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Biomedical subjects

G R Adams

Publications and source records attributed to G R Adams.

At least 19 recordsLinked to original sources

Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle.

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid [creatine depletion juvenile (CDJ) group]. Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens [normal diet adult and creatine depletion adult (CDA) groups]. After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC distribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC transitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of animals to be used.

Aging

Interaction of chronic creatine depletion and muscle unloading: effects on postural locomotor muscles.

In some rodent skeletal muscles, hindlimb non-weight-bearing activity induces a shift in the expression of myosin heavy chains (MHCs) that favors the type II isoforms at the expense of type I. Chemically induced chronic creatine depletion results in isomyosin shifts favoring expression of type I MHCs. In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Female Sprague-Dawley rats weighing 247 +/- 8 g were randomly assigned to four groups: 1) normal diet control, 2) beta-GPA control (BC), 3) normal diet suspended (NS), and 4) beta-GPA suspended (BS). BC and BS animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of short-term unweighting on human skeletal muscle strength and size.

This study examined the effect of short-term unweighting on strength and size of lower limb muscle groups to predict probable responses to planned 16-d Shuttle flights. Subjects were 10 healthy males, exposed to 16 d of lower limb suspension (LLS). All ambulatory activity was performed on crutches while wearing a shoe with a 10-cm thick sole on the right foot. This eliminated ground contact by the left foot, and thereby, body weight bearing by the left lower limb. Biopsies of the left vastus lateralis muscle and T1 weighted magnetic resonance (MR) images (1.5 Tesla, TR/TE 600/20, 4 nex, 48 cm rectangular FOV, 10 mm transaxial slices at 5-mm intervals) of both thighs were used to examine muscle morphology. The in vivo speed-torque relation for the left and right quadriceps femoris (QF) muscle group was used to measure strength. Fiber type composition and average cross-sectional area were not altered by LLS. The speed-torque relation for the left QF was down-shifted 12% (p < 0.05) after LLS. There was no effect of speed or type of muscle action (eccentric, isometric, or concentric). The speed-torque relation for the right QF showed no change after LLS. Average cross-sectional area of the left QF in eight MR images of the mid-thigh decreased (p < 0.05) 8% with LLS (70 +/- 3 to 64 +/- 4 cm2), while the right QF showed no change (72 +/- 4 to 72 +/- 4 cm2). The hamstring muscle group showed no change in average cross-sectional area after LLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity.

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

Animals

Skeletal muscle responses to lower limb suspension in humans.

Eight subjects participated in a 6-wk unilateral lower limb suspension (ULLS) study to determine the influence of reduced weight bearing on human skeletal muscle morphology. The right shoe was outfitted with a platform sole that prevented the left foot from bearing weight while walking with crutches, yet it allowed freedom of movement about the ankle, knee, and hip. Magnetic resonance images pre- and post-ULLS showed that thigh muscle cross-sectional area (CSA) decreased (P less than 0.05) 12% in the suspended left lower limb, whereas right thigh muscle CSA did not change. Likewise, magnetic resonance images collected post-ULLS showed that muscle CSA was 14% smaller (P less than 0.05) in the left than in the right leg. The decrease in muscle CSA of the thigh was due to a twofold greater response of the knee extensors (-16%, P less than 0.05) than knee flexors (-7%, P less than 0.05). The rectus femoris muscle of the knee extensors showed no change in CSA, whereas the three vastus muscles showed similar decreases of approximately 16% (P less than 0.05). The apparent atrophy in the leg was due mainly to reductions in CSA of the soleus (-17%) and gastrocnemius muscles (-26%). Biopsies of the left vastus lateralis pre- and post-ULLS showed a 14% decrease (P less than 0.05) in average fiber CSA. The decrease was evident in both type I (-12%) and II (-15%) fibers. The number of capillaries surrounding the different fiber types was unchanged after ULLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases

Magnetic resonance imaging and electromyography as indexes of muscle function.

