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Biomedical subjects

J C Smith

Publications and source records attributed to J C Smith.

At least 127 records · Page 7Linked to original sources
PubMed1999

Critical power is related to cycling time trial performance.

The purpose of this study was to evaluate critical power (W(CP)) as an indicator of aerobic fitness in trained cyclists, and to determine its relationship to cycling time trial (TT) performance. Thirteen competitive USCF category 2 or 3 cyclists provided season's best 40 km TT times (mean [SD]) time = 59.6 min (3.1), and performed two 17 km TT under controlled conditions (26.6 min [1.1]). Ventilatory threshold (VT) and VO2max were determined from a maximal incremental test. W(CP) was calculated using the results of four all-out constant power tests. Mean W(CP) was 299 (61) W or 4.1 W x kg(-1), VT was 3616 (750) ml x min(-1) or 49.8 ml x kg(-1) x min(-1) (7.5), and VO2max was 4596 ml x min(-1) or 63.5 ml x kg(-1) x min(-1) (8.0). W(CP) was strongly related to VT and VO2max, demonstrating that it can serve as a measure of aerobic fitness in this population. Expressions of W(CP) were slightly to considerably more highly related to 17 km and 40 km TT performances (r = -0.77 to -0.91) than were expressions of VT and VO2max (r = -0.71 to -0.87). It is concluded that W(CP) provides an aerobic fitness measure for competitive cyclists which can be obtained without invasive testing. In addition, W(CP) is strongly related to the TT performance of competitive cyclists.

Adult↗
PubMed1999

Vitamin A and zinc supplementation of preschool children.

OBJECTIVE: To determine whether supplementation of vitamin A and/or zinc (Zn) improved serum levels of these nutrients and/or height and weight gains in preschool children, 22 to 66 months, living in Belize, Central America. METHODS: Subjects received either Zn, vitamin A, Zn and vitamin A or a placebo, (70 mg Zn and/or 3030 RE vitamin A, once per week) for 6 months in a 2x2 factorial design. Forty-three children, from a population of 104 prescreened, completed the study; they were selected, prior to treatment, for low/marginal serum concentrations of these micronutrients. RESULTS: Serum Zn levels were greater (16%, p<0.001) for those who received Zn. In contrast, after vitamin A treatment there were no differences in serum vitamin A among groups. Although increases in height (+4.4 cm, p<0.001) and weight (+0.79 kg, p<0.001), compared with baseline values, were numerically greatest for children who received both supplements, only the vitamin A supplementation effect was significant, resulting in increased height (+1.4 cm, p<0.002) and greater weight gain (+0.15 kg, p<0.03) compared to those receiving no vitamin A. Vitamin A supplementation alone significantly increased (p<0.001) hemoglobin concentration. CONCLUSION: The results suggest that the preschool children in this study, prescreened for low/marginal serum concentrations from a larger population prior to treatment, were enduring inadequate vitamin A and, to a lesser degree, Zn nutriture. Height and weight gain were significantly increased in the subjects who received a single weekly supplement 3030 RE of vitamin A.

Belize↗
PubMed1999

Beta-carotene 15,15'-dioxygenase activity is responsive to copper and iron concentrations in rat small intestine.

OBJECTIVE: Previous in vitro studies have suggested that beta-carotene 15,15'-dioxygenase is an iron-dependent enzyme. However, in vivo, it is difficult to alter iron tissue concentration by varying dietary iron because of homeostatic control. On the other hand, an interaction between iron and copper has been shown, i.e., copper-deficiency results in an increase of iron in rat liver. Therefore, we hypothesized that intestinal iron concentration could be increased by copper-deficiency. Our objective was to examine the effects of iron as affected by dietary copper on beta-carotene 15,15'-dioxygenase activity in the small intestine. METHODS: Weanling male Sprague-Dawley rats (40 to 45g) were divided into four dietary groups: two copper-adequate groups (6.0 microg Cu/g diet) and two copper-deficient groups (0.6 microg Cu/g) combined with either normal iron (44 microg Fe/g) or high iron (87 microg Fe/g). Iron and copper concentrations were determined by atomic absorption spectrophotometry and the dioxygenase activity by reverse phase HPLC. RESULTS: Intestinal copper concentration was significantly reduced (40%) by the consumption of the copper-deficient diets, but intestinal iron was not changed by doubling dietary iron in rats fed either copper-adequate or copper-deficient diets. However, as hypothesized, the two copper-deficient groups exhibited higher intestinal iron concentration (> or =137%, p<0.001) than the copper-adequate controls. In addition, intestinal beta-carotene 15,15'-dioxygenase activity was increased by 27% and 106%, respectively, for copper-deficient rats fed either normal or high iron diets, compared to the respective copper-adequate controls (p<0.01). The dioxygenase activity was not significantly affected by dietary iron in either copper-adequate or copper-deficient groups. Finally, the enzyme activity was positively correlated (r=0.67, p<0.0001) with iron concentration and negatively correlated (r=-0.49, p<0.01) with copper concentration in small intestine. CONCLUSIONS: Intestinal beta-carotene 15,15'-dioxygenase may be an iron-dependent enzyme sensitive to copper status in vivo.

