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Biomedical subjects

M F Carey

Publications and source records attributed to M F Carey.

At least 19 recordsLinked to original sources
PubMed1999

A mathematical model for synergistic eukaryotic gene activation.

The precise biochemical mechanism underlying the synergistic action of gene activators on eukaryotic transcription has eluded a solution, largely because of the technical difficulties inherent in analyzing the mechanics of a 2.5 MDa complex comprising greater than 50 polypeptide components. To complement the biochemical approach we have employed mathematical modeling as a means to understand the mechanism of synergy. Parameters relevant to activated transcription were varied in a simple biochemical system and the data were compared to the transcriptional response predicted by a multi-component statistical model. We found that the model achieved a consistent, semi-quantitative description of the measured transcriptional response, and enabled the characterization and measurement of thermodynamic parameters in the in vitro system. The results provide evidence for the existence of cooperativity in the activation process beyond what would be predicted from one current model suggesting that activators function solely by simple recruitment of the general transcription machinery to the promoter.

Binding Sites↗
PubMed1999

The effects of strength training on endurance performance and muscle characteristics.

PURPOSE: The purpose of this study was to determine the effects of resistance training on endurance performance and selected muscle characteristics of female cyclists. METHODS: Twenty-one endurance-trained, female cyclists, aged 18-42 yr, were randomly assigned to either a resistance training (RT; N = 14) or a control group (CON; N = 7). Resistance training (2X x wk(-1)) consisted of five sets to failure (2-8 RM) of parallel squats for 12 wk. Before and immediately after the resistance-training period, all subjects completed an incremental cycle test to allow determination of both their lactate threshold (LT) and peak oxygen consumption VO2). In addition, endurance performance was assessed by average power output during a 1-h cycle test (OHT), and leg strength was measured by recording the subject's one repetition maximum (1 RM) concentric squat. Before and after the 12-wk training program, resting muscle was sampled by needle biopsy from m. vastus lateralis and analyzed for fiber type diameter, fiber type percentage, and the activities of 2-oxoglutarate dehydrogenase and phosphofructokinase. RESULTS: After the resistance training program, there was a significant increase in 1 RM concentric squat strength for RT (35.9%) but not for CON (3.7%) (P < 0.05). However, there were no significant changes in OHT performance, LT, VO2, muscle fiber characteristics, or enzyme activities in either group (P > 0.05). CONCLUSION: The present data suggest that increased leg strength does not improve cycle endurance performance in endurance-trained, female cyclists.

Adolescent↗
PubMed1999

Muscle IMP accumulation during fatiguing submaximal exercise in endurance trained and untrained men.

To examine the effect of training status on muscle metabolism during exercise, seven endurance-trained [peak oxygen uptake (VO(2 peak)) = 65.8 +/- 2.4 ml. kg(-1). min(-1)] and six untrained (VO(2 peak) = 46. 2 +/- 1.9 ml. kg(-1). min(-1)) men cycled to fatigue at a work rate calculated to require 70% VO(2 peak). Time to exhaustion was 36% longer (P < 0.01) in trained (TR) compared with untrained (UT) men (148 +/- 11 vs. 95 +/- 8 min). Although intramuscular glycogen content was reduced (P < 0.05) in both TR and UT at fatigue, IMP, a marker of a mismatch between ATP supply and demand, was only elevated (P < 0.01) in UT muscle at fatigue and was approximately fourfold higher at this point in UT compared with TR. These data demonstrate that fatiguing submaximal exercise was associated with a similar low level of intramuscular glycogen in both TR and UT men, but a mismatch between ATP supply and demand only occurred in UT individuals.

Adult↗
PubMed1999

Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise.

To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3 degrees C (CT), 20 degrees C (NT), and 40 degrees C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher (P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 +/- 8 vs. 60 +/- 11 vs. 30 +/- 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher (P < 0.05) when HT was compared with NT, which in turn was higher (P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 +/- 33 vs. 153 +/- 27 and 116 +/- 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher (P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase (P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.

