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Biomedical subjects

Paul Gordon

Publications and source records attributed to Paul Gordon.

At least 19 recordsLinked to original sources
PubMed2006

The effect of apolipoprotein E genotype on serum lipoprotein particle response to exercise.

Exercise affects lipoprotein metabolism and apolipoprotein E (Apo E) genotype may alter changes in lipoprotein subclasses that occur with exercise. The present study examined the effects of Apo E genotype (APOE) on the response of lipoprotein subclass concentrations to long-term exercise. A prospective longitudinal study, conducted at seven centers, genetically screened 566 individuals to create three cohorts of healthy adults, equal for gender and the most common APOE variants: E2/3 (n = 35), E3/3 (n = 40), and E3/4 (n = 31). Subjects with body mass index (BMI) > or = 31 or evidence of dyslipidemia or metabolic disease were excluded. All subjects exercised aerobically at 75% of maximal heart rate for 40 min, four times weekly for 6 months. Fasting lipoprotein subpopulations were measured before and after exercise training using proton nuclear magnetic resonance spectroscopy. Serum lipids for the entire cohort did not change with exercise training, but the LDL subpopulation response varied by APOE. Small-sized LDL particles decreased only in the APOE3 homozygotes whereas medium-sized LDL particles increased only in this group. These changes were directionally different from the responses in the E2/3 and E3/4 subjects (p < 0.05). Neither exercise nor APOE variant affected overall LDL or HDL size or cholesterol concentration, but exercise decreased VLDL diameter by 3.5 nm (p < 0.001) attributable to decreases in large VLDL in each APOE group. In conclusion, APOE variants influence the serum LDL subpopulation response to exercise training in normolipidemic subjects. Subjects homozygous for APOE3 experienced the most beneficial lipid effects from exercise training.

Adolescent↗
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↗
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

Impact of moderate renal insufficiency on restenosis and adverse clinical events after paclitaxel-eluting and bare metal stent implantation: results from the TAXUS-IV Trial.

BACKGROUND: Mortality and restenosis may be increased in patients with mild to moderate renal insufficiency (RI) after coronary stent implantation. Whether drug-eluting stents safely reduce restenosis and enhance event-free survival in these patients is unknown. We sought to evaluate the impact of baseline RI on clinical and angiographic outcomes in patients undergoing elective percutaneous coronary intervention using either bare metal or paclitaxel-eluting stents. METHODS: In the TAXUS-IV trial, 1314 patients were randomized to either the polymer-based paclitaxel-eluting TAXUS stent or an identical-appearing bare metal stent. Outcomes were stratified on the basis of the presence of RI, defined as a baseline creatinine clearance < 60 cm3/min calculated by the Cockcroft-Gault formula. RESULTS: Baseline RI was present in 223 (17.2%) patients, in whom the mean creatinine clearance was 49.6 +/- 8.5 cm3/min. Compared with bare metal stents, treatment with the TAXUS stent resulted in lower rates of 9-month angiographic restenosis rates in both patients with (2.1% vs 20.5%, P = .009) and without (9.2% vs 27.8%, P < .0001) baseline RI. Similarly, 1-year target lesion revascularization rates were reduced with the TAXUS stent in patients with (3.3% vs 12.2%, P = .01) and without (4.7% vs 15.8%, P < .0001) baseline RI. The occurrence of death, myocardial infarction, and stent thrombosis at 1 year were similar in both randomization groups, independent of renal function. CONCLUSIONS: The polymer-based paclitaxel-eluting TAXUS stent safely reduces clinical and angiographic restenosis in patients with preserved as well as moderate impairment of baseline renal function.

Aged↗
PubMed2005

Nondisease genetic testing: reporting of muscle SNPs shows effects on self-concept and health orientation scales.