Analysis of Variance↗
PubMed1999

Determination of critical power by pulmonary gas exchange.

Although the physiological underpinnings of critical power (CP) have yet to be fully elucidated, it has been proposed that CP demarcates the heavy and severe exercise intensity domains and that each domain is associated with a different pattern of metabolic response and mechanism of fatigue. Severe intensity has been defined such that, during exercise at intensities above CP, the slow component of the VO2 response will drive VO2 to VO2max at the point of fatigue. In this study, two parameters were derived for each of 8 participants: (a) CP, the asymptote of the relationship between power and time to exhaustion, and (b) a related parameter; CP', the asymptote of the relationship between power and time to VO2max. CP' theoretically represents the threshold intensity above which VO2max will be elicited during exercise of sufficient duration. Participants performed two exhaustive tests at CP. There were three important findings: First, there was a practice effect on time to exhaustion at CP, and times increase 27% in the second test. Second, both CP and CP' could be obtained with good precision. Third, and most important, CP was equal to CP', thereby providing a physiological description of the mathematically derived CP parameter. It was concluded that VO2max cannot be elicited at intensities equal to or less than CP.

Adult↗
PubMed1999

Models of respiratory rhythm generation in the pre-Bötzinger complex. I. Bursting pacemaker neurons.

A network of oscillatory bursting neurons with excitatory coupling is hypothesized to define the primary kernel for respiratory rhythm generation in the pre-Bötzinger complex (pre-BötC) in mammals. Two minimal models of these neurons are proposed. In model 1, bursting arises via fast activation and slow inactivation of a persistent Na+ current INaP-h. In model 2, bursting arises via a fast-activating persistent Na+ current INaP and slow activation of a K+ current IKS. In both models, action potentials are generated via fast Na+ and K+ currents. The two models have few differences in parameters to facilitate a rigorous comparison of the two different burst-generating mechanisms. Both models are consistent with many of the dynamic features of electrophysiological recordings from pre-BötC oscillatory bursting neurons in vitro, including voltage-dependent activity modes (silence, bursting, and beating), a voltage-dependent burst frequency that can vary from 0.05 to >1 Hz, and a decaying spike frequency during bursting. These results are robust and persist across a wide range of parameter values for both models. However, the dynamics of model 1 are more consistent with experimental data in that the burst duration decreases as the baseline membrane potential is depolarized and the model has a relatively flat membrane potential trajectory during the interburst interval. We propose several experimental tests to demonstrate the validity of either model and to differentiate between the two mechanisms.

Animals↗
PubMed1999

Models of respiratory rhythm generation in the pre-Bötzinger complex. II. Populations Of coupled pacemaker neurons.