Electromyography (EMG) is commonly used to determine the electrical activity of skeletal muscle during contraction. To date, independent verification of the relationship between muscle use and EMG has not been provided. It has recently been shown that relaxation- (e.g., T2) weighted magnetic resonance images (MRI) of skeletal muscle demonstrate exercise-induced contrast enhancement that is graded with exercise intensity. This study was conducted to test the hypothesis that exercise-induced magnetic resonance (MR) contrast shifts would relate to EMG amplitude if both measures reflect muscle use during exercise. Both MRI and EMG data were collected for separate eccentric (ECC) and concentric (CON) exercise of increasing intensity to take advantage of the fact that the rate of increase and amplitude of EMG activity are markedly greater for CON muscle actions. Seven subjects 30 +/- 2 (SE) yr old performed five sets of 10 CON or ECC arm curls with each of four resistances representing 40, 60, 80, and 100% of their 10 repetition maximum for CON curls. There was 1.5 min between sets and 30 min between bouts (5 sets of 10 actions at each relative resistance). Multiple echo, transaxial T2-weighted MR images (1.5 T, TR/TE 2,000/30) were collected from a 7-cm region in the middle of the arm before exercise and immediately after each bout. Surface EMG signals were collected from both heads of the biceps brachii and the long head of the triceps brachii muscles. CON and ECC actions resulted in increased integrated EMG (IEMG) and T2 values that were strongly related (r = 0.99, P < 0.05) with relative resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Adaptations to unilateral lower limb suspension in humans.

This study examined the effect of unilateral lower limb suspension (ULLS) on neuromuscular function in humans. Eight subjects (31 +/- 4 years old) performed all ambulatory activity on crutches for 6 weeks while wearing a shoe with a 10-cm sole on the right foot to unweight the left lower limb. Knee extensor (KE) torque during eccentric, concentric, and isometric actions, and electromyography (EMG) of m. vastus lateralis (m. VL), m. gastrocnemius medialis (m. GM) and m. soleus (m. SL) during isometric actions were assessed pre-ULLS, post-ULLS, and after 4 d of recovery. Average muscle cross-sectional area (CSA) of the KE was measured pre- and post-ULLS and that of the ankle extensors (AE) post-ULLS using magnetic resonance imaging. Strength of the KE of the suspended left limb was reduced (p less than 0.05) 21 and 15%, respectively, after ULLS and 4 d later. Average muscle CSA of the left KE decreased (p less than 0.05) 16%. The KE of the non-suspended right limb showed no changes in muscle CSA. Thus, average muscle CSA of the KE of the suspended limb was 17% less (p less than 0.05) than that of the non-suspended limb. Average muscle CSA of the AE, likewise, was smaller (18%, p less than 0.05) in the left than right leg after ULLS. Maximal integrated EMG of VL and overall mean power frequency of GM and SL for submaximal isometric actions were both decreased (p less than 0.05) post-ULLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Effect of decreased pH on force and phosphocreatine in mammalian skeletal muscle.

Phosphocreatine (PCr) and intracellular pH changes were monitored by 31P-NMR spectroscopy in isolated, arterially perfused cat biceps and soleus muscles, while the pH of the CO2-bicarbonate buffered perfusate was decreased from 7.1-7.4 to 6.4-6.7 by increasing the CO2 in the equilibrating gas from 5 to up to 70%. In biceps (fast twitch) muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force decreased by 8%, but the rise and relaxation times of tetanic were not significantly changed. In soleus muscles, intracellular pH decreased from 7.0 to 6.6 (30% CO2, 30 degrees C), peak tetanic force was unchanged, but the rise and relaxation times of tetani were increased by 27 and 112%, respectively. In both muscles greater decreases in tetanic force were observed during repetitive or ischemic stimulation, which resulted in intracellular pH similar to that produced by hypercapnia. Contrary to previous reports, there was no significant decrease in PCr level in either muscle type with decreased intracellular pH. In the soleus at 30 degrees C there was a significant increase in PCr level with decreased pH.

Animals

Hypercapnic acidosis and increased H2PO4- concentration do not decrease force in cat skeletal muscle.

Peak tetanic tension was measured during acidosis resulting from either hypercapnia or repetitive tetanic stimulation in isolated, arterially perfused cat biceps brachii (predominantly fast twitch) or soleus (slow twitch) muscles. Phosphocreatine (PCr), Pi, intracellular pH (pHi), and extracellular pH (pHo) were monitored by 31P-nuclear magnetic resonance spectroscopy. During repetitive stimulation under normocapnic conditions (5% CO2, pHo 7.4) Pi increased, pHi decreased from 7.1 to 6.3, and there were significant correlations between both pHi and calculated [H2PO4-] vs. peak tetanic force in both muscle types. However, hypercapnic perfusion (70% CO2, pHo, 6.7, pHi 6.4-6.5) had no effect on peak tetanic force, and there was no significant correlation between pHi or [H2PO4-] during hypercapnia in either muscle. The results indicate that decreased peak tetanic force during repetitive stimulation is not directly due to changes in pHi or diprotonated phosphate.

