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Biomedical subjects

J R Payne

Publications and source records attributed to J R Payne.

14 recordsLinked to original sources

The impact of ACE genotype on serum ACE activity in a black South African male population.

The strong association between the angiotensin I-converting enzyme (ACE) gene I/D polymorphism with serum ACE activity appears lacking in Nigerians and Kenyans, but has not previously been well assessed in others of African origin. This study addressed this issue in an ethnically well defined black South African population. A putative association for the A22982G ACE gene variant, a QTL likely to impact on serum ACE activity, was also sought. Subjects were 200 healthy male black South African volunteers from the Xhosa ethnic group. Venous blood was obtained from all subjects for DNA extraction. ACE I/D and A22982G genotypes were determined and serum ACE activity measured. Age and blood pressure were recorded. For the group as a whole (mean +/- SD age 38.5 +/- 9.8 years, SBP 119.6 +/- 14.1 mmHg, DBP 78.2 +/- 10.1 mmHg) serum ACE activity was 38.2 +/- 11.2 nmol ml(-1)min(-1). ACE I/D genotype was not significantly associated with serum ACE activity. In contrast, the A22982G variant was significantly associated with serum ACE activity, being 35.9 +/- 9.6, 38.1 +/- 10.6 and 42.4 +/- 15.3 nmol ml(-1)min(-1) for AA, AG and GG genotypes respectively; p = 0.03 by ANOVA and p = 0.01 by linear trend. In keeping with the findings in some other African populations, the ACE I/D polymorphism is not strongly associated with serum ACE activity in Xhosa South Africans. As such, it cannot be used as a marker of ACE activity in these subjects. In this regard the use of the A22982G gene variant may be more appropriate.

Black People↗

Left ventricular growth response to exercise and cigarette smoking: data from LARGE Heart.

BACKGROUND: Increasing left ventricular mass is a risk factor for cardiovascular morbidity and mortality. OBJECTIVE: To examine the possible association of smoking with the left ventricular growth response in men. METHODS: Left ventricular mass was measured in 309 army recruits before and after an identical 12-week physical training programme. Left ventricular mass was determined using cardiovascular magnetic resonance. RESULTS: Left ventricular mass increased with training (mean (standard deviation (SD)) 3.83 (10.81) g, p<0.001). By univariate analysis, exercise-induced change in left ventricular mass was positively associated with cigarette smoking (mean (SD) 1.69 (11.10) g v 4.76 (10.23) g for non-smokers v ex- and current smokers, respectively; p = 0.026), whereas age, height, diastolic and systolic blood pressure (SBP), alcohol consumption or indices of physical activity were not significantly associated with change in left ventricular mass. Multivariate analysis showed body weight, smoking status and SBP to be independent predictors of left ventricular mass (incremental R(2) = 3.4%, p = 0.004; R(2) = 4.9%, p = 0.024; and R(2) = 1.7%, p = 0.041, respectively). CONCLUSIONS: Cigarette smoking and SBP are associated with exercise-induced left ventricular growth in young men. The positive association of smoking with changes in left ventricular mass is surprising, given the limited exposure of these subjects to smoking, and although these data do not prove causation, they are of great interest to those trying to uncover the drivers of left ventricular hypertrophy, as well as to those examining the possible ill-effects of smoking in the young.

Analysis of Variance↗

The -344T>C promoter variant of the gene for aldosterone synthase (CYP11B2) is not associated with cardiovascular risk in a prospective study of UK healthy men.

INTRODUCTION: The tissue renin-angiotensin system is implicated in the pathogenesis of coronary artery disease (CAD). As locally synthesised aldosterone is a potential mediator of CAD, we have sought an association of the -344T>C variant of the aldosterone synthase (CYP11B2) gene with CAD events. METHODS: Subjects comprised of the Second Northwick Park Heart Study (NPHSII), a prospective study of unrelated, healthy middle-aged Caucasian males. CAD events were recorded in 2490 subjects, and defined as a sudden cardiac death, myocardial infarction or coronary artery revascularisation procedure. Mean follow-up was 10.8 years. Aldosterone synthase genotype was determined in 2490 subjects. Power calculation suggests that we have 80% power (at a significance level of 0.05) to detect a difference in hazard ratio (HR) between homozygote groups of 0.45. RESULTS: One hundred and eighty-seven CAD events were recorded in 2490 subjects. In the group overall, CAD events were independent of genotype with adjusted hazard ratios being 1.00 versus 1.25 versus 0.80 for TT versus TC versus CC genotypes, respectively, P = 0.07. Genotype interactions with smoking and blood pressure were sought. Whilst CAD events were independent of genotype amongst non-smokers, CC genotype in smokers was associated with a reduced risk HR 2.02 versus 2.28 versus 0.82 for TT versus TC versus CC genotypes, P = 0.05 (HR for TT + TC versus CC were 1.77 versus 0.67, P = 0.02). This apparent interaction remained after adjustment for conventional risk factors. No such interaction was found with blood pressure. CONCLUSIONS: Aldosterone synthase genotype is unrelated to overall CAD events risk. A possible interaction with smoking requires confirmation.

