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Biomedical subjects

Paul D Thompson

Publications and source records attributed to Paul D Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2006

Dose-dependent effects of training and detraining on weight in 6406 runners during 7.4 years.

OBJECTIVE: Prior randomized and non-randomized training studies have failed to establish a dose-response relationship between vigorous exercise and weight loss; this failure may be due, in part, to their short durations and small sample sizes. The objectives of this study were to determine whether exercise reduces body weight and to examine the dose-response relationships between changes in exercise and changes in total and regional adiposity. RESEARCH METHODS AND PROCEDURES: This was a large prospective study of 3973 men and 1444 women who quit running (detraining), 270 men and 146 women who started running (training), and 420 men and 153 women who remained sedentary during 7.4 years of follow-up. The outcomes measured were weekly running distance, body weight, BMI, body circumferences, and bra cup size. RESULTS: There were significant inverse relationships between the changes in the amount of vigorous exercise (km/wk run) and the changes in weight and BMI in men (slope +/- standard error: -0.039 +/- 0.005 kg/km per week and -0.012 +/- 0.002 kg/m(2) per km/wk, respectively) and in older women (-0.060 +/- 0.018 kg/km per week and -0.022 +/- 0.007 kg/m(2) per km/wk) who quit running, and in initially sedentary men (-0.098 +/- 0.017 kg/km per week and -0.032 +/- 0.005 kg/m(2) per km/wk) and women (-0.062 +/- 0.023 kg/km per week and -0.021 +/- 0.008 kg/m(2) per km/wk) who started running. Changes in waist circumference, an indicator of intra-abdominal fat, were also inversely related to changes in running distance in men who quit (-0.026 +/- 0.005 cm/km per week) or started running (-0.078 +/- 0.017 cm/km per week). DISCUSSION: The initiation of vigorous exercise and its cessation decrease and increase, respectively, body weight and intra-abdominal fat, and these changes are proportional to the change in exercise dose.

Adipose Tissue↗
PubMed2006

Angiotensin-converting enzyme genotype and adherence to aerobic exercise training.

Angiotensin-converting enzyme (ACE) has two common genetic variants: the insertion (I) and deletion (D) forms. ACE levels are greater in subjects with the D allele, and several studies suggest superior endurance performance in subjects with the I allele. The authors recently reported the results of a 6-month exercise training protocol examining the effect of apolipoprotein E on the lipid response. The present report examines the relationship of ACE genotype and exercise adherence. DNA samples were available for 110 subjects: 14 I/I, 52 I/D, and 44 D/D. Baseline and change in maximal oxygen uptake, body mass index, skinfold thickness, and serum lipids did not differ by ACE genotype, but adherence to exercise training was higher in I carriers than in D homozygotes. These preliminary results suggest that ACE genotype affects exercise adherence and raises the possibility that superior endurance capacity in subjects with the I allele is related to a genetic propensity to adhere to an exercise regimen.

Adolescent↗
PubMed2006

The acute effect of aerobic exercise on brachial artery endothelial function in renal transplant recipients.

This study compared the effect of a 30-minute walk on brachial artery endothelial vasodilatation in kidney transplant (KT) recipients and healthy controls (HCs). Endothelial-dependent vasodilatation was measured by ultrasound before and after exercise. The HCs experienced a significant increase in vasodilatation after exercise 1 minute postocclusion when compared with the KT recipients (22%+/-13% vs 3%+/-4%; P<.05). Also, the HCs had a significantly higher vasodilatation from pre-treadmill walk to post-treadmill walk (1 minute postocclusion) when compared with KT recipients (from 3%+/-6% to 22%+/-13% vs 1%+/-3% to 3%+/-4%; P<.05). This acute vasodilatory response observed in the HCs may be related to the immediate release of nitric oxide and the combined response to shear stress and exercise. The KT recipients had several coronary artery disease risk factors that may have adversely affected endothelial function.

Adult↗
PubMed2006

Serum creatine kinase levels and renal function measures in exertional muscle damage.