Acidosis

Stoichiometry of phosphocreatine and inorganic phosphate changes in rat skeletal muscle.

The apparent T1's of phosphate metabolites were measured during and after series of twitch contractions in gastrocnemius muscles of pentobarbital-anesthetized rats by steady-state progressive saturation using spatially-selective composite pulses. There was no significant change in apparent T1's of inorganic phosphate (Pi), phosphocreatine (PCr), or the three phosphates of ATP. There was a 5-10% decrease in the sum of Pi and PCr integrals, and in the sum of the gamma- and beta- phosphates of ATP during stimulation, but no significant change in the ratio (Pi + PCr)/(gamma-ATP + beta-ATP). The results indicate that there is no selective decrease in NMR observable Pi during or after a series of muscle contractions.

Adenosine Triphosphate

Direct relationship between proton T2 and exercise intensity in skeletal muscle MR images.

Exercise selectively increases the signal intensities (SI) of active muscles in T2-weighted magnetic resonance (MR) images. If these SI increases are graded with exercise intensity, the identification of muscle recruitment patterns may be possible using MR imaging. The purpose of this study was to determine the effect of force generation during exercise on muscle T2 values. Also, we examined the effects of extracellular fluid volume (ECV) expansion on muscle T2 values. Transaxial midcalf images were collected before and after exercise on eight volunteers in a 1.5T GE magnet using a standard spin echo sequence. Exercise consisted of three consecutive bouts of ankle dorsiflexion against graded loads. Three subjects also underwent brief bouts of lower leg venous occlusion (ECV expansion) during and in addition to the exercise protocol. T2 values for the dorsiflexors significantly increased after exercise. Greater mean force produced during exercise caused greater increases in T2 after exercise (T2 = 29.6 +/- 0.9 X Force). Exercise and venous occlusion caused equivalent increases in muscle cross-sectional area. These equivalent increases in ECV were not accompanied by equivalent increases in muscle T2; venous occlusion alone caused less than a 5% increase in T2 while exercise caused a 14% to 25% increase. Consequently, a direct relationship between increases in T2 and in ECV after exercise was not established. Venous occlusion during exercise, however, did significantly augment the increase in T2 and ECV of the anterior compartment muscles. Contrast enhancement among muscles after exercise in T2-weighted MR images is dependent on generated force during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Muscle buffer capacity estimated from pH changes during rest-to-work transitions.

Gated phosphorus nuclear magnetic resonance (31P-NMR) spectra were acquired after 5 or 9 s of 5-Hz stimulation in rat and cat skeletal muscles, respectively. Net phosphocreatine (PCr) hydrolysis was associated with an intracellular alkalinization of 0.08 +/- 0.01 and 0.05 +/- 0.003 pH units in isolated perfused cat biceps and soleus, respectively, and 0.12 +/- 0.02 in the superficial predominantly fast-twitch white portion of gastrocnemius of anesthetized rats. The net change in [H+] expected from PCr hydrolysis was calculated, and apparent buffer capacity (beta) in intact muscles was calculated from beta = delta [H+]/delta pH. The beta of the same muscle types was also estimated from titration of muscle homogenates between pH 6.0 and 8.0. The contribution of Pi to total beta of the homogenates was subtracted to ascertain the non-Pi beta for each muscle. The non-Pi beta values were added to the actual amount of Pi present in the stimulated muscles to calculate a predicted beta at pH 7. The apparent beta calculated from PCr and pH changes in intact muscles and the predicted beta from homogenate titrations were in good agreement (38 +/- 9 vs. 38 slykes in cat biceps, 21 +/- 7 vs. 30 in cat soleus, and 30 +/- 6 vs. 27 in rat gastrocnemius). The results indicate that changes in pH during the first few seconds of contraction can be entirely accounted for by proton consumption via net PCr hydrolysis.

Animals

Utility of AICAr for metabolic studies is diminished by systemic effects in situ.