Analysis of Variance↗

Cardiac effects of anabolic steroids.

Anabolic steroid abuse in athletes has been associated with a wide range of adverse conditions, including hypogonadism, testicular atrophy, impaired spermatogenesis, gynaecomastia, and psychiatric disturbance. But what effect does steroid abuse have on the cardiovascular system?

Anabolic Agents↗

Characterization and modeling of P-type electrosensory afferent responses to amplitude modulations in a wave-type electric fish.

The first stage of information processing in the electrosensory system involves the encoding of local changes in transdermal potential into trains of action potentials in primary electrosensory afferent nerve fibers. To develop a quantitative model of this encoding process for P-type (probability-coding) afferent fibers in the weakly electric fish Apteronotus leptorhynchus, we recorded single unit activity from electrosensory afferent axons in the posterior branch of the anterior lateral line nerve and analyzed responses to electronically generated sinusoidal amplitude modulations of the local transdermal potential. Over a range of AM frequencies from 0.1 to 200 Hz, the modulation transfer function of P-type afferents is high-pass in character, with a gain that increases monotonically up to AM frequencies of 100 Hz where it begins to roll off, and a phase advance with a range of 15-60 degrees. Based on quantitative analysis of the observed gain and phase characteristics, we present a computationally efficient model of P-type afferent response dynamics which accurately characterizes changes in afferent firing rate in response to amplitude modulations of the fish's own electric organ discharge over a wide range of AM frequencies relevant to active electrolocation.

Action Potentials↗

Logarithmic time course of sensory adaptation in electrosensory afferent nerve fibers in a weakly electric fish.

1. We recorded single unit activity from individual primary electrosensory afferent axons in the posterior branch of the anterior lateral line nerve of gymnotid weakly electric fish, Apteronotus leptorhynchus. We analyzed the responses of P-type (probability-coding) afferent fibers to externally applied amplitude step changes in the quasi-sinusoidal transdermal potential established by the fish's own electric organ discharge (EOD). 2. In response to AM step increases in transdermal potential, the firing rate of P-type afferents exhibited an abrupt increase followed by an initially rapid and subsequently more gradual decay back toward the baseline level. Afferent responses continued to adapt slowly throughout the duration of prolonged step stimuli lasting > 100 s. The time course of sensory adaptation was similar for all units tested. 3. We introduce a new functional form for describing the time course of sensory adaptation in which the change in firing rate delta r decays logarithmically with time: delta r(t) = A/[B In (t) + 1]. This logarithmic form accurately describes the adaptation time course of P-type afferents over five decades in time, from milliseconds to hundreds of seconds, with only two free parameters. Using a nonlinear least-squares fitting technique, we obtained a mean value of the parameter B, which characterizes the adaptation time course, of 0.149 +/- 0.028 (mean +/- SD, n = 49). 4. We compare logarithmic fits with traditional multiexponential and power law forms and demonstrate that the logarithmic form yields a better characterization of P-type afferent responses. This analysis helps explain the variability in previously reported adaptation time constants, which have ranged from 0.2 to 3.4 s, in gymnotid P-type afferents. 5. We tested the linearity of P-type afferent responses using positive and negative AM steps of varying amplitudes. Aside from nonlinearities associated with rectification (firing rates cannot be negative) and saturation (firing rates cannot exceed the EOD frequency), we found that P-type afferent responses scaled linearly with stimulus amplitude. 6. Based on the observed linearity, we predict the frequency domain response characteristics of P-type afferents and find that the predicted gain and phase are in good agreement with experimental measurements using sinusoidal AM stimuli over a range of AM frequencies from 1 to 100 Hz. Thus the logarithmic parameterization of the step appears to accurately capture the response dynamics of P-type afferents over a wide range of behaviorally relevant AM frequencies. 7. We conclude that the temporal filtering properties of pyramidal cells in the medullary electrosensory nucleus, the electrosensory lateral line lobe (ELL), need to be reevaluated in light of the logarithmic adaptation time course in the periphery, and we discuss implications for the role of P-type afferents in driving a feedback gain control mechanism that regulated ELL pyramidal cell responsiveness.

Action Potentials↗

Physiological and developmental implications of motor unit anatomy.