We have proposed models for the ionic basis of oscillatory bursting of respiratory pacemaker neurons in the pre-Bötzinger complex. In this paper, we investigate the frequency control and synchronization of these model neurons when coupled by excitatory amino-acid-mediated synapses and controlled by convergent synaptic inputs modeled as tonic excitation. Simulations of pairs of identical cells reveal that increasing tonic excitation increases the frequency of synchronous bursting, while increasing the strength of excitatory coupling between the neurons decreases the frequency of synchronous bursting. Low levels of coupling extend the range of values of tonic excitation where synchronous bursting is found. Simulations of a heterogeneous population of 50-500 bursting neurons reveal coupling effects similar to those found experimentally in vitro: coupling increases the mean burst duration and decreases the mean burst frequency. Burst synchronization occurred over a wide range of intrinsic frequencies (0.1-1 Hz) and even in populations where as few as 10% of the cells were intrinsically bursting. Weak coupling, extreme parameter heterogeneity, and low levels of depolarizing input could contribute to the desynchronization of the population and give rise to quasiperiodic states. The introduction of sparse coupling did not affect the burst synchrony, although it did make the interburst intervals more irregular from cycle to cycle. At a population level, both parameter heterogeneity and excitatory coupling synergistically combine to increase the dynamic input range: robust synchronous bursting persisted across a much greater range of parameter space (in terms of mean depolarizing input) than that of a single model cell. This extended dynamic range for the bursting cell population indicates that cellular heterogeneity is functionally advantageous. Our modeled system accounts for the range of intrinsic frequencies and spiking patterns of inspiratory (I) bursting cells found in the pre-Bötzinger complex in neonatal rat brain stem slices in vitro. There is a temporal dispersion in the spiking onset times of neurons in the population, predicted to be due to heterogeneity in intrinsic neuronal properties, with neurons starting to spike before (pre-I), with (I), or after (late-I) the onset of the population burst. Experimental tests for a number of the model's predictions are proposed.

Animals↗
PubMed1999

Induction of the mesendoderm in the zebrafish germ ring by yolk cell-derived TGF-beta family signals and discrimination of mesoderm and endoderm by FGF.

The endoderm forms the gut and associated organs, and develops from a layer of cells which emerges during gastrula stages in the vertebrate embryo. In comparison to mesoderm and ectoderm, little is known about the signals which induce the endoderm. The origin of the endoderm is intimately linked with that of mesoderm, both by their position in the embryo, and by the molecules that can induce them. We characterised a gene, zebrafish gata5, which is expressed in the endoderm from blastula stages and show that its transcription is induced by signals originating from the yolk cell. These signals also induce the mesoderm-expressed transcription factor no tail (ntl), whose initial expression coincides with gata5 in the cells closest to the blastoderm margin, then spreads to encompass the germ ring. We have characterised the induction of these genes and show that ectopic expression of activin induces gata5 and ntl in a pattern which mimics the endogenous expression, while expression of a dominant negative activin receptor abolishes ntl and gata5 expression. Injection of RNA encoding a constitutively active activin receptor leads to ectopic expression of gata5 and ntl. gata5 is activated cell-autonomously, whereas ntl is induced in cells distant from those which have received the RNA, showing that although expression of both genes is induced by a TGF-beta signal, expression of ntl then spreads by a relay mechanism. Expression of a fibroblast growth factor (eFGF) or a dominant negatively acting FGF receptor shows that ntl but not gata5 is regulated by FGF signalling, implying that this may be the relay signal leading to the spread of ntl expression. In embryos lacking both squint and cyclops, members of the nodal group of TGF-beta related molecules, gata5 expression in the blastoderm is abolished, making these factors primary candidates for the endogenous TGF-beta signal inducing gata5.

Activins↗
PubMed1999

Bix4 is activated directly by VegT and mediates endoderm formation in Xenopus development.

The maternal T-box gene VegT, whose transcripts are restricted to the vegetal hemisphere of the Xenopus embryo, plays an essential role in early development. Depletion of maternal VegT transcripts causes embryos to develop with no endoderm, while vegetal blastomeres lose the ability to induce mesoderm (Zhang, J., Houston, D. W., King, M. L., Payne, C., Wylie, C. and Heasman, J. (1998) Cell 94, 515-524). The targets of VegT, a transcription activator, must therefore include genes involved both in the specification of endoderm and in the production of mesoderm-inducing signals. We recently reported that the upstream regulatory region of the homeobox-containing gene Bix4 contains T-box binding sites. Here we show that expression of Bix4 requires maternal VegT and that two T-box binding sites are necessary and sufficient for mesodermal and endodermal expression of reporter genes driven by the Bix4 promoter in transgenic Xenopus embryos. Remarkably, a single T-box binding site is able to act as a mesoderm-specific enhancer when placed upstream of a minimal promoter. Finally, we show that Bix4 rescues the formation of endodermal markers in embryos in which VegT transcripts have been ablated but does not restore the ability of vegetal pole blastomeres to induce mesoderm. These results demonstrate that Bix4 acts directly downstream of VegT to specify endodermal differentiation in Xenopus embryos.

