PubMed Health⌕ Search

Biomedical subjects

N A Johnson

Publications and source records attributed to N A Johnson.

At least 19 recordsLinked to original sources
PubMed2006

Effect of altered pre-exercise carbohydrate availability on selection and perception of effort during prolonged cycling.

This study assessed the effect of altered carbohydrate (CHO) availability on self-selected work rate during prolonged time-trial cycling. Eight endurance-trained men undertook two experimental cycling time-trials after glycogen-depleting exercise and 2 days of: (a) high (9.3 +/- 0 g CHO kg(-1) day(-1)) (HC) and (b) low CHO intakes (0.6 +/- 0.1 g CHO kg(-1) day(-1)) (LC), via a double-blinded crossover design. All feedback regarding performance was removed during both exercise trials. Self-selected external power output was not different during the first 2 h of exercise between experimental conditions (P > 0.05), despite reported sensations of increased tiredness before and during exercise, significantly reduced whole body CHO oxidation (P < 0.05), plasma lactate concentrations (P < 0.05) and earlier onset of fatigue during exercise in LC versus HC. Perceived exertion was not different throughout exercise between conditions (P > 0.05). Mean power output declined significantly in LC versus HC (P < 0.05) after approximately 2 h of exercise, and was associated with significant reductions in cadence, heart rate and plasma glucose concentration (P < 0.05). These results demonstrate that when compared with time-trial cycling performed after a HC diet, reduced CHO availability does not initially alter self-selected work rate in endurance athletes who are deceived of their CHO status prior to exercise. This finding suggests that reduced work rate during exercise following lowered CHO intake may, in part, be a consequence of the subject's awareness of dietary CHO restriction rather than solely a physiologically mediated action. Further research is required to distinguish the influence of circulating glucose and peripheral glycogen availability on pacing strategy during prolonged exercise.

Adaptation, Physiological↗
PubMed2006

Short-term suppression of plasma free fatty acids fails to improve insulin sensitivity when intramyocellular lipid is elevated.

AIMS: Metabolic responses to manipulation of the plasma free fatty acid (FFA) concentration were assessed in six healthy men via cross-over design to determine whether FFAs independently influence insulin sensitivity. METHODS: Intramyocellular lipid (IMCL) was measured by proton magnetic resonance spectroscopy and insulin sensitivity via frequently sampled intravenous glucose tolerance test (IVGTT) after 67 h of two identical low carbohydrate/high fat (LC) diets which were used to elevate IMCL and plasma FFAs. To uncouple the influence of FFAs and IMCL on insulin sensitivity, FFAs were suppressed 30 min prior to and during IVGTT in one treatment [LC + nicotinic acid (NA)] by NA ingestion. RESULTS: Vastus lateralis IMCL was significantly elevated in LC (13.3 +/- 1.1 x 10(-3)) and LC + NA (13.5 +/- 1.1 x 10(-3)) (P < 0.01 for both), but was not different between conditions (P > 0.05). Plasma FFAs were raised in LC (0.79 +/- 0.08 mmol/l) and LC + NA (0.80 +/- 0.11 mmol/l) (P < 0.01 for both) and were significantly reduced by NA ingestion prior to (0.36 +/- 0.05 mmol/l, P < 0.01) and during IVGTT (P < 0.05) in LC + NA. Despite marked differences in plasma FFA availability, insulin sensitivity and glucose tolerance were not different between LC and LC + NA (P > 0.05 for both). CONCLUSIONS: Plasma FFAs appear to exert no immediate effect on insulin sensitivity/glucose tolerance independent of their action on intracellular lipid moieties. Further research is required to elucidate the duration of FFA suppression required to restore insulin sensitivity following lipid-induced insulin resistance.

Adult↗
PubMed2004

Alkyl hydroperoxide peroxidase subunit C (ahpC) protects against organic peroxides but does not affect the virulence of Porphyromonas gingivalis W83.

