Search PubMed⌕ Search

Biomedical subjects

R J Talmadge

Publications and source records attributed to R J Talmadge.

At least 19 recordsLinked to original sources
PubMed2002

Phenotypic adaptations in human muscle fibers 6 and 24 wk after spinal cord injury.

The effects of spinal cord injury (SCI) on the profile of sarco(endo) plasmic reticulum calcium-ATPase (SERCA) and myosin heavy chain (MHC) isoforms in individual vastus lateralis (VL) muscle fibers were determined. Biopsies from the VL were obtained from SCI subjects 6 and 24 wk postinjury (n = 6). Biopsies from nondisabled (ND) subjects were obtained at two time points 18 wk apart (n = 4). In ND subjects, the proportions of VL fibers containing MHC I, MHC IIa, and MHC IIx were 46 +/- 3, 53 +/- 3, and 1 +/- 1%, respectively. Most MHC I fibers contained SERCA2. Most MHC IIa fibers contained SERCA1. All MHC IIx fibers contained SERCA1 exclusively. SCI resulted in significant increases in fibers with MHC IIx (14 +/- 4% at 6 wk and 16 +/- 2% at 24 wk). In addition, SCI resulted in high proportions of MHC I and MHC IIa fibers with both SERCA isoforms (29% at 6 wk and 54% at 24 wk for MHC I fibers and 16% at 6 wk and 38% at 24 wk for MHC IIa fibers). Thus high proportions of VL fibers were mismatched for SERCA and MHC isoforms after SCI (19 +/- 3% at 6 wk and 36 +/- 9% at 24 wk) compared with only ~5% in ND subjects. These data suggest that, in the early time period following SCI, fast fiber isoforms of both SERCA and MHC are elevated disproportionately, resulting in fibers that are mismatched for SERCA and MHC isoforms. Thus the adaptations in SERCA and MHC isoforms appear to occur independently.

Administration, Sublingual↗
PubMed2001

Retraining the injured spinal cord.

The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up-regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down-regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

Animals↗
PubMed2001

Expression of heat shock protein 72 in atrophied rat skeletal muscles.

Changes in the expression of heat shock protein 72 (HSP72) in response to atrophic-inducing perturbations of muscle involving chronic mechanical unloading and denervation were determined. Adult male Wistar rats were assigned randomly to a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN group. Tenotomy and DEN involved cutting the Achilles tendon and removing a segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P < 0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05). Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU + TEN group. Hind limb unloading alone had little effect on the HSP72 level in either muscle. Reduced levels of HSP72 were associated with a decreased soleus (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are responsive to a chronic decrease in the levels of loading and/or activation and suggest that the neuromuscular activity level and the presence of innervation of a muscle are important factors that induce HSP72 expression.

Achilles Tendon↗
PubMed2001

Skeletal muscle calcineurin: influence of phenotype adaptation and atrophy.

Calcineurin (CaN) has been implicated as a signaling molecule that can transduce physiological stimuli (e.g., contractile activity) into molecular signals that initiate slow-fiber phenotypic gene expression and muscle growth. To determine the influence of muscle phenotype and atrophy on CaN levels in muscle, the levels of soluble CaN in rat muscles of varying phenotype, as assessed by myosin heavy chain (MHC)-isoform proportions, were determined by Western blotting. CaN levels were significantly greater in the plantaris muscle containing predominantly fast (IIx and IIb) MHC isoforms, compared with the soleus (predominantly type I MHC) or vastus intermedius (VI, contains all 4 adult MHC isoforms). Three months after a complete spinal cord transection (ST), the CaN levels in the VI muscle were significantly reduced, despite a significant increase in fast MHC isoforms. Surprisingly, the levels of CaN in the VI were highly correlated with muscle mass but not MHC isoform proportions in ST and control rats. These data demonstrate that CaN levels in skeletal muscle are highly correlated to muscle mass and that the normal relationship with phenotype is lost after ST.

Adaptation, Physiological↗
PubMed2001

Effect of a myocardial volume overload on lactate transport in skeletal muscle sarcolemmal vesicles.