Animals↗
PubMed1999

Goosecoid and mix.1 repress Brachyury expression and are required for head formation in Xenopus.

The Xenopus homologue of Brachyury, Xbra, is expressed in the presumptive mesoderm of the early gastrula. Induction of Xbra in animal pole tissue by activin occurs only in a narrow window of activin concentrations; if the level of inducer is too high, or too low, the gene is not expressed. Previously, we have suggested that the suppression of Xbra by high concentrations of activin is due to the action of genes such as goosecoid and Mix.1. Here, we examine the roles played by goosecoid and Mix.1 during normal development, first in the control of Xbra expression and then in the formation of the mesendoderm. Consistent with the model outlined above, inhibition of the function of either gene product leads to transient ectopic expression of Xbra. Such embryos later develop dorsoanterior defects and, in the case of interference with Mix.1, additional defects in heart and gut formation. Goosecoid, a transcriptional repressor, appears to act directly on transcription of Xbra. In contrast, Mix.1, which functions as a transcriptional activator, may act on Xbra indirectly, in part through activation of goosecoid.

3T3 Cells↗
PubMed1999

Stress, relaxation states, and creativity.

114 participants in four groups practiced 25 minutes of progressive muscle relaxation, yoga stretching, imagery, or a control task. Before and after training, participants took state versions of the Smith Quick Stress Test (which measures Somatic Stress, Negative Affect, and Worry) and the Smith R-State Inventory (which measures relaxation-related states Disengagement, Physical Relaxation, Mental Relaxation, Strength and Awareness, Joy, Love and Thankfulness, and Prayerfulness). After training, all took both the Verbal and Figural forms of the Torrance Tests of Creative Thinking. At posttest, groups' scores did not differ on Creativity; however, when compared with yoga stretching, imagery trainees had lower posttest scores on Negative Affect. Both yoga stretching and imagery trainees displayed higher scores on self-reported Physical Relaxation than did controls. Progressive muscle relaxation trainees had lower scores on Somatic Stress than controls. Paradoxically, for all relaxation trainees, Disengagement (feeling "distant, far away, indifferent") correlated positively with both Negative Affect and Physical Relaxation, suggesting that disengagement in relaxation may not lead to relaxation-induced anxiety but may help one cope with such anxiety.

Adaptation, Psychological↗
PubMed1999

Antagonism of immunostimulatory CpG-oligodeoxynucleotides by 4-aminoquinolines and other weak bases: mechanistic studies.

Oligodeoxynucleotides with unmethylated CpG motifs are immunostimulatory. Chloroquine and a number of structural analogs specifically and powerfully inhibit this effect at nanomolar concentrations. We explored the mechanism of this inhibition, with 4-aminoquinolines, quinacrine, 9-aminoacridines, and novel dibasic analogs, many of which are fluorescent. WEHI 231 murine B-lymphoma cells accumulated analogs up to a concentration several hundredfold higher than the medium. Uptake was rapid, nonsaturable, reversible, and partially inhibited by monensin, an agent that collapses pH gradients within cells. Uptake did not correlate highly with efficacy as inhibitors of CpG-oligodeoxynucleotide (ODN)-induced effects, suggesting that analogs act by a specific action. Confocal microscopy revealed analogs concentrating in large peripheral organelles. CpG-ODN is taken up by cells into acidified, small, perinuclear vesicles. This uptake is thought to be necessary for immunostimulatory activity. Cellular uptake of fluorescent CpG-ODN was not inhibited by the analogs. The pH of intracellular CpG-ODN (6. 4) was not affected by analogs at the concentration required for inhibition, but pH was increased by higher concentrations. UV spectroscopy revealed no binding of analogs to CpG-ODN. Nuclear Overhauser effect spectroscopy revealed that an analog bound to phosphatidylcholine vesicles, with the ring structure of the analog buried within the lipid and the side chain facing the aqueous environment. We conclude that the analogs do not inhibit the action of CpG-ODN by preventing the uptake or acidification of CpG-ODN. It seems more likely that the analogs inhibit the efficacy of CpG-ODN by a specific action within acidified vesicles, possibly at the interface of a phospholipid membrane.

Adjuvants, Immunologic↗