The cloned Porphyromonas gingivalis alkyl hydroperoxide reductase (ahpC) gene complemented an ahpC defect in Escherichia coli. To study the role of ahpC in protecting against oxidative stress in P. gingivalis a 1.8 kb fragment containing the ahpC gene was amplified from the chromosome of P. gingivalis W83. This gene was insertionally inactivated using the ermF-ermAM antibiotic resistance cassette and used to create a ahpC-deficient mutant by allelic exchange. One mutant strain, designated FLL141, demonstrated no change in the growth rate, black pigmentation, beta-hemolysis or level of proteolytic activity compared to the parent strain. Although P. gingivalis FLL141 was more sensitive to hydrogen peroxide than the parent strain, there was no change in its virulence potential in the mouse model compared to the wild-type strain. These findings suggest that the ahpC gene plays a role in peroxide resistance in P. gingivalis but does not contribute significantly to virulence.

Alleles↗
PubMed2004

8-oxo-7,8-dihydroguanine is removed by a nucleotide excision repair-like mechanism in Porphyromonas gingivalis W83.

A consequence of oxidative stress is DNA damage. The survival of Porphyromonas gingivalis in the inflammatory microenvironment of the periodontal pocket requires an ability to overcome oxidative stress caused by reactive oxygen species (ROS). 8-oxo-7,8-dihydroguanine (8-oxoG) is typical of oxidative damage induced by ROS. There is no information on the presence of 8-oxoG in P. gingivalis under oxidative stress conditions or on a putative mechanism for its repair. High-pressure liquid chromatography with electrochemical detection analysis of chromosomal DNA revealed higher levels of 8-oxoG in P. gingivalis FLL92, a nonpigmented isogenic mutant, than in the wild-type strain. 8-oxoG repair activity was also increased in cell extracts from P. gingivalis FLL92 compared to those from the parent strain. Enzymatic removal of 8-oxoG was catalyzed by a nucleotide excision repair (NER)-like mechanism rather than the base excision repair (BER) observed in Escherichia coli. In addition, in comparison with other anaerobic periodontal pathogens, the removal of 8-oxoG was unique to P. gingivalis. Taken together, the increased 8-oxoG levels in P. gingivalis FLL92 could further support a role for the hemin layer as a unique mechanism in oxidative stress resistance in this organism. In addition, this is the first observation of an NER-like mechanism as the major mechanism for removal of 8-oxoG in P. gingivalis.

DNA Damage↗
PubMed2003

Insulin resistance and elevated triglyceride in muscle: more important for survival than "thrifty" genes?

Elevated intramyocellular triglyceride (IMTG) is strongly associated with insulin resistance, though a cause and effect relationship has not been fully described. Insulin sensitivity and IMTG content are both dynamic and can alter rapidly in response to dietary variation, physical activity and thermoregulatory response. Physically active humans (athletes) display elevated IMTG content, but in contrast to obese persons, are insulin sensitive. This paradox has created confusion surrounding the role of IMTG in the development of insulin resistance. In this review we consider the modern athlete as the physiological archetype of the Late Palaeolithic hunter-gatherer to whom the selection pressures of food availability, predation and fluctuating environmental conditions applied and to whom the genotype of modern man is virtually identical. As food procurement by the hunter-gatherer required physical activity, "thrifty" genes that encouraged immediate energy storage upon refeeding after food deprivation (Neel, 1962) must have been of secondary importance in survival to genes that preserved physical capacity during food deprivation. Similarly genes that enabled survival during cold exposure whilst starved would be of primary importance. In this context, we discuss the advantage afforded by an elevated IMTG content, and how under these conditions, a concomitant muscle resistance to insulin-mediated glucose uptake would also be advantageous. In sedentary modern man, adiposity is high and skeletal muscle appears to respond as if a state of starvation exists. In this situation, elevated plasma lipids serve to accrue lipid and induce insulin resistance in skeletal muscle. Reversal of this physiological state is primarily dependent on adequate contractile activity, however, in modern Western society, physical inactivity combined with abundant food and warmth has rendered IMTG a redundant muscle substrate.

Animals↗
PubMed2002

Intramyocellular triacylglycerol in prolonged cycling with high- and low-carbohydrate availability.