Adult↗
PubMed1999

Skeletal muscle oxidative capacity, fiber type, and metabolites after lung transplantation.

Lung transplant (LTx) recipients have a low peak work rate, peak oxygen consumption (V O2peak), and early lactate threshold on incremental exercise. We hypothesized that LTx recipients have reduced oxidative function and altered fiber type proportion in peripheral skeletal muscle. Seven stable LTx recipients and seven age- and sex-matched control subjects were studied. Incremental exercise testing with arterialized venous sampling and a resting quadriceps femoris punch muscle biopsy were performed. Muscle specimens were analyzed for fiber type proportion, metabolites, oxidative and glycolytic enzyme activities, and mitochondrial ATP production rate (MAPR) using standard techniques. The results showed that mean V O2peak in LTx recipients was 52% of control subjects. Compared with the control subjects, LTx skeletal muscle exhibited: (1) a lower MAPR; (2) lower activity of the mitochondrial enzymes glutamate dehydrogenase (GDH), citrate synthase (CS), 2-oxogluterate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA-dehydrogenase (HAD). There was no difference in the activities of anaerobic enzymes, except for higher phosphofructokinase activity; (3) a lower proportion of type I fibers; (4) a higher lactate and inosine monophosphate (IMP) content and a lower ATP content at rest indicating a high reliance on anaerobic metabolism. The reduced type I fiber proportion and severely reduced mitochondrial oxidative capacity may play an important role in exercise limitation after LTx.

Adult↗
PubMed1998

Effects of muscle fatigue and temperature on electromechanical delay.

The effect of repeated maximal isometric knee extensions on electromechanical delay (EMD) and associated muscle temperature changes were investigated on seven college aged subjects. The exercise produced a significant reduction in muscle contraction force, rate of force development and muscle conduction velocity, whilst the muscle temperature increased by 2.1 degrees C. The EMD increased from a pre-exercise value of 38.4 (SEM 3.4) ms to 55.7 (SEM 3.4) ms post-exercise. In an attempt to evaluate the effect of muscle temperature on EMD, hot and ice-water bags were placed on the quadriceps muscle to alter muscle temperature. The EMD in isometric maximal knee extension was measured at 38, 36, 34, 32 and 30 degrees C. The results showed that the EMD elongated at muscle temperatures either lower or higher than 36 degrees C. It was speculated that the increased muscle temperature might contribute to 20-25% of the EMD elongation found during the fatiguing intermittent exercise. The information of the effects of muscle temperature on EMD could be useful when evaluating the effects of strenuous exercise, in which a substantial muscle temperature change might occur, on the time delay between myoelectrical activity and force generation.

Adult↗
PubMed1997

Effect of muscle glycogen availability on maximal exercise performance.

This investigation determined the influence of pre-exercise muscle glycogen availability on performance during high intensity exercise. Nine trained male cyclists were studied during 75 s of all-out exercise on an air-braked cycle ergometer following muscle glycogen-lowering exercise and consumption of diets (energy content approximately 14 MJ) that were either high (HCHO(80% CHO) or low (LCHO-25% CHO) in carbohydrate content. The exercise-diet regimen was successful in producing differences in pre-exercise muscle glycogen contents [HCHO: 578(SEM 55) mmol x kg(-1) dry mass; LCHO: 364 (SEM 58) P < 0.05 mmol x kg(-1) dry mass]. Despite this difference in muscle glycogen availability, there were no between trial differences for peak power [HCHO 1185 (SEM 50)W, LCHO 1179 (SEM 48)W], mean power [HCHO 547 (SEM 5)W, LCHO 554 (SEM 8)W] and maximal accumulated oxygen deficit [HCHO 54.4 (SEM 2.3) ml x kg(-1), LCHO 54.6 (SEM 2.0) ml x kg(-1)]. Postexercise muscle lactate contents (HCHO 95.9 (SEM 4.6) mmol x kg(-1) dry mass, LCHO 82.7 (SEM 12.3) mmol x kg(-1) dry mass, n = 8] were no different between the two trials, nor were venous blood lactate concentrations immediately after and during recovery from exercise. These results would indicate that increased muscle glycogen availability has no direct effect on performance during all-out high intensity exercise.