This study sought to determine the effect of a myocardial volume overload (MVO) on sarcolemmal (SL) lactate (La(-)) transport and the aerobic profile of skeletal muscle. SL vesicles were obtained from female rats 10 wk after either a MVO was induced by creation of an infrarenal fistula (n = 10), or sham surgeries were performed (n = 11). Influx of (14)C-labeled L(+)-La(-) was measured at various unlabeled La(-) concentrations under zero-trans conditions. La(-) transport kinetics were determined using a Michaelis-Menten equation with an added linear component to discriminate between carrier-mediated and diffusional transport. Although heart and lung weights were significantly increased (P < 0.0001) in the MVO group, left ventricular function was only modestly altered (P < 0.05). A significant reduction in type I myosin heavy chain (MHC) in the soleus and a strong trend (P = 0.06) for a reduced type IIx MHC in the plantaris were observed in MVO rats, but no differences in citrate synthase activity or monocarboxylate transporter proteins (MCT)-1 expression were noted in any muscle. Carrier-mediated La(-) influx into SL vesicles was similar between sham and MVO (K(m) = 12 +/- 1 and 18 +/- 3 mM; apparent V(max) = 772 +/- 99 and 827 +/- 80 nmol. mg(-1). min(-1), respectively). Total influx at 100 mM was lower in MVO, and this was due to a 30% reduction in membrane diffusion. In conclusion, a 10-wk MVO did not alter MCT-mediated La(-) transport or protein expression but was associated with modest changes in myofibrillar proteins and impaired SL diffusive properties.

Animals↗
PubMed2001

Size and myonuclear domains in Rhesus soleus muscle fibers: short-term spaceflight.

The cross-sectional area (CSA), myonuclear number per mm of fiber length, and myonuclear domain (cytoplasmic volume/myonucleus) of mechanically isolated single fibers from biopsies of the soleus muscle of 5 vivarium control, 3 flight simulation and 2 flight (BION 11) Rhesus monkeys (Macaca [correction of Macacca] mulatta) were determined using confocal microscopy before and after a 14-day experimental period. Simulation monkeys were confined in chairs placed in capsules identical to those used during the flight. Fibers were classified as type I, type II or hybrid (containing both types I and II) based on myosin heavy chain (MHC) gel electrophoresis. A majority of the fibers sampled contained only type I MHC, i.e. 89, 62 and 68% for the control, simulation and flight groups, respectively. Most of the remaining fibers were hybrids, i.e. 8, 36 and 32% for the same groups. There were no significant pre-post differences in the fiber type composition for any of the experimental groups. There also were no significant pre-post differences in fiber CSA, myonuclear number or myonuclear domain. There was, however, a tendency for the fibers in the post-flight biopsies to have a smaller mean CSA and myonuclear domain (approximately 10%, p=0.07) than the fibers in the pre-flight biopsy. The combined mean cytoplasmic volume/myonucleus for all muscle fiber phenotypes in the Rhesus soleus muscle was approximately 25,000 micrometers3 and there were no differences in pre-post samples for the control and simulated groups. The cytoplasmic domains tended to be lower (p=0.08) after than before flight. No phenotype differences in cytoplasmic domains were observed. These data suggest that after a relatively short period of actual spaceflight, modest fiber atrophy occurs in the soleus muscle fibers without a concomitant change in myonuclear number.

Adaptation, Physiological↗
PubMed2000

Myosin heavy chain isoform expression following reduced neuromuscular activity: potential regulatory mechanisms.

In this review, the adaptations in myosin heavy chain (MHC) isoform expression induced by chronic reductions in neuromuscular activity (including electrical activation and load bearing) of the intact neuromuscular unit are summarized and evaluated. Several different animal models and human clinical conditions of reduced neuromuscular activity are categorized based on the manner and extent to which they alter the levels of electrical activation and load bearing, resulting in three main categories of reduced activity. These are: 1) reduced activation and load bearing (including spinal cord injury, spinal cord transection, and limb immobilization with the muscle in a shortened position); 2) reduced loading (including spaceflight, hindlimb unloading, bed rest, and unilateral limb unloading); and 3) inactivity (including spinal cord isolation and blockage of motoneuron action potential conduction by tetrodotoxin). All of the models discussed resulted in increased expression of fast MHC isoforms at the protein and/or mRNA levels in slow and fast muscles (with the possible exception of unilateral limb unloading in humans). However, the specific fast MHC isoforms that are induced (usually the MHC-IIx isoform in slow muscle and the MHC-IIb isoform in fast muscle) and the degree and rate of adaptation are dependent upon the animal species and the specific model or condition that is being studied. Recent studies designed to elucidate the mechanisms by which electrical activation and load bearing alter expression of MHC isoforms at the cellular and genetic levels are also reviewed. Two main mechanisms have been proposed, the myogenin:MyoD and calcineurin:NF-AT pathways. Collectively, the data suggest that the regulation of MHC isoform expression involves a complex interaction of multiple control mechanisms including the myogenin:MyoD and calcineurin:NF-AT pathways; however, other intracellular signaling pathways are likely to contribute.