Vastus lateralis intramyocellular lipid (IMCL) content was assessed by (1)H-magnetic resonance spectroscopy before and after prolonged time trial cycling bouts of approximately 3-h duration. Six highly trained male cyclists completed a double-blind, randomized, crossover design of two experimental trials after a strenuous exercise bout and 48 h of high (HC) (9.32 +/- 0.08 g. kg(-1). day(-1)) and low (LC) (0.59 +/- 0.21 g. kg(-1). day(-1)) dietary carbohydrate. Resting IMCL content was significantly higher after LC vs. HC (P < 0.01) and was reduced during exercise by 64 and 57%, respectively. IMCL was not different between conditions after exercise (P > 0.05). The approximately twofold increase in IMCL degradation in LC compared with HC suggests that higher rates of whole body lipid metabolism in LC were in part attributable to a greater IMCL utilization. Four subjects experienced reductions of IMCL in excess of 70% during exercise. To our knowledge, this is the first study to report near depletion of IMCL during prolonged cycling, indicating that IMCL, presumably the triacylglycerol component, may be exhausted by prolonged strenuous exercise.

Adult↗
PubMed2001

Toward a new synthesis: population genetics and evolutionary developmental biology.

Despite the recent synthesis of developmental genetics and evolutionary biology, current theories of adaptation are still strictly phenomenological and do not yet consider the implications of how phenotypes are constructed from genotypes. Given the ubiquity of regulatory genetic pathways in developmental processes, we contend that study of the population genetics of these pathways should become a major research program. We discuss the role divergence in regulatory developmental genetic pathways may play in speciation, focusing on our theoretical and computational investigations. We also discuss the population genetics of molecular co-option, arguing that mutations of large effect are not needed for co-option. We offer a prospectus for future research, arguing for a new synthesis of the population genetics of development.

Adaptation, Biological↗
PubMed2000

Rapid speciation via parallel, directional selection on regulatory genetic pathways.

Regulatory genetic pathways are ubiquitous in organisms and play a central role in the realization of the phenotype during development. We explored the proposition that these pathways can provide a plausible source of the epistatic variation that has been implicated in the evolution of postzygotic reproductive isolation. We modeled gene regulation as a matching function between the product of one locus and the promoter site of the next locus in the pathway, with binding strength determining the amount of product. When the phenotype is subject to parallel selection in a pair of independent populations, we find that the fitnesses of F(1)and F(2)hybrids often drop to very low values as the populations respond in genetically different and incompatible ways. The simulations support the predictions of the analytical models. Hybrid fitness reduction occurs more often as the number of loci in the pathway increases, and as the binding site interactions become more complex. Less hybrid fitness reduction is seen when the populations start with imperfect binding in the pathway. In contrast, when we constructed the phenotype without gene regulation using multiplicative rules, isomorphic to the additive phenotype commonly assumed in evolutionary models, we found no appreciable F(1)fitness reduction and only slight F(2)fitness reduction. The interaction of genetic drift and mutation, even at very high rates, did not reduce hybrid fitness at all on the time-scales we considered. Clearly, the evolution of regulatory genetic pathways can play an important role in speciation, but much more empirical information is needed on the effect of allelic variability in regulatory site interactions before this role is fully understood.

Animals↗
PubMed2000

Three words three shapes: A clinical test of memory.

Three Words - Three Shapes was designed as an easy "bedside" test for elderly patients that assesses verbal and nonverbal memory within the same modality. In the present study, it was administered to patients with probable Alzheimer's disease (PRAD), a control group of non-demented older subjects (NC) and a group of patients with Korsakoff's amnesia (KA). Incidental recall and several other measures of learning, retention and recognition differentiated control from PRAD and KA subjects. PRAD and KA subjects' performance was similar, but there were some material-specific interactions. This test is relatively easy and some of the derived measures could prove useful in staging amnesia progression beyond the earliest stages of PRAD when more difficult tests yield floor effects.

Aged↗
PubMed1999

A two-component affinity chromatography purification of Helix pomatia arylsulfatase by tyrosine vanadate.