Adult↗
PubMed1997

Muscle glycogen storage following prolonged exercise: effect of timing of ingestion of high glycemic index food.

This study examined the effect of delaying the ingestion of carbohydrate on muscle glycogen storage following prolonged exhaustive exercise. Six endurance trained men cycled on two separate occasions at a workload corresponding to 70% VO2max for 2 h followed by four "all-out" 30-s sprints. Following exercise, subjects were fed five high glycemic index (HGI) meals over a 24-h period, with the first three being fed either at 0-4 h (IT) or 2-6 h (DT) at 2-h intervals. Muscle biopsies were taken immediately after exercise and at 8 and 24 h post-exercise and analyzed for glycogen and glucose-6-phosphate. Blood samples were obtained prior to and at 30, 60, and 90 min after each meal and analyzed for glucose and insulin. No differences were observed in the incremental glucose and insulin areas after each meal when IT and DT were compared. In addition, no differences were observed in muscle glycogen or glucose-6-phosphate any time in the two trials. These data indicate that delayed feeding of a HGI meal by 2 h has no effect on the rate of muscle glycogen resynthesis at 8 and 24 h post-exercise, providing that sufficient carbohydrate is ingested during the recovery period.

Adult↗
PubMed1997

Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm.

The effects of almitrine bimesylate and doxapram HCl on isometric force produced by in vitro rat diaphragm were studied during direct muscle activation at 37 degrees C. Doxapram and almitrine ameliorate respiratory failure clinically by indirectly increasing phrenic nerve activity. This study was carried out to investigate possible direct actions of these agents on the diaphragm before and after fatigue of the fibers. Two age groups of animals were chosen [6-14 wk (group 1) and 50-55 wk (group 2)] because it is known that increasing age decreases a muscle fiber's resistance to fatigue. Muscle strips were isolated from both group 1 and group 2 and directly stimulated (2-ms pulse duration, 5-15 V) to produce twitch tensions of 1.3 and 2.1 N/cm2, respectively. At low concentrations, doxapram (</=20 microg/ml) and almitrine (</=12 microg/ml) had no effect on twitch contraction or 100-Hz tetanic tension. However, 40 microg/ml doxapram and 30 microg/ml almitrine increased twitch tension by 9.0 +/- 1.4 and 11.6 +/- 1.9%, respectively, in animals of group 2 (n = 5). A fatigue protocol consisting of low-frequency stimulation (30-Hz trains, 250-ms duration every 2 s for 5 min) caused a reduction of twitch tension in animals of group 1 (48 +/- 4% of control) and group 2 (28 +/- 4% of control). At 90 min postfatigue, the twitch tension recovered to 72 +/- 3 and 42 +/- 2% of control values in group 1 and group 2, respectively. In the presence of doxapram (20 microg/ml), there was a significant increase in the recovery of twitch tension at 90 min in group 1 and group 2 (84.5 +/- 3.2 and 80.1 +/- 2.8%, respectively) compared with controls at 90 min postfatigue. In the presence of almitrine (12 microg/ml), there was a full recovery from fatigue in group 1 animals (100% of control) and a recovery to 95.6 +/- 2.1% of control in group 2 animals at 90 min. These results demonstrate a significant improvement in the rapidity and magnitude of recovery from fatigue in the rat diaphragm muscle in the presence of both doxapram and, especially, almitrine. These effects may be due to changes in intracellular calcium, ADP/ATP ratios, or oxygen free radical scavenging.

Almitrine↗
PubMed1996

Anaerobic ATP production and accumulated O2 deficit in cyclists.