PURPOSE: Serum creatine kinase (CK) levels are commonly used to judge the severity of muscle damage and to determine when to hospitalize patients who present with symptoms of exertional rhabdomyolysis in order to prevent renal failure. However, no CK standard exists because of the limited information available regarding exercise-induced CK elevation and renal function. This study determined the magnitude of CK elevation and the effect on renal function produced by exercise in a large subject group. METHODS: Blood samples were obtained from 203 volunteers who performed 50 maximal eccentric contractions of the elbow flexor muscles. The samples, taken before and 4, 7, and 10 d after exercise, were analyzed for markers of muscle damage (CK, myoglobin (Mb), lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase and for measures of renal function (creatinine, blood urea nitrogen, phosphorus, potassium, osmolality, and uric acid). RESULTS: All indicators of muscle damage increased significantly after exercise (P < 0.01). CK levels were 6420, 2100, and 311% above baseline on days 4, 7, and 10 after the exercise, respectively (P < 0.01), and Mb was 1137, 170, and 28% above baseline on days 4, 7, and 10 after exercise, respectively (P < 0.01). Of the 203 participants, 111 had CK values at 4 d postexercise > 2,000 U x L(-1) and 51 had values > 10,000 U x L(-1), levels used to diagnose myopathy (e.g., statin myositis) and rhabdomyolysis, respectively. There were no significant increases in any measure of renal function. Despite marked CK and Mb elevations in some subjects, none experienced visible myoglobinuria or required treatment for impaired renal function. CONCLUSIONS: Exertional muscle damage produced by eccentric exercise in healthy individuals can cause profound CK and Mb elevations without renal impairment.

Adolescent↗
PubMed2006

The congenital long QT syndrome and implications for young athletes.

The congenital long QT syndrome (LQTS) is caused by cardiac ion channel mutations, which predispose young individuals to sudden cardiac death often related to exercise. The issue of LQTS and sports participation has received significant publicity due to reports of sudden death in young competitive athletes. This article reviews the pathophysiology, clinical characteristics, and management of LQTS in the physically active and athletic population.

Adolescent↗
PubMed2006

ACE ID genotype and the muscle strength and size response to unilateral resistance training.

PURPOSE: To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d.wk) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. METHODS: Subjects were 631 (mean+/-SEM, 24.2+/-0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (chi=1.688, P=0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. RESULTS: Baseline muscle strength and size were greater in UT than T (P<0.001) and did not differ among ACE ID genotype in either arm (P >or= 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P<0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P >or= 0.05). In UT, MVC increased among ACE II/ID (7%) (P<0.001) but was similar among ACE DD (2%) pre- to post-RT (P >or= 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P<0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P<0.05). CONCLUSION: ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.

Adult↗
PubMed2006

The genetics of left ventricular remodeling in competitive athletes.

Left ventricular (LV) remodeling in competitive athletes is a complex phenomenon, in which genetic and environmental determinants are implicated. In recent years, several investigations have demonstrated an association between LV remodeling and the angiotensin-converting enzyme (ACE I/D) and/or angiotensinogen (AGT M/T) polymorphism, with athletes with the DD and/or TT alleles, respectively, showing the greatest increase in LV mass, independent from other determinants. However, the impact of the known genetic determinants on LV remodeling is at present incomplete, and comparative assessment of the genetic and environmental factors, such as the type and intensity of athletic conditioning, suggests that genetic determinants may explain up to one-quarter of the overall variability of LV dimensions. A better understanding of genetic factors may provide an insight into the pathways producing physiological cardiac remodeling, and will be important in understanding the intrinsic nature and clinical significance of the extreme LV morphologic changes observed in highly trained and elite athletes.

Exercise↗
PubMed2005

Phytosterols and vascular disease.

Phytosterols or plant sterols have long been known to lower serum cholesterol concentrations by competing with dietary and biliary cholesterol for intestinal absorption. Food products containing phytosterols and phytostanols are now available to assist in lowering blood cholesterol levels. In contrast to these possibly beneficial effects of plant sterols, a rare genetic condition called sitosterolemia, an autosomal recessive disorder also known as phytosterolemia, is characterized by over absorption of phytosterols and premature coronary artery and aortic valve disease. Phytosterols have also recently been identified in atheromatous plaque obtained from individuals with apparently normal absorption of plant sterols raising the possibility that phytosterols are a novel atherosclerotic risk factor. This article reviews phytosterols and their relationship to vascular disease.