There is increasing evidence that the architectural design and arrangement of the fibers within a motor unit have important physiological and developmental ramifications. Limited data, however, are available to directly address this issue. In the present study the physiological properties of one motor unit in each of seven cat tibialis anterior (TA) muscles were determined. Each of these units then was repetitively stimulated to deplete the glycogen in all muscle fibers within the unit. Subsequently, the length, type of ending, and spatial distribution of fibers sampled from these physiologically and histochemically typed motor units were determined. Four fast fatigable (FF), one fast, fatigue resistant (FR), and two slow (S) motor units (MU) were studied. The samples consisted of all those glycogen-depleted fibers (9-27) contained within a single fascicle or a circumscribed area of each of the motor unit territories. The mean fiber lengths for the two slow motor units were 35.9 and 45.5 mm. The mean fiber lengths for the fast motor unit samples ranged from 8.8 to 48.5 mm. Some fibers of both the fast and slow units reached lengths of 58 mm. Most of the fibers in the slow units extended the entire distance between the proximal and distal musculotendinous planes, had relatively constant cross-sectional areas, and terminated at the tendon as blunt endings. In contrast, the majority of the fibers in the fast units terminated intrafascicularly at one end, and the cross-sectional area decreased progressively along their lengths, that is, showed a tapering pattern for a significant proportion of their lengths. Therefore, the force generated by units that end midfascicularly would appear to be transmitted to connective tissue elements and/or adjacent fibers. All fibers of a fast unit within a fascicle were located at approximately the same proximo-distal location. Thus, developmentally the selection of muscle fibers by a motoneuron would seem to be influenced by their spatial distribution. The architectural complexities of motor units also have clear implications for the mechanical interactions of active and inactive motor units. For example, the tension capabilities of a motor unit may be influenced not only by the spatial arrangement of its own fibers, but also by the level of activation of neighboring motor units.

Animals↗

Bovine parafilariasis: condemnations at the Cato Ridge abattoir.

Evidence presented shows a 585% increase in the compounded total carcase condemnations for parafilariasis at the Cato Ridge abattoir in the year July 1981/June 1982 as compared with July 1979/June 1980. There is also evidence which points to condemnations occurring in bi-annual cycles with peaks in November/December and June.

Abattoirs↗

13C NMR spectroscopy of labeled pyridoxal 5'-phosphate. Model studies, D-serine dehydratase, and L-glutamate decarboxylase.

Pyridoxal 5'-phosphate labeled to the extent of 90% with 13C in the 4' (aldehyde) and 5' (methylene) positions has been synthesized. 13C NMR spectra of this material and of natural abundance pyridoxal 5'-phosphate are reported, as well as 13C NMR spectra of the Schiff base formed by reaction of pyridoxal 5'-phosphate with n-butylamine, the secondary amine formed by reduction of this Schiff base, the thiazolidine formed by reaction of pyridoxal 5'-phosphate with cysteine, the hexahydropyrimidine formed by reaction of pyridoxal 5'-phosphate with 1,3-diaminobutane, and pyridoxamine 5'-phosphate. The range of chemical shifts for carbon 4' in these compounds is more than 100 ppm, and thus this chemical shift is expected to be a sensitive indicator of structure in enzyme-bound pyridoxal 5'-phosphate. The chemical shift of carbon 5', on the other hand, is insensitive to these structure changes. 13C NMR spectra have been obtained at pH 7.8 and 9.4 for D-serine dehydratase (Mr = 46,000) containing natural abundance pyridoxal 5'-phosphate and containing 13C-enriched pyridoxal 5'-phosphate. The enriched material contains two new resonances not present in the natural abundance material, one at 167.7 ppm with a linewidth of approximately 24 Hz, attributed to carbon 4' of the Schiff base in the bound coenzyme, and one at 62.7 Hz with a linewidth of approximately 48 Hz attributed to carbon 5' of the bound Schiff base. A large number of resonances due to individual amino acids are assigned. The NMR spectrum changes only slightly when the pH is raised to 9.4. The widths of the two enriched coenzyme resonances indicate that the coenzyme is rather rigidly bound to the enzyme but probably has limited motional freedom relative to the protein. 13C NMR spectra have been obtained for L-glutamate decarboxylase containing natural abundance pyridoxal 5'-phosphate and 13C-enriched pyridoxal 5'-phosphate. Under conditions where the two enriched 13C resonances are clearly visible in D-serine dehydratase, no resonances are visible in enriched L-glutamate decarboxylase, presumably because the coenzyme is rigidly bound to the protein and the 300,000 molecular weight of this enzyme produces very short relaxation times for the bound coenzyme and thus very broad lines.

Binding Sites↗

Performance of chicks fed diets formulated to minimize excess levels of essential amino acids.

Studies were conducted in which levels of essential amino acids in excess of the minimum requirements were minimized in broiler diets composed of commercially available feed stuffs and synthetic amino acid supplements. Growth rate and efficiency of feed utilization of chicks fed such diets were equal to that attained by chicks fed diets formulated by conventional means when grown under conditions where heat stress was not a factor and significantly improved when fed under conditions of heat stress. Improvements were obtained in efficiency of protein and calorie utilization using this technique of formulation.

Amino Acids, Essential↗