The purpose of this study was to assess the impact of genetic self-knowledge (nondisease genotype information) on individual self-concept and Health Orientation Scale (HOS). Adult volunteers (n=257) were recruited from an ongoing genetic association study identifying muscle quantitative trait loci (QTLs). Participants completed psychosocial assessments before and after 12 weeks of resistance training of the nondominant arm. At study exit, a genetic counselor informed participants of genetic test results on three to four genes that have an association with muscle-related traits, and counseled subjects on the potential significance of these findings. The second psychosocial assessment was performed immediately following this counseling session. The Tennessee Self-Concept Scale v.2 (TSCS:2) and the HOS showed female subjects to have a significantly greater positive change between first and second assessments, relative to male subjects. Most self-concept subscales improved significantly, when 'neutral' genotypes (no anticipated beneficial or deleterious impact) were reported, compared to positive genotypes. TSCS:2 subscales showing improvement included: total (P=0.013); physical (P=0.004); satisfaction (P=0.019); and behavioral (P=0.047). HOS subscales showing improvement included health image concern (P=0.006); and health expectations (P=0.047). In conclusion, these results suggest that genetic self-knowledge affects self-concept, consistent with the 'attribution' theory. Individuals who received neutral genetic information attributed positive changes from the exercise program to their own abilities, while those who received positive information were more likely to attribute positive changes to their genetics. This study is limited by the ability to determine the direction of the impact of nondisease genetic information presented to participants.

Adult↗
PubMed2004

Comparison of directional coronary atherectomy and stenting versus stenting alone for the treatment of de novo and restenotic coronary artery narrowing.

Late lumen loss after directional coronary atherectomy (DCA) is mainly determined by arterial remodeling. We hypothesized that stent implantation after optimal lesion debulking could be an effective approach to reduce restenosis. A total of 753 patients with de novo or restenotic coronary lesions were prospectively randomized to DCA plus stenting (n = 381) or stenting alone (n = 372). The patients were followed for 12 months. Procedural success was achieved in 91.5% versus 97.3% (p = 0.0007) of patients treated with DCA plus stent versus stent alone. Optimal atherectomy (<20% residual stenosis) was achieved in 26.5% of patients. The final minimal luminal diameter and the acute gain were similar in the 2 groups. There was no increase in 30-day major adverse cardiac events in the DCA plus stent group (3.9% vs 2.4%, p = 0.30). The primary end point, angiographic restenosis at 8 months, occurred in 26.7% of patients treated with DCA plus stents and in 22.1% of patients treated with stents alone (p = 0.237). Clinical follow-up to 1 year showed no difference in mortality (1.3% vs 0.8%, p = 0.725), acute myocardial infarction (4.2% vs 3.5%, p = 0.706), and target vessel failure (composite of death, Q-wave myocardial infarction, and target vessel revascularization) (23.9% vs 21.5%, p = 0.487) between patients with DCA plus stents and those with stents alone. This study failed to support the hypothesis that DCA before stenting lowers the angiographic restenosis rate compared with stents alone. At 12-month follow-up, there were no significant differences between the 2 groups in rates of death, reinfarction, or target vessel failure.

Adult↗
PubMed2004

Apolipoprotein E genotype and changes in serum lipids and maximal oxygen uptake with exercise training.

Physical activity improves lipid levels by altering triglyceride (TG) metabolism. Apolipoprotein E (Apo E) facilitates TG clearance by mediating lipoprotein binding to hepatic receptors, but Apo E also has less defined roles in skeletal muscle and nervous tissue. This study examined if variants in Apo E genotype affect the lipid and physiologic response to exercise training. Seven centers genetically screened 566 individuals to recruit 120 subjects into 6 gender-specific cohorts equal for the most common Apo E genotypes: E2/3, E3/3, and E3/4. Anthropometics, exercise capacity (Vo(2)max), serum lipids, and post heparin (PH) plasma lipase activities were measured before and after 6 months of supervised exercise training. Difference in the response (Delta) to training among the Apo E genotypes was the primary outcome variable. Differences in pretraining serum lipids among the Apo E genotypes mimicked those observed in population studies: TGs were slightly higher in E2/3 subjects, whereas low-density lipoprotein (LDL)-cholesterol (C) was lower (P = not significant [NS] ). TGs decreased 11% with training for the entire cohort (P <.0001) and 7%, 12%, and 14% for the Apo E 2/3, 3/3 and 3/4 groups, respectively (P = NS for Delta). LDL-C did not change in the entire cohort, but decreased slightly in the 2/3 and 3/3 subjects and increased 4% in the 3/4 group (P = NS for Delta). High-density lipoprotein (HDL)-C increased 2% for the entire cohort (P =.06) due to a 6% increase in the 3/3 group (P =.07 for Delta). Total cholesterol (TC)/HDL and LDL/HDL decreased with training in the 2/3 and 3/3 groups, but increased in the 3/4 subjects and these responses differed among the genotypes (P <.05 for Delta). Vo(2)max increased 9% to 10% for the entire cohort, but only 5% in the 3/3 subjects versus 13% in the 2/3 and 3/4 groups and these differences were significantly different among the genotypes (P <.01 for Delta). This is the first prospective study to demonstrate that the serum lipid response to exercise training differs by Apo E genotype in a pattern consistent with known metabolic differences among the variants. Surprisingly, Apo E genotype also affected the increase in aerobic capacity produced by exercise training possibly via undefined effects on nerve and skeletal muscle function.

