Browsing by Author "Myers, Jonathan B."

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    Adaptation of the Slow Component of VO₂ Following 6 wk of High or Low Intensity Exercise Training
    Ocel, Jeffrey Vincent Jr. (Virginia Tech, 1997-10-30)
    Eighteen untrained males [age: 23 +/- 0.6 yr (SEM)] were randomized into high intensity (HIT: above lactate threshold, LT), moderate intensity (LIT: below the LT) or no training (NT) groups. Subjects trained on a cycle ergometer 4 days.wk-1 for 6 wk with the power output held constant. Maximal cycle ergometry was performed before and after the training period to determine changes in power output and oxygen consumption (VO2) at the LT and peak exertion. Before training and after 1, 2, 4, and 6 wk, subjects performed high constant-load (HCL) cycling bouts to quantify training adaptations in the SC. Training was designed to keep total work equivalent between the HIT and LIT groups. Increases in power output and VO2 at LT and peak exercise after 6 wk were noted in the HIT and LIT groups in comparison to NT group (p<0.05). No differences were noted between HIT and LIT. Two-way repeated measures ANOVA revealed a significant trial*group interaction for adaptation in the SC (p<0.001). After 1wk of training, a significant reduction in the SC was noted for HIT [mean+/-SEM]: (pre-training (PT): 703 +/- 61 ml.min-1; 1 wk: 396 +/- 60 ml.min-1) (- 44% from PT). Further adaptation for the HIT was also noted at 4 wk: 202 +/- 45 ml.min-1 (-71% from PT). For LIT, a significant reduction was noted at 2 wk (PT: 588+/-76 ml.min-1; 2 wk: 374 +/- 50ml.min-1) (-36% from PT). Further adaptation for LIT group was noted at 6 wk (252 +/- 38 ml.min-1) (- 57% from PT). Adaptation in SC was not noted at any interval for NT. Temporal changes in blood lactate (r = 0.40) and ventilation (r = 0.72) were significantly correlated with the changes for SC over the 6 wk training period (p<0.05). In conclusion, it was demonstrated that training at supra-LT and sub-LT intensities produces similar improvement in VO2 and power output at peak exercise and in the LT, when total work output is controlled. However, training at supra-LT intensity promotes larger and faster adaptations in the SC than training at the sub-LT levels.
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    Chronic Hypoxia and Cardiovascular Dysfunction in Sleep Apnea Syndrome
    Chittenden, Thomas William (Virginia Tech, 2002-07-24)
    The purpose of the current study was to test the hypothesis that chronic hypoxia associated with sleep-disordered breathing relates to abnormal Nitric Oxide (NO) production and vascular endothelial growth factor (VEGF) expression patterns that contribute to aberrancy of specific determinates of cardiovascular and cardiopulmonary function before, during, and after graded exercise. These patterns may further reflect pathologic alteration of signaling within the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt-1) transduction network. To this end, 7 medically diagnosed OSA patients (3 male, 4 female), mean age 48 years and 7 apparently healthy control subjects (3 male, 4 female), mean age 42 years, underwent baseline venous blood draws and maximal bicycle ergometry. Mononuclear cells isolated from peripheral blood were utilized as reporter cells for measurement of VEGF, Akt-1, hypoxia inducible factor-1 alpha (HIF-1 alpha), and vascular endothelial growth factor receptor-2 (VEGFR2) gene expression by redundant oligonucleotide DNA microarray and real-time PCR technologies. Circulating angiogenic progenitor cells expressing VEGFR2 were profiled by flow cytometry. Plasma and serum concentrations of VEGF, nitrates/nitrites, catecholamines, and dopamine were measured by enzyme-linked immunosorbent assay (ELISA) and high performance liquid chromatography (HPLC). Arterial blood pressure, cardiac output, oxygen consumption and total peripheral resistance were determined at Baseline, 100W, and peak ergometric stress by standard techniques. There were no apparent differences (p < .05) observed in biochemical markers relating to vascular function and adaptation including, serum nitrates/nitrites, norepinephrine, dopamine, and plasma VEGF. No differences were found relative to cardiac output, stroke volume, cardiopulmonary or myocardial oxygen consumption, expired ventilation, heart rate, arteriovenous oxygen difference, total peripheral resistance, and mean arterial pressure. Due to methodological issues related to the redundant oligonucleotide DNA microarray and real-time PCR gene expression analyses, results of these experiments were uninterpretable. Thus, the research hypothesis was rejected. Conversely, significant (p < .05) differences were observed in waist: hip ratios, recovery: peak systolic blood pressure ratio at 1 minute post-exercise and %VEGFR2 expression. OSA was associated with elevations in both waist: hip ratios and recovery: peak systolic blood pressure ratio at 1 minute post-exercise as well as significant depression of %VEGFR2 profiles. Moreover, significant negative correlations were found regarding waist: hip ratios and %VEGFR2 expression (r = -.69;p =.005) and recovery: peak systolic blood pressure ratio at 1 minute post-exercise and %VEGFR2 expression (r = -.65;p =.01). These findings did not provide evidence that NO-dependent vasoactive mechanisms are suppressed nor did they support the supposition that angiogenic mechanisms are pathologically activated in sleep-disordered breathing.