Anaerobic ATP production in skeletal muscle and the accumulated oxygen deficit (O2D) incurred during an exhaustive cycle bout (duration = 173 +/- 24 s; intensity = 112 +/- 3% VO2peak), were determined in 10 male cyclists (mean +/- SD: VO2peak = 69.8 +/- 4.2 ml.kg-1.min-1). Anaerobic ATP production (mmol.kg-1 d.w.) was determined from changes in lactate, phosphocreatine, ATP, and ADP in vastus lateralis. Muscle buffer value and the activities of glycogen phosphorylase (PHOS), phosphofructokinase and citrate synthase (CS) were also determined. The anaerobic ATP production determined from measured muscle metabolites was 202.7 +/- 46.9 mmol.kg-1 d.w. and was correlated (P < or = 0.05) with muscle buffer value (r = 0.81), PHOS (r = 0.69) and the ratio of PHOS to CS activity (r = 0.77). The O2D was 55.2 +/- 10.3 ml O2 Eq.kg-1, but was not correlated (P > 0.05) with anaerobic ATP production (r = -0.38), buffer value (r = -0.50) or PHOS (r = -0.39). These latter findings could be explained by error in measuring the O2D and/or muscle anaerobic ATP production in well-trained cyclists.

Adenosine Triphosphate↗
PubMed1996

Effect of CHO ingestion on exercise metabolism and performance in different ambient temperatures.

Two series of experiments were conducted to examine the effect of ingesting beverages with differing carbohydrate (CHO) concentrations and osmolalities on metabolism and performance during prolonged exercise in different environmental conditions. In series 1, 12 subjects performed three cycling exercise trials to fatigue at 70% VO2peak in either 33 degrees C (N = 6) (HT1) or 5 degrees C (N = 6) (CT). Subjects ingested either a 14% CHO solution (osmolality = 390 mosmol.1(-1) (HCHO); a 7% CHO solution (330 mosmol.1(-1) (NCHO) or a placebo (90 mosmol.1(-1) (CON1). In series 2, six subjects performed the same three trials at 33 degrees C (HT2), while ingesting either NCHO, a 4.2% CHO solution (240 mosmol.1(-1) (LCHO) or a placebo) (240 mosmol.1(-1) (CON2). Plasma glucose was higher (P < 0.05) in HCHO than NCHO, which in turn was higher (P < 0.05) than CON1 in both CT and HT1. Plasma glucose was lower (P < 0.05) in CON2 compared with NCHO and LCHO in HT2. The fall in plasma volume was greater (P < 0.05) in HCHO than other trials in both CT and HT1 but was not different when comparing the three trials in HT2. Exercise time was not different when comparing the trials in either HT1 or HT2 but was longer (P < 0.05) in NCHO compared with HCHO, which, in turn, was longer (P < 0.05) than CON1 in CT. These data demonstrate that, during prolonged exercise in the heat, fatigue is related to factors other than CHO availability. In addition, during exercise in 5 degrees C a 7% CHO solution is more beneficial for exercise performance than a 14% CHO solution.

Adult↗
PubMed1996

Blunting the rise in body temperature reduces muscle glycogenolysis during exercise in humans.

To examine the effect of blunting the rise in body temperature on exercise metabolism, seven endurance-trained men cycled for 40 min at 65% of maximal oxygen consumption (VO2,max) in an environmental chamber at either 20 degrees C and 20% relative humidity (RH) (T20) or 3 degrees C and approximately 50% RH (T3). The trials were conducted in random order at least 1 week apart. Mean oxygen consumption (VO2) during exercise was not different when comparing the two trials. In contrast, the mean respiratory exchange ratio (RER) was lower (P < 0.05) at T20 compared with T3. Heart rate, rectal temperature and plasma catecholamines were higher (P < 0.05) during exercise at T20 compared with T3, as was post-exercise muscle temperature (P < 0.01). Muscle and blood lactate and blood glucose concentrations were not significantly different when comparing T20 with T3. Net muscle glycogen utilization was greater (P < 0.05) at T20 compared with T3. These results suggest that glycogenolysis in contracting skeletal muscle is reduced during exercise when the rise in body core temperature is attenuated. These changes in carbohydrate metabolism appear to be influenced by alterations in muscle temperature and/or sympatho-adrenal activity.

