chains in one longitudinal quadrant against the locally most hydrophobic region of the protein. To test this hypothesis, we fitted sequences of 247 alpha-helices of 55 proteins to the circular (infinite) template (symbol; see text) to maximize the strip-of-helix hydrophobicity index (the mean hydrophobicity of residues in (symbol; see text) positions). These template-predicted configurations closely matched crystallographic structures in 87% of four- or five-turn helices compared. We determined the longitudinal quadrant distributions of amino acids in the template-fitted, sheet projections of alpha-helices with respect to the best longitudinal, hydrophobic strip on each helix and to the N and C termini, interiors, and entire helices. Amino acids Leu, Ile, Val, and Phe were concentrated in one longitudinal quadrant (p less than 0.001). Lys, Arg, Asp, and Glu were not in the quadrant of Leu, Ile, Val, and Phe (p less than 0.001). Significant quadrant distributions for other amino acids and for termini of the helices were also found.

Amino Acids

Reoxygenation-dependent decrease in mitochondrial NADH:CoQ reductase (Complex I) activity in the hypoxic/reoxygenated rat heart.

Reoxygenation of the hypoxic myocardium results in a number of processes, including an O2-dependent increase in total tissue Ca2+ and cell lysis in which mitochondrial electron transport plays a key role. In the present study we have isolated mitochondria from perfused rat hearts subjected to hypoxia and found no change in their respiratory function relative to controls. In contrast, mitochondria isolated immediately after reoxygenation of hypoxic-perfused hearts exhibited a specific and significant decrease in NADH:CoQ reductase (Complex I; EC 1.6.5.3) activity, as measured both polarographically and spectrophotometrically. Isolated cardiomyocytes subjected to a similar protocol of hypoxia/reoxygenation also exhibited a specific decrease in Complex I activity. Myocardial perfusion with media containing Ruthenium Red protected against the reoxygenation-dependent loss of Complex I activity. These observations taken together suggest that mitochondrial Ca2+ uptake on reoxygenation is implicated in the mechanism of the specific loss of Complex I activity.

Animals

A catastrophe model of anxiety and performance.

An experiment is reported which tests Fazey & Hardy's (1988) catastrophe model of anxiety and performance. Eight experienced basketball players were required to perform a set shooting task, under conditions of high and low cognitive anxiety. On each of these occasions, physiological arousal was manipulated by means of physical work in such a way that subjects were tested with physiological arousal increasing and decreasing. Curve-fitting procedures followed by non-parametric tests of significance confirmed (p less than .002) Fazey & Hardy's hysteresis hypothesis: namely, that the polynomial curves for the increasing vs. decreasing arousal conditions would be horizontally displaced relative to each other in the high cognitive anxiety condition, but superimposed on top of one another in the low cognitive anxiety condition. Other non-parametric procedures showed that subjects' maximum performances were higher, their minimum performances lower, and their critical decrements in performance greater in the high cognitive anxiety condition than in the low cognitive anxiety condition. These results were taken as strong support for Fazey & Hardy's catastrophe model of anxiety and performance. The implications of the model for current theorizing on the anxiety-performance relationship are also discussed.

Achievement

Structure, multiple site binding, and segmental accommodation in thymidylate synthase on binding dUMP and an anti-folate.

The structure of Escherichia coli thymidylate synthase (TS) complexed with the substrate dUMP and an analogue of the cofactor methylenetetrahydrofolate was solved by multiple isomorphous replacement and refined at 1.97-A resolution to a residual of 18% for all data (16% for data greater than 2 sigma) for a highly constrained structure. All residues in the structure are clearly resolved and give a very high confidence in total correctness of the structure. The ternary complex directly suggests how methylation of dUMP takes place. C-6 of dUMP is covalently bound to gamma S of Cys-198(146) during catalysis, and the reactants are surrounded by specific hydrogen bonds and hydrophobic interactions from conserved residues. Comparison with the independently solved structure of unliganded TS reveals a large conformation change in the enzyme, which closes down to sequester the reactants and several highly ordered water molecules within a cavernous active center, away from bulk solvent. A second binding site for the quinazoline ring of the cofactor analogue was discovered by withholding addition of reducing agent during crystal storage. The chemical change in the protein is slight, and from difference density maps modification of sulfhydryls is not directly responsible for blockade of the primary site. The site, only partially overlapping with the primary site, is also surrounded by conserved residues and thus may play a functional role. The ligand-induced conformational change is not a domain shift but involves the segmental accommodation of several helices, beta-strands, and loops that move as units against the beta-sheet interface between monomers.

Binding Sites

Sports performance.

Explore the source record for details and available documents.

Biomechanical Phenomena

Neonatal hemochromatosis. Genetic analysis of transferrin-receptor, H-apoferritin, and L-apoferritin loci and of the human leukocyte antigen class I region.