The inhibition of Helix pomatia arylsulfatase by the synergistic combination of N-acetyl-l-tyrosine ethyl ester and vanadate has been extended to affinity chromatography for purification. In the presence of vanadate, l-tyrosine ethyl ester (TEE), immobilized on CH-Sepharose 4B retained arylsulfatase from the digestive juice or lyophilized powder of H. pomatia. No enzyme was retained without vanadate or with arsenate or phosphate. Arylsulfatase was eluted from the column matrix by removing the vanadate to less than 50 microM with buffer containing EDTA to chelate the vanadate. Escherichia coli alkaline phosphatase and potato acid phosphatase, two enzymes which are inhibited by vanadate but not by the vanadate-TEE complex, were not retained by the immobilized TEE under any conditions used. The sulfatase activity was completely separated from contaminating glucuronidase activity present in the crude enzyme extracts. The Ki for the immobilized vanadate-TEE system was found to be 5.0 x 10(-7) M with a capacity of 25 mg/ml swollen gel. A purification of greater than 40-fold from the lyophilized powder of H. pomatia (Sigma Type H-5) was achieved using this technique. The Ki/Keq of other phenols with vanadate were determined in a 96-well plate format as an example of a rapid screening technique that could be extended to other phosphoryl and sulfuryl-transfer enzyme classes.

Animals↗
PubMed1999

Validity of unbound digoxin measurements by immunoassays in presence of antidote (Digibind).

Measurement of unbound digoxin in presence of Fab fragments may be useful in management of overdoses. The analysis can be performed on serum directly or on ultrafiltrate of serum. The architecture of the immunoassay may influence the validity of results obtained using these two approaches. We tested this hypothesis by preparing serum mixtures containing various concentrations of digoxin and Digibind and analyzed them by the immunoassays before and after ultrafiltration. Four samples collected from Digibind-treated patients were also analyzed before and after ultrafiltration. The slopes and the y-intercepts of the measured versus the expected values for serum and its ultrafiltrate overlapped for the MEIA digoxin assay. For other three immunoassays tested (ACS:180, Stratus, and On-Line), either the slope or the intercept for measured versus the expected results for serum were significantly different (P < 0.05) than those for ultrafiltrate. Following addition of digoxin and Digibind, differences in results for serum analyzed directly or after ultrafiltration were < 0.50 ng/ml. Comparable samples from digoxin-overdosed patients treated with Digibind had differences of > 1.0 ng/ml. Previous claims reporting direct analysis of digoxin in presence of antidote but not having used patient samples for validation should be revisited. To date, analysis of serum ultrafiltrate by an immunoassay proven not to have matrix bias remains the most accurate approach in measuring unbound digoxin in presence of antidote.

Adult↗
PubMed1999

Simultaneous rapid measurement of whole blood myoglobin, creatine kinase MB, and cardiac troponin I by the triage cardiac panel for detection of myocardial infarction.

This multicenter study evaluated the Biosite Triage(R) Cardiac Panel as a quantitative, multimarker, whole blood system for the detection of acute myocardial infarction (MI). Optimum cutoffs for the discrimination of acute MI (n = 192 patients, 59 with MI) as determined by ROC curve analyses were as follows: 0.4 microgram/L for cardiac troponin I (cTnI); 4.3 microgram/L for the creatine kinase MB isoenzyme (CK-MB); and 107 microgram/L for myoglobin. The Triage Panel showed the following concordances for detection or rule-out of MI compared with established devices: cTnI >89%; CK-MB >81%; myoglobin >69%. No significant differences were present between methods for the same marker. Diagnostic efficiencies demonstrated comparable sensitivities and specificities for the diagnosis of MI in patients presenting with symptoms compared with the Dade, Beckman, and Behring CK-MB, cTnI, and myoglobin assays; the ratio of sensitivity to specificity for each marker was as follows: cTnI, 98%:100%; CK-MB, 95%:91%; myoglobin, 81%:92%. The areas under the ROC curves for the Biosite myoglobin, CK-MB, and cTnI were 0.818, 0.905, and 0.970, respectively; the areas were significantly different, P <0.05. In patients with skeletal muscle injury and renal disease, the Triage cTnI showed 94% and 100% specificity, respectively. The Triage panel offers clinicians a whole blood, point-of-care analysis of multiple cardiac markers that provides excellent clinical sensitivity and specificity for the detection of acute MI.