Adult↗
PubMed2004

Reconstruction of the central carbohydrate metabolism of Thermoproteus tenax by use of genomic and biochemical data.

The hyperthermophilic, facultatively heterotrophic crenarchaeum Thermoproteus tenax was analyzed using a low-coverage shotgun-sequencing approach. A total of 1.81 Mbp (representing 98.5% of the total genome), with an average gap size of 100 bp and 5.3-fold coverage, are reported, giving insights into the genome of T. tenax. Genome analysis and biochemical studies enabled us to reconstruct its central carbohydrate metabolism. T. tenax uses a variant of the reversible Embden-Meyerhof-Parnas (EMP) pathway and two different variants of the Entner-Doudoroff (ED) pathway (a nonphosphorylative variant and a semiphosphorylative variant) for carbohydrate catabolism. For the EMP pathway some new, unexpected enzymes were identified. The semiphosphorylative ED pathway, hitherto supposed to be active only in halophiles, is found in T. tenax. No evidence for a functional pentose phosphate pathway, which is essential for the generation of pentoses and NADPH for anabolic purposes in bacteria and eucarya, is found in T. tenax. Most genes involved in the reversible citric acid cycle were identified, suggesting the presence of a functional oxidative cycle under heterotrophic growth conditions and a reductive cycle for CO2 fixation under autotrophic growth conditions. Almost all genes necessary for glycogen and trehalose metabolism were identified in the T. tenax genome.

Archaeal Proteins↗
PubMed2004

Functional polymorphisms associated with human muscle size and strength.

INTRODUCTION: Skeletal muscle is critically important to human performance and health, but little is known of the genetic factors influencing muscle size, strength, and its response to exercise training. The Functional single nucleotide polymorphisms (SNP) Associated with Muscle Size and Strength, or FAMuSS, Study is a multicenter, NIH-funded program to examine the influence of gene polymorphisms on skeletal muscle size and strength before and after resistance exercise training. METHODS: One thousand men and women, age 18 - 40 yr, will train their nondominant arm for 12 wk. Skeletal muscle size (magnetic resonance imaging) and isometric and dynamic strength will be measured before and after training. Individuals whose baseline values or response to training deviate > or = 1.5 SD will be defined as outliers and examined for genetic variants. Initially candidate genes previously associated with muscle performance will be examined, but the study will ultimately attempt to identify genes associated with muscle performance. CONCLUSION: FAMuSS should help identify genetic factors associated with muscle performance and the response to exercise training. Such insight should contribute to our ability to predict the individual response to exercise training but may also contribute to understanding better muscle physiology, to identifying individuals who are susceptible to muscle loss with environmental challenge, and to developing pharmacologic agents capable of preserving muscle size and function.

Adolescent↗
PubMed2004

ACGME Outcomes Project: selling our expertise.

The Accreditation Council for Graduate Medical Education (ACGME) Outcomes Project emphasizes competency outcome assessment by residency programs. Many residency programs are unprepared to undertake valid competency assessments. Family medicine educators, however, often have substantial experience in competency-based evaluation. We developed a program, with more than 240,000 US dollars of funding from our dean's office, through which our family medicine educational unit provided support to more than 60 residency programs in various specialties. This program assisted directors of these 60 programs to understand the ACGME competency domains, develop measurable competencies for their discipline, and develop evaluation tools to assess those competencies. We were thus able to "sell" our expertise to other programs and generate income for our department.

Competency-Based Education↗
PubMed2003

Megadose transplantation of highly purified haploidentical stem cells: current results and future prospects.

The transplantation of megadoses of haploidentical hematopoietic stem cells is for a number of children with malignant or nonmalignant diseases the only curative approach. In order to prevent severe GvHD, the removal of T lymphocytes from the stem cell graft either by positive selection of CD34+ stem cells or by negative depletion of CD3+ T lymphocytes is necessary. We present the results obtained so far by CD34+ positive selection and discuss new techniques of graft engineering which might hopefully further improve the outcome of haploidentical stem cell transplantation.