Neonatal hemochromatosis (NH), a generally fatal disorder of infancy, is characterized by severe hepatic insufficiency of intrauterine onset and by marked organ iron loading. Its cause is unknown. It has been suggested that NH may represent an unusual manifestation of hereditary hemochromatosis (HH), which is human leukocyte antigen (HLA) linked. Evidence for major rearrangements or deletions at the HLA class I region and at three loci directly involved in iron metabolism (H- and L-apoferritin and the transferrin receptor [TfR]) was sought. The population studied included five probands with NH and 14 first-degree family members in a total of six kindreds. Also sought were HLA associations with NH by collating the results of HLA serotyping in these 19 persons and in 17 members of 7 additional kindreds in which NH has occurred, including 5 probands with NH and 12 first-degree family members. We found no evidence for major rearrangements or deletions in H- or L-apoferritin genes, in TfR genes, or within the HLA locus. We found no evidence for linkage of NH to HLA serotypes. We conclude that while NH and HH are similar in their patterns of iron loading, they are not genetically related.

Adult

Group psychotherapy in the treatment of adolescent and preadolescent military dependents with recurrent diabetic ketoacidosis.

The adolescent military dependent with recurrent diabetic ketoacidosis (DKA) is a difficult management problem. Career relocations and an absentee sponsor frequently preclude family-oriented interventions. We recently treated four patients with recurrent DKA who had failed to improve following intensive medical and educational programs. They were enrolled into weekly outpatient group psychotherapy in addition to routine medical management. Three out of the four patients improved in compliance and had a decrease in the frequency or severity of DKA. This approach may be effective when individual psychotherapy or lengthy hospitalization are either too far removed or too costly.

Adolescent

Stress and cognitive functioning in sport.

This paper considers the relationship between stress and cognitive functioning and discusses some of the concepts and methods that may be adopted to examine the relationship between stress and sports performance. It considers only that literature that may be relevant to, or furthers, the understanding of sports performance under competitive stress. One of the most popular approaches has been to explain the relationship in terms of the unidimensional inverted-U hypothesis. The validity of this approach to explaining sports performances in specific situations is discussed and it is generally concluded that the inverted-U hypothesis is too vague and simplistic. The discussion considers multidimensional approaches and discusses the suitability and implications of some more recent and more complex models of stress and performance which are now available in the psychological literature. It is concluded that the relationship between stress and sports performance is an extremely complex one and involves the interaction between the nature of the stressor, the cognitive demands of the task being performed and the psychological characteristics of the individuals performing it.

Cognition

Effects of high intensity canoeing training on fibre area and fibre type in the latissimus dorsi muscle.

A high intensity short duration exercise training programme was undertaken by nine subjects on three occasions each week for nine weeks. Muscle samples from the latissimus dorsi were taken by needle biopsy, at rest, before and after training. The results revealed that there was no change in either Type I or Type II muscle fibre distribution following training. Type I fibre area did not alter significantly as a result of the training stress. Mean cross-sectional area of Type II fibres was 82 per cent greater post-training than pre-training.

Adult

Effect of growth conditions on the formation of extracellular lipoteichoic acid by Streptococcus mutans BHT.

Streptococcus mutans BHT was grown in a chemostat with glucose limitation and at defined dilution rates and pH values. Lipoteichoic acid was estimated by determining the ability of dilutions of culture fluid to sensitize erythrocytes. The greatest amounts of extracellular lipoteichoic acid were produced by organisms growing at a low dilution rate and at pH 6.0 or 6.5. To enable a more accurate estimation of the total amount of extracellular material, rocket immunoelectrophoresis was employed. These results confirmed that the greatest amounts of reactive material were produced by slow-growing organisms, although there were discrepancies between these results and those obtained by hemagglutination. The extracellular material was fractionated by column chromatography and membrane ultrafiltration to yield a lipoteichoic acid-containing fraction and a presumptive deacylated lipoteichoic acid fraction. The relative proportions detected by rocket immunoelectrophoresis differed with the growth conditions, particularly the dilution rate. Analysis of the phenol-extracted cellular material also indicated the presence of deacylated lipoteichoic acid, although less than in the culture fluid.

Glucose

Effect of carbohydrate source and growth conditions on the production of lipoteichoic acid by Streptococcus mutans Ingbritt.

Streptococcus mutans Ingbritt was grown in a chemostat at defined dilution rates and pH values and under carbohydrate limitation. At a constant dilution rate of D = 0.1 h-1 and with either 0.5% glucose or 0.5% sucrose, the amounts of both cellular and extracellular lipoteichoic acid increased as the culture pH increased from 5.0 to 7.5. At a constant pH of 6.0, the amount of cellular lipoteichoic acid formed by cultures growing in 0.2% or 0.5% glucose was relatively constant over a range of dilution rates, although the amount of extracellular lipoteichoic acid formed in 0.2% glucose at intermediate dilution rates was less than that formed in 0.5% glucose. Organisms grown in 0.5% sucrose at pH 6.0 contained increasing amounts of cellular lipoteichoic acid as the dilution rate was increased. A comparison of the amounts of cellular lipoteichoic acid formed by organisms growing at D = 0.5 h-1 and pH 6.0 in glucose, sucrose, fructose, or mixtures of glucose and fructose in limiting amounts suggested that the enhanced production of lipoteichoic acic by sucrose-grown organisms was due to the fructose component. The culture fluids from both glucose- and sucrose-grown organisms contained detectable amounts of serotype c antigen, whereas glucose-grown cultures also contained significant amounts of an extracellular hexose-containing polymer.

Animals