Adrenal Glands↗
PubMed1996

Influence of elevated muscle temperature on metabolism during intense, dynamic exercise.

This study examined the effects of elevated muscle temperature on muscle metabolism during exercise. Seven active but untrained men completed two cycle ergometer trials for 2 min at a workload estimated to require 115% maximal oxygen uptake (VO2) either without pretreatment (CT) or after having their thigh wrapped in a heating blanket for 60 min before exercise (HT). HT increased (P < 0.01) muscle temperature (Tm) and resulted in a difference in Tm between the two trials before (delta = 1.9 +/- 0.1 degrees C, P < 0.01) and after exercise (delta = 0.6 +/- 0.2 degree C, P < 0.05). HT did not affect rectal temperature or plasma catecholamines. In addition, these parameters were not different between CT and HT either before or after exercise. No differences in resting intramuscular concentrations of the adenine nucleotides (ATP, ADP, AMP) or their degradation products (inosine 5'-monophosphate, ammonia), lactate, glycogen, creatine phosphate, or creatine were observed between HT and CT. During exercise, the magnitude of ATP degradation and inosine 5'-monophosphate and ammonia accumulation was higher (P < 0.05) in HT compared with CT. Although preexercise concentrations of glycogen and lactate were not different between the two trials, postexercise lactate concentration was higher (P < 0.05) and glycogen lower (P < 0.05) in HT compared with CT. In addition, net muscle glycogen use was higher (P < 0.05) in HT. It is concluded that an elevated Tm per se increases muscle glycogenolysis, glycolysis, and high-energy phosphate degradation during exercise. These alterations may be the result of an increased rate of ATP turnover associated with the exercise and/or changes in the anaerobic/aerobic contribution to ATP resynthesis.

Adenosine Diphosphate↗
PubMed1995

Effect of creatine supplementation on intramuscular TCr, metabolism and performance during intermittent, supramaximal exercise in humans.

This study examined the effect of (a) creatine supplementation on exercise metabolism and performance and (b) changes in intramuscular total creatine stores following a 5 day supplementation period and a 28 day wash-out period. Six men performed four exercise trials, each consisting of four 1 min cycling bouts, punctuated by 1 min of rest followed by a fifth bout to fatigue, all at a workload estimated to require 115 or 125% VO2,max. After three familiarization trials, one trial was conducted following a creatine monohydrate supplementation protocol (CREAT); the other after 28 d without creatine supplementation, in which the last 5 d involved placebo ingestion (CON). Intramuscular TCr was elevated (P < 0.05) in CREAT compared with the final familiarization trial (FAM 3) and CON. Concentrations of this metabolite in these latter trials were not different. In addition, a main effect (P < 0.05) for treatment was observed for PCr when the data from CREAT were compared with CON. In contrast, no differences were observed in the total adenine nucleotide pool (ATP+ADP+AMP), inosine 5'-monophosphate, ammonia, lactate or glycogen when comparing CREAT with CON. Despite the differences in TCr and PCr concentrations when comparing CREAT with other trials, no difference was observed in exercise duration in the fifth work bout. These data demonstrate that creatine supplementation results in an increase in TCr but this has no effect on performance during exercise of this nature, where the creatine kinase system is not the principal energy supplier. In addition 28 d without supplementation is a sufficient time to return intramuscular TCr stores to basal levels.

Adenine Nucleotides↗
PubMed1994

Y-intercept of the maximal work-duration relationship and anaerobic capacity in cyclists.