Antigens, CD34↗
PubMed2003

Cognitive behavioral stress management effects on injury and illness among competitive athletes: a randomized clinical trial.

Cognitive behavioral stress management (CBSM) has previously been found to reduce fatigue, depression, and cortisol response to heavy exercise training among competitive collegiate athletes and to speed physical and psychological recovery from surgery. Our study assessed the efficacy of a CBSM program to reduce the frequency of injury and illness among collegiate athletes in a randomized, single-blind, controlled clinical trial. Following assessment of baseline medical history, mood state, stress, cortisol, sleep, alcohol use, and exercise training, collegiate rowers were stratified by gender and competitive level and randomly assigned to either a control group or a CBSM group. Exercise training information and psychosocial assessments were repeated immediately following the intervention period, and health care providers who were blinded to participant assignment recorded the frequency of medical visits and the number of days injured or ill until the end of the season. Athletes randomly assigned to a CBSM group experienced significant reductions in the number of illness and injury days as compared to control group athletes. CBSM participants also had half the number of health service visits as did controls. The data suggest that a time-limited CBSM intervention designed specifically for an athlete population may be an effective prophylactic treatment to reduce the incidence of injury and illness among competitive collegiate athletes.

Adolescent↗
PubMed2003

ST-segment elevation myocardial infarction, severe anemia and nonobstructive coronary disease: case report and brief comment.

When the metabolic demand of the heart exceeds its oxygen supply, myocardial ischemia or infarction (MI) may occur. One of the causes of this condition is severe anemia. The type of MI associated with cases of supply-demand myocardial mismatch is usually a non-ST elevation infarction (Non-STEMI), and is most commonly seen in patients with underlying coronary artery disease. We present a case report of ST segment elevation MI (STEMI), which we believe was secondary to severe anemia, occurring in the absence of angiographically significant coronary artery stenosis or thrombosis. Coronary artery spasm was not seen. In our review of the literature we found no similar cases (MEDLINE 1966-2002).

Anemia↗
PubMed2002

The analysis of 100 genes supports the grouping of three highly divergent amoebae: Dictyostelium, Entamoeba, and Mastigamoeba.

The phylogenetic relationships of amoebae are poorly resolved. To address this difficult question, we have sequenced 1,280 expressed sequence tags from Mastigamoeba balamuthi and assembled a large data set containing 123 genes for representatives of three phenotypically highly divergent major amoeboid lineages: Pelobionta, Entamoebidae, and Mycetozoa. Phylogenetic reconstruction was performed on approximately 25,000 aa positions for 30 species by using maximum-likelihood approaches. All well-established eukaryotic groups were recovered with high statistical support, validating our approach. Interestingly, the three amoeboid lineages strongly clustered together in agreement with the Conosa hypothesis [as defined by T. Cavalier-Smith (1998) Biol. Rev. Cambridge Philos. Soc. 73, 203-266]. Two amitochondriate amoebae, the free-living Mastigamoeba and the human parasite Entamoeba, formed a significant sister group to the exclusion of the mycetozoan Dictyostelium. This result suggested that a part of the reductive process in the evolution of Entamoeba (e.g., loss of typical mitochondria) occurred in its free-living ancestors. Applying this inexpensive expressed sequence tag approach to many other lineages will surely improve our understanding of eukaryotic evolution.

Amoeba↗
PubMed2002

Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition.

The ability of the pathogenic fungus Candida albicans to switch from a yeast to a hyphal morphology in response to external signals is implicated in its pathogenicity. We used glass DNA microarrays to investigate the transcription profiles of 6333 predicted ORFs in cells undergoing this transition and their responses to changes in temperature and culture medium. We have identified several genes whose transcriptional profiles are similar to those of known virulence factors that are modulated by the switch to hyphal growth caused by addition of serum and a 37 degrees C growth temperature. Time course analysis of this transition identified transcripts that are induced before germ tube initiation and shut off later in the developmental process. A strain deleted for the Efg1p and Cph1p transcription factors is defective in hyphae formation, and its response to serum and increased temperature is almost identical to the response of a wild-type strain grown at 37 degrees C in the absence of serum. Thus Efg1p and Cph1p are needed for the activation of the transcriptional program that is induced by the presence of serum.

Candida albicans↗