Absorption↗
PubMed2005

Changes in ubiquitin proteasome pathway gene expression in skeletal muscle with exercise and statins.

OBJECTIVE: Statins are safe medications but have side effects including myalgia and rhabdomyolysis. How statins provoke muscle damage is not known, but this effect is exacerbated by exercise. METHODS AND RESULTS: Healthy subjects took Atorvastatin (80 mg/daily) or placebo for 4 weeks. Biopsies of both vastus lateralis muscles were performed 8 hours after eccentric exercise (known to result in muscle soreness and damage) of the left leg at baseline and the right leg after statin/placebo treatment. Gene expression was determined using Affymetrix GeneChips, and selected genes confirmed by polymerase chain reaction (qRT-PCR). Atorvastatin had little effect on gene expression at rest. When combined with exercise, 56 genes were differentially expressed with 18% involved in the ubiquitin proteasome pathway (UPP) and 20% involved in protein folding and catabolism, and apoptosis. CONCLUSIONS: This is the first investigation to our knowledge to implicate involvement of the UPP in skeletal muscle in response to combined exercise and statin treatment, possibly explaining the onset of myalgia with exertion. Statins may alter the response of muscle to exercise stress by altering the action of the UPP, protein folding, and catabolism, disrupting the balance between protein degradation and repair.

Adolescent↗
PubMed2005

Apolipoprotein A1 genotype affects the change in high density lipoprotein cholesterol subfractions with exercise training.

High density lipoprotein cholesterol (HDL-C) is a primary risk factor for cardiovascular disease. Apolipoprotein A-1 (apoA1) is the major HDL-associated apolipoprotein. The -75G/A single nucleotide polymorphism (SNP) in the apolipoprotein A1 gene (APOA1) promoter has been reported to be associated with HDL-C concentrations as well as HDL-C response to dietary changes in polyunsaturated fat intake. We examined the effect of this APOA1 SNP on exercise-induced changes in HDL subfraction distribution. From a cohort of healthy normolipidemic adults who volunteered for 6 months of supervised aerobic exercise, 75 subjects were genotyped for the -75G/A SNP. Of these, 53 subjects were G homozygotes (G/G) and 22 were A carriers (A/G and A/A). HDL subfractions were measured by nuclear magnetic resonance (NMR) spectroscopy by adding categories HDL-C 1+2 for the small subfraction, and HDL-C 3+4+5 for the large. The change in total HDL-C after exercise was 0.8+/-7.2 mg/dL (+1.7%), and was not statistically significant. HDL subfraction amounts also did not significantly change with exercise training in the total cohort or in G homozygotes or A carriers. The amount of the large HDL subfraction increased in the G homozygotes and decreased in the A carriers (mean+/-S.E.M., 1.8+/-6.6 mg/dL versus -6.1+/-2.3 mg/dL, p<0.0005). In contrast, the amount of the small HDL subfraction decreased in G homozygotes and increased in A carriers (-1.3+/-6.6 mg/dL versus 4.7+/-1.2 mg/dL, p<0.005). These results show that genetic variation at the APOA1 gene promoter is associated with HDL subfraction redistribution resulting from exercise training.

Adolescent↗
PubMed2005

Prevention of coronary artery disease in cancer patients.

Improvements in cancer treatment are increasing survival rates, placing cancer survivors at increased risk of coronary artery disease (CAD). Thoracic radiation as cancer therapy can accelerate the atherosclerotic process, and some older studies suggest that mediastinal radiation can increase the CAD risk two to fivefold. The management of serum lipids using diet and drugs is the cornerstone of efforts designed to reduce CAD events. The present article reviews the association between radiation and coronary disease and provides guidelines for the prevention of atherosclerotic CAD in this patient group and in the general population of cancer survivors.

Antineoplastic Agents↗
PubMed2005

The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review.