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    H++: a server for estimating pK(a)s and adding missing hydrogens to macromolecules
    Gordon, John C.; Myers, Jonathan B.; Folta, Timothy; Shoja, Valia; Heath, Lenwood S.; Onufriev, Alexey V. (2005-07-01)
    The structure and function of macromolecules depend critically on the ionization (protonation) states of their acidic and basic groups. A number of existing practical methods predict protonation equilibrium pK constants of macromolecules based upon their atomic resolution Protein Data Bank (PDB) structures; the calculations are often performed within the framework of the continuum electrostatics model. Unfortunately, these methodologies are complex, involve multiple steps and require considerable investment of effort. Our web server http://biophysics.cs.vt.edu/H++ provides access to a tool that automates this process, allowing both experts and novices to quickly obtain estimates of pKs as well as other related characteristics of biomolecules such as isoelectric points, titration curves and energies of protonation microstates. Protons are added to the input structure according to the calculated ionization states of its titratable groups at the user-specified pH; the output is in the PQR (PDB + charges + radii) format. In addition, corresponding coordinate and topology files are generated in the format supported by the molecular modeling package AMBER. The server is intended for a broad community of biochemists, molecular modelers, structural biologists and drug designers; it can also be used as an educational tool in biochemistry courses.
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    Obstructive Sleep Apnea Risk in Abdominal Aortic Aneurysm Disease Patients: Associations with Physical Activity Status, Metabolic Syndrome, and Exercise Tolerance
    Mabry, J. Erin (Virginia Tech, 2013-05-03)
    Obstructive sleep apnea (OSA) is common in older U.S. adults and the prevalence is anticipated to rise in this age group along with obesity, a prominent risk factor for OSA. Recently, OSA was determined to be highly prevalent among patients with abdominal aortic aneurysm (AAA) disease. Objectives: Examine associations between OSA risk and physical activity (PA), metabolic syndrome (MetSyn), and exercise responses to cardiopulmonary exercise testing (CPET) in elderly patients with AAA disease. Methods: Elderly patients (n=326 for Studies 1 and 2; n=114 for Study 3) newly diagnosed with small AAAs (aortic diameter "2.5 and < 5.5 cm) were recruited. Data collection for all participants included: extraction of medical history and drug information from medical records; completion of a physical examination to assess resting vital signs and anthropometrics; fasting blood draw for several biochemical analyses; completion of a cardiopulmonary exercise test (CPET); and completion of interviews and questionnaires for health history, PA, and OSA risk. Results: 57% of subjects were High-risk for OSA and 17% were classified in the highest-risk Berlin Risk Score (BRS) 3 group; these subjects reported fewer blocks walked/day, flights of stairs climbed/day, and expended fewer Calories when engaged in these activities compared to Low-risk counterparts, independent of obesity. Among those at High-risk for OSA, 45% had MetSyn. Subjects with the highest BRS also had the highest prevalence of MetSyn and values for the MetSyn component biomarkers. Exercise capacity and physiological responses at rest, during exercise, and recovery were similar between groups at High- and Low-risk for OSA. Conclusions: Reduced levels of PA among elderly AAA patients at High-risk for OSA could have unfavorable implications for cardiovascular disease (CVD) risk and all-cause and CVD mortality.  Subjects demonstrating the most clinical symptoms of OSA showed a significantly higher prevalence for MetSyn and several of the biomarkers that determine MetSyn. In clinical practice, the BRS may be useful for identifying those AAA patients at increased risk for both OSA and MetSyn.