The degree to which the y-intercept (Y-int) of the linear regression of maximal work output on exercise duration represented anaerobic capacity was determined in ten well-trained male cyclists [peak oxygen uptake (VO2peak) = 69.8 (SD 4.2) ml.kg-1.min-1]. Each cyclist performed three exhausting cycle sessions on separate occasions; the mean exercise durations were 312, 243 and 141 s for the low (approximately 104% VO2peak), medium (approximately 108% VO2peak) and high (approximately 113% VO2peak) intensities respectively, and Y-int (kilojoules; joules per kilogram) was derived from the regression of work output on exercise duration. The muscle anaerobic adenosine 5'-triphosphate (ATP) yield (sigma ATP) and anaerobic capacity (AC) were estimated from changes in metabolites in the vastus lateralis muscle and blood lactate concentration during the high intensity cycling session. The activities of glycogen phosphorylase, phosphofructokinase and citrate synthase, as well as muscle buffer value (in vitro beta) were also determined. The Y-int (kilojoules) was positively correlated (P < or = 0.05) with AC (r = 0.73), sigma ATP (r = 0.70) and in vitro beta (r = 0.71); similar correlations (P < or = 0.05) were observed for Y-int (joules per kilogram). The Y-int was not correlated (P > 0.05) with any enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Muscle metabolism during exercise and heat stress in trained men: effect of acclimation.

Exercise metabolism was examined in 13 endurance athletes who exercised on three occasions for 40 min at 70% of maximal O2 uptake in an environmental chamber at either 20 degrees C and 20% relative humidity (RTT) or 40 degrees C and 20% relative humidity before (PRE ACC) or after (POST ACC) 7 days of acclimation. Exercise in the heat resulted in a lower (P < 0.05) mean O2 uptake (0.13 l/min) and higher (P < 0.01) heart rate and respiratory exchange ratio. Acclimation resulted in a lower (P < 0.01) mean heart rate and respiratory exchange ratio. Postexercise rectal temperature, muscle temperature, muscle and blood lactate, and blood glucose were higher (P < 0.01) in the PRE ACC than in the RTT trial, but all were reduced (P < 0.01) in the POST ACC compared with the PRE ACC trial. Muscle glycogenolysis and percentage of type I muscle fibers showing glycogen depletion were greater (P < 0.05) in the PRE ACC than in the RTT trial. Muscle glycogenolysis was unaffected by acclimation during exercise in the heat, although the percentage of depleted type I fibers was higher (P < 0.05) in the unacclimated state. Plasma epinephrine was higher (P < 0.01) during exercise in the heat in the unacclimated individual relative to RTT but was lower (P < 0.01) in the POST ACC than in the PRE ACC trial. The greater reliance on carbohydrate as a fuel source during exercise in the heat appears to be partially reduced after acclimation. These alterations are consistent with the observed changes in plasma epinephrine concentrations.

Acclimatization↗
PubMed1994

Influence of sprint training on human skeletal muscle purine nucleotide metabolism.

To examine the effect of sprint training on human skeletal muscle purine nucleotide metabolism, eight active untrained subjects completed a maximal 30-s sprint bout on a cycle ergometer before and after 7 wk of sprint training. Resting muscle ATP and total adenine nucleotide content were reduced (P < 0.05) by 19 and 18%, respectively, after training. Training resulted in a 52% attenuation (P < 0.05) in the magnitude of ATP depletion after exercise and a similar reduction (P < 0.05) in the accumulation of inosine 5'-monophosphate and ammonia. During recovery, muscle inosine 5'-monophosphate (P < 0.05) and inosine (P < 0.01) content were reduced after training, as was the accumulation of inosine (P < 0.05). Plasma ammonia was higher (P < 0.05) after training early in recovery; in contrast, plasma hypoxanthine concentrations were reduced (P < 0.05) during the latter stages of recovery. The attenuated resting ATP and total adenine nucleotide contents after training probably result from the acute effects of prior training sessions. The reduction in the magnitude of ATP depletion during a 30-s sprint bout after training must reflect an improved balance between ATP hydrolysis and resynthesis. It is unclear which mechanism(s) is responsible for the reduction in the magnitude of ATP degradation after training.

Adenine Nucleotides↗