Physical activity is associated with a reduced incidence of coronary disease, but the mechanisms mediating this effect are not defined. There has been considerable recent interest in inflammation in the pathogenesis of cardiovascular disease. Some of the beneficial role of physical activity may result from its effects on the inflammatory process. We searched PubMed for articles published between 1975 through May 2004 using the terms exercise, physical activity, or physical fitness combined with C-reactive protein, inflammation, inflammatory markers, or cytokines. The review revealed 19 articles on the acute inflammatory response to exercise, 18 on cross-sectional comparisons of subjects by activity levels, and 5 examining prospectively the effects of exercise training on the inflammatory process. Exercise produces a short-term, inflammatory response, whereas both cross-sectional comparisons and longitudinal exercise training studies demonstrate a long-term "anti-inflammatory" effect. This anti-inflammatory response may contribute to the beneficial effects of habitual physical activity.

C-Reactive Protein↗
PubMed2005

Molecular and functional comparison of 1,25-dihydroxyvitamin D(3) and the novel vitamin D receptor ligand, lithocholic acid, in activating transcription of cytochrome P450 3A4.

The vitamin D receptor (VDR) binds to and mediates the effects of the 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) hormone to alter gene transcription. A newly recognized VDR ligand is the carcinogenic bile acid, lithocholic acid (LCA). We demonstrate that, in HT-29 colon cancer cells, both LCA and 1,25(OH)(2)D(3) induce expression of cytochrome P450 3A4 (CYP3A4), an enzyme involved in cellular detoxification. We also show that LCA-VDR stimulates transcription of gene reporter constructs containing DR3 and ER6 vitamin D responsive elements (VDREs) from the human CYP3A4 gene. Utilizing gel mobility shift, pulldown, and mammalian two-hybrid assays, we observe that: (i) 1,25(OH)(2)D(3) enhances retinoid X receptor (RXR) heterodimerization with VDR more effectively than LCA, (ii) the 1,25(OH)(2)D(3)-liganded VDR-RXR heterodimer recruits full-length SRC-1 coactivator, whereas this interaction is minimal with LCA unless LXXLL-containing fragments of SRC-1 are employed, and (iii) both 1,25(OH)(2)D(3) and LCA enhance the binding of VDR to DRIP205/mediator, but unlike 1,25(OH)(2)D(3)-VDR, LCA-VDR does not interact detectably with NCoA-62 or TRIP1/SUG1, suggesting a different pattern of LCA-VDR comodulator association. Finally, residues in the human VDR (hVDR) ligand binding domain (LBD) were altered to create mutants unresponsive to 1,25(OH)(2)D(3)- and/or LCA-stimulated transactivation, identifying S237 and S225/S278 as critical for 1,25(OH)(2)D(3) and LCA action, respectively. Therefore, these two VDR ligands contact distinct residues in the binding pocket, perhaps generating unique receptor conformations that determine the degree of RXR and comodulator binding. We propose that VDR is a bifunctional regulator, with the 1,25(OH)(2)D(3)-liganded conformation facilitating high affinity endocrine actions, and the LCA-liganded configuration mediating local, lower affinity cellular detoxification by upregulation of CYP3A4 in the colon.

Base Sequence↗
PubMed2005

ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women.

The alpha-actinin 3 (ACTN3) gene encodes a protein of the Z disk of myofibers, and a polymorphism of ACTN3 results in complete loss of the protein. The ACTN3 genotype (R577X) has been found to be associated with performance in Australian elite athletes (Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, and North K. Am J Hum Genet 73: 627-631, 2003). We studied associations between ACTN3 genotype and muscle size [cross-sectional area of the biceps brachii via magnetic resonance imaging (MRI)] and elbow flexor isometric (MVC) and dynamic [1-repetition maximum (1-RM)] strength in a large group of men (N = 247) and women (N = 355) enrolled in a 12-wk standardized elbow flexor/extensor resistance training program of the nondominant arm at one of eight study centers. We found no association between ACTN3 R577X genotype and muscle phenotype in men. However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age. Women homozygous for the mutant allele (577X) demonstrated greater absolute and relative 1-RM gains compared with the homozygous wild type (RR) after resistance training when adjusted for body mass and age (P < 0.05). There was a trend for a dose-response with genotype such that gains were greatest for XX and least for RR. Significant associations were validated in at least one ethnic subpopulation (Caucasians, Asians) and were independent of training volume. About 2% of baseline MVC and of 1-RM strength gain after training were attributable to ACTN3 genotype (likelihood-ratio test P value, P = 0.01), suggesting that ACTN3 is one of many genes contributing to genetic variation in muscle performance and adaptation to exercise.

Actinin↗