Animals↗
PubMed2000

Persistence of myosin heavy chain-based fiber types in innervated but silenced rat fast muscle.

Myosin heavy chain (MHC) profile and size of fibers in deep and superficial regions of the adult rat medial gastrocnemius (MG) were determined after 4, 15, 30, and 60 days of inactivity induced by spinal cord isolation (SI). After 4 days, fiber size decreased by 33 to 50% and 36 to 46% in deep and superficial regions, whereas MHC composition was unaffected. By 15 days, these values were 45 to 78% and 51 to 69%, and MHC composition was shifting toward faster isoforms. By 60 days, there were no pure type I MHC fibers and increases from 1 to 18% and 78 to 93% in pure type IIb fibers in deep and superficial regions. The percentage of type I MHC (gel electrophoresis) was approximately 10 and approximately 3%, and of type IIb approximately 40 and approximately 60% in control and 60-day SI rats. Thus, adaptations in the MHC molecule occurred at a slower rate and for a longer duration than the atrophic response.

Animals↗
PubMed2000

Distinct myosin heavy chain isoform transitions in developing slow and fast cat hindlimb muscles.

The expression of myosin heavy chain (MHC) isoforms leading to adult fiber phenotypes in the tibialis anterior (TA) and soleus muscles of the cat were investigated from embryonic day 35 to 1 year after birth. Electrophoresis and immunoblotting of myofibrils demonstrated the expression of 5 different MHC isoforms, i.e. I, IIa, IIx, embryonic, and neonatal, during development. Based on electrophoresis, the adult-like MHC composition of the soleus and TA were not observed until postnatal day 40 (P40) and 120 (P120), respectively. In contrast, immunohistochemical analyses revealed that the adult-like fiber phenotype composition was attained much later (P120) in the soleus. The existence of multiple MHC isoforms in individual fibers suggested that transitions occurred until P120 in both muscles. Adult type I fibers were first observed at P1. Adult IIA fibers were first observed at P30 in the TA and P40 in the soleus. IIX fibers were not identified until P40 in the TA. The transition to the predominantly slow phenotype of the soleus involved a gradual loss of embryonic and fast isoforms accompanied by an accumulation of slow MHC. In contrast, the expression of slow and fast MHC in the fast TA muscle was relatively unchanged throughout development. These results show that the establishment of a given MHC-based fiber phenotype varies significantly between slow and fast muscles in the kitten.

Age Factors↗
PubMed2000

Fiber size and myosin phenotypes of selected rhesus lower limb muscles after a 14-day spaceflight.

Muscle biopsies were taken from the rhesus (Macaca mulatta) soleus (Sol, a slow ankle extensor), medial gastrocnemius (MG, a fast ankle extensor), tibialis anterior (TA, a fast ankle flexor), and vastus lateralis (VL, a fast knee extensor) muscles in vivarium controls (n=5) before and after either a 14-day spaceflight (Bion 11, n=2) or a 14-day ground-based flight simulation (n=3). Myosin heavy chain (MHC) composition (gel electrophoresis), fiber type distribution (immunohistochemistry), and fiber size were determined. Although there were no significant changes, each muscle showed trends towards adaptation.

Animals↗
PubMed1999

Persistence of hybrid fibers in rat soleus after spinal cord transection.

The effects of a chronic (up to 360 days) reduction in neuromuscular activity (defined as electrical activation and loading) on myosin heavy chain (MHC) isoform expression in the rat soleus muscle were studied. A complete mid-thoracic (T7-T8) spinal cord transection (ST) was used to induce a reduction in soleus muscle neuromuscular activity. Electrophoretic analyses revealed that MHC-I was progressively decreased after ST, accounting for approx. 90% of the total soleus MHC in controls and only approx. 12% 1 year after ST. The reductions in the proportion of MHC-I were countered by increases in MHC-IIa and MHC-IIx with the increase in MHC-IIx preceding the increase in MHC-IIa. Curiously, MHC-IIb was expressed only at very low levels. Thus, a complete transformation from predominantly MHC-I to MHC-IIb did not occur. Many fibers (up to approx. 80%) contained multiple MHCs (hybrid fibers) after ST. The proportion of hybrid fibers was maintained at a high level (approx. 50%) 1 year after ST. These data suggest that: 1) a prolonged reduction in neuromuscular activity was not sufficient to induce high level MHC-IIb expression by the soleus muscle; and 2) hybrid fibers were not simply transitional fibers. Thus, it appears that under appropriate conditions hybrid fibers may represent a "stable" fiber phenotype.