Creatine Kinase↗
PubMed1998

The population genetics of synthetic lethals.

Synthetic lethals are variants at different loci that have little or no effect on viability singly but cause lethality in combination. The importance of synthetic lethals and, more generally, of synthetic deleterious loci (SDL) has been controversial. Here, we derive the expected frequencies for SDL under a mutation-selection balance for the complete haploid model and selected cases of the diploid model. We have also obtained simple approximations that demonstrate good fit to exact solutions based on numerical iterations. In the haploid case, equilibrium frequencies of carrier haplotypes (individuals with only a single mutation) are comparable to analogous single-locus results, after allowing for the effects of linkage. Frequencies in the diploid case, however, are much higher and more comparable to the square root of the single-locus results. In particular, when selection operates only on the double-mutant homozygote and linkage is not too tight, the expected frequency of the carriers is approximately the quartic root of the ratio between the mutation rate and the selection coefficient of the synthetics. For a reasonably wide set of models, the frequencies of carriers can be on the order of a few percent. The equilibrium frequencies of these deleterious alleles can be relatively high because, with SDL, both dominance and epistasis act to shield carriers from exposure to selection. We also discuss the possible role of SDL in maintaining genetic variation and in hybrid breakdown.

Diploidy↗
PubMed1998

Quality of life and later adverse health outcomes in patients with suspected heart attack.

We tested the hypothesis that low quality of life (QOL) after discharge from hospital with ischaemic heart disease (IHD) is associated with higher rates of later adverse outcomes (death and subsequent hospital admission for acute myocardial infarction or congestive cardiac failure). Three hundred and seventy-five patients previously enrolled in an intervention study which assessed QOL six months after hospitalisation were followed up for an additional 18 months. The rates of adverse outcomes increased as QOL decreased (high QOL 9%; moderate 18%; low 28%). After adjustment for known prognostic factors, the risk of an adverse outcome was still higher in 'low' and 'moderate' compared to 'high' QOL subjects (low QOL adjusted OR = 2.6, 95% CI = 1.2-5.8; moderate 1.9, 0.8-4.2). In conclusion, QOL after discharge from hospital appears to be an independent predictor of later morbidity and mortality.

Adult↗
PubMed1997

Genetic variation segregating in natural populations of Tribolium castaneum affecting traits observed in hybrids with T. freemani.

We investigated patterns of within-species genetic variation for traits observed in hybrids (hybrid numbers, hybrid sex ratios, and hybrid male deformities) between two species of flour beetles, Tribolium castaneum and T. freemani. We found genetic variation segregating among four natural populations of T. castaneum as well as within these populations. For some hybrid traits, we observed as much variation among populations 750 km apart as between populations on different continents, suggesting genetic differentiation at a local scale. Within natural populations, the variation segregating among sires is greater than that found in an earlier study for an outbred laboratory population and comparable to that observed between inbred lines derived from the outbred stock by eight generations of brother-sister mating. When sires from T. castaneum are mated to conspecific and heterospecific females, we do not observe a significant correlation at the level of the family mean between the intraspecific and interspecific phenotypes, suggesting the independence of the hybrid traits from comparable traits within species. We discuss our findings in relation to the evolutionary genetics of speciation and the expression of epistatic genetic variance in interspecific crosses.

Animals↗
PubMed1997

The history of the Army weight standards.

Medical officers in the U.S. Army are tasked with screening, evaluating, and processing soldiers in accordance with AR 600-9, the Army's height and weight standards regulation. This essay traces the origins of the Army's weight standards to the present day. The Army's height and weight standards have varied markedly, from the crude subjective assessment of selective service candidates at the local draft examination boards at the turn of the century to the modern, highly accurate methods currently used in anthropomorphic research. The strictness of military recruitment and retention standards closely paralleled changing military personnel requirements in any particular era. Racial integration and the influx of women into the ranks had noteworthy effects on this history. The evolution of the Army's weight-control program and screening standards reflects advancements in medical knowledge and technology, societal and political pressure, and the empirical tests of world wars.

Anthropometry↗