It has been reported that intraperitoneal infusion of 5-amino-4-imidazolecarboxamide riboside (AICAr) inhibits the purine nucleotide cycle, resulting in rapid fatigue of isometric twitch force during stimulation of rat muscle. In this study, peak isometric twitch force was recorded from gastrocnemius muscles of pentobarbital-anesthetized rats stimulated in situ at 0.75 Hz after intraperitoneal infusion of 9ml/100 g body wt of 250 mM AICAr or isotonic saline. Excluding the two AICAr-infused rats that died during infusion or stimulation, there was no difference in twitch force between groups, although mean arterial pressure in the AICAr group declined to values 20 Torr below those of the control group during drug infusion. High-resolution 1H nuclear magnetic resonance (NMR) spectroscopy of extracts verified the presence of AICAr and AICA ribotide (AICAR) in muscles of experimental animals. In a second study in which rats were mounted head down in an NMR spectrometer, AICAr infusion resulted in decreased mean arterial pressure and impairment of phosphocreatine recovery after stimulation but no significant difference in twitch force during stimulation. These results demonstrate that AICAr infusion has systemic effects and that the previously reported decline in muscle force with AICAr infusion may not be attributable to purine nucleotide cycle inhibition.

Aminoimidazole Carboxamide

Glucose dependence of sequential norepinephrine contractions of vascular smooth muscle.

The effects of successive, norepinephrine (NE)-stimulated, contractions of porcine carotid artery intima-media strips as a function of recovery medium were studied. Recovery following NE stimulation required the presence of glucose in the bathing medium for subsequent force production in response to NE stimulation. Potassium stimulation following failed NE contractions produced maximal contractions. Phosphorous nuclear magnetic resonance studies under similar conditions indicated that the energy state of the tissue was not impaired during and after recovery from NE stimulation without glucose. This study shows that the phasic phase of norepinephrine-stimulated contractions is dependent on the availability of extracellular glucose during the poststimulation recovery period for successive NE contractions.

Adenosine Triphosphate

The use of 31P-NMR to study smooth muscle.

The use of 31P NMR to study smooth muscle is hindered by low metabolite concentrations and low tissue mass. These disadvantages can be overcome due to low rates of energy utilization and the temporal stability of smooth muscle. Smooth muscle free Mg++, ADP, and the creatine analogue beta-guanidinopropionate can be studied in ways distinctive from 31P NMR of striated muscle. The pharmacological effects of naturally occurring agents such as insulin, glucose, or norepinephrine, and of NMR markers such as phenylphosphonate or 3-(trimethylsilyl)-1-propane-sulfonate on both vascular smooth muscle and perfused smooth muscles can be measured. Given sufficient collection time, 31P NMR is as useful in assessing the behavior of smooth muscle as it is of other muscle types.

Adenosine Triphosphate

Sequence-specific binding of luzopeptin to DNA.

We have examined the binding of luzopeptin, an antitumor antibiotic, to five DNA fragments of varying base composition. The drug forms a tight, possibly covalent, complex with the DNA causing a reduction in mobility on nondenaturing polyacrylamide gels and some smearing of the bands consistent with intramolecular cross-linking of DNA duplexes. DNAase I and micrococcal nuclease footprinting experiments suggest that the drug binds best to regions containing alternating A and T residues, although no consensus di- or trinucleotide sequence emerges. Binding to other sites is not excluded and at moderate ligand concentrations the DNA is almost totally protected from enzyme attack. Ligand-induced enhancement of DNAase I cleavage is observed at both AT and GC-rich regions. The sequence selectivity and characteristics of luzopeptin binding are quite different from those of echinomycin, a bifunctional intercalator of related structure.

Antibiotics, Antineoplastic

The interactional teaching patterns of mothers and fathers with their popular, moderately popular, or unpopular children.

The interactional teaching strategies of mothers and fathers toward their sociometrically determined popular, moderately popular, or unpopular children, and children's responses to them were examined during a structured puzzle task in a laboratory setting. Parents of popular children used more explanations in aiding their children to complete the puzzle task than parents of moderately popular or unpopular children. Mothers were more likely to offer suggestions, use explanations, and ask questions during the puzzle task than fathers. Analysis of children's responses revealed that popular children were more likely to ignore imperatives by their parents compared with unpopular children, while unpopular children showed a tendency to be more cooperative following imperatives by parents than popular children. Finally, popular children were less likely to ignore but were more likely to go off task following suggestions by parents than either unpopular or moderately popular children. The data are discussed with respect to the possible link between parental socialization patterns and children's popularity in the peer group and the need to consider the interaction patterns in both the peer and parent-child systems for intervention purposes.

Adult