Animals↗
PubMed1999

Differential response of fast hindlimb extensor and flexor muscles to exercise in adult spinalized cats.

Adult cats were spinal transected (T12-13) and maintained for approximately 6 months. Spinal cats were either not trained (N-T) or trained for 30 min/day to either step on a treadmill (Stp-T) or stand (Std-T). Spinalization resulted in a decrease in the mass and maximum tension potential of the medial gastrocnemius (MG), a fast ankle extensor. These adaptations were ameliorated in Std-T but not Stp-T cats. The maximum rate of shortening was elevated by 18 (ns), 34, and 19 (ns)% in the N-T, Std-T, and Stp-T cats, respectively, a finding consistent with a shift in the percentage of fast fibers, a decrease in the percentage of fibers expressing only type I myosin heavy chain, and an increase in myofibrillar adenosine triphosphatase activity. The shift toward a faster fiber type profile in the tibialis anterior (TA), a fast ankle flexor, was of a lesser magnitude than in the MG. There were no significant effects on the contractile properties of the TA in any group of spinal cats. The greater preservation of muscle mass, shift toward faster physiological and biochemical properties, and fatigability in the MG of Std-T than Stp-T cats suggest that factors other than the level of activation and force generation must play a role in muscle homeostasis. From a clinical perspective, the results indicate that muscles innervated by motor neurons below the level of a complete spinal cord lesion are affected differentially by specific neuromuscular activity patterns.

Animals↗
PubMed1999

Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms.

Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

Adult↗
PubMed1999

Interrelationships of myofibrillar ATPase activity and metabolic properties of myosin heavy chain-based fibre types in rat skeletal muscle.

Myofibrillar ATPase (mATPase), succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPD) activities and cross-sectional area (CSA) were measured in fibres of rat medial gastrocnemius muscle using quantitative histochemistry. The same fibres were typed immunohistochemically using monoclonal antibodies specific to selected myosin heavy chain (MHC) isoforms. The values of mATPase, SDH, GPD and CSA formed a continuum, but significant differences in mean values were observed among fibre types of presumed homogeneous MHC content. Type I fibres had the lowest mATPase activity, followed in rank order by type IIA < type IID/X < type IIB. Type IIA fibres had the highest SDH activity, followed in rank order by type IID/X > type I > type IIB. The mean GPD activity was consistently ranked according to fibre type such that type IIB > type IID/X > type IIA > type I. Type IIA fibres were the smallest, type IIB fibres were the largest and types I and IID/X were of intermediate size. Significant interrelationships between mATPase, SDH, GPD and CSA values were found on a fibre-to-fibre basis. Consequently, discrimination of fibres according to their MHC content was possible on the basis of their mATPase, SDH, GPD and CSA profiles. These intrafibre interrelationships suggest that the MHC isoform is associated with phenotypic differences in contractile, metabolic and size properties of muscle fibre types.

Adenosine Triphosphatases↗
PubMed1999

Fiber size and myosin phenotypes of selected Rhesus hindlimb muscles after a 14-day spaceflight.

Open muscle biopsies were obtained from Rhesus soleus (slow ankle extensor), medial gastrocnemius (fast ankle extensor) and tibialis anterior (fast ankle flexor) muscles before and after either a 14-day spaceflight (BION 11, n=2) or ground-based flight simulation (n=3) and in time-matched controls (n=5). Fiber type distribution (immunohistochemistry), myosin heavy chain (MHC) composition (gel electrophoresis) and fiber size were determined. There was a large amount of inter-animal variability and there were no significant pre-post differences for any variable under any condition for any muscle studied. However, each muscle showed trends towards adaptation. Based on the immunohistochemical analyses, the percentage of type I fibers in the soleus was 68 and 86% in pre and 43 and 70% in post biopsies of the simulation and flight groups. The number of hybrid (containing both fast and slow MHC) fibers increased in both groups. MHC composition changed in a similar direction. Type I and hybrid fibers were 23 and 31% smaller after than before flight. In the medial gastrocnemius, type I fibers were 16, 14 and 32% smaller in post compared to pre biopsies in control, simulation and flight Rhesus. In the tibialis anterior, type I fibers were approximately 14% smaller in post- than pre-flight biopsies. As expected the soleus, a slow anti-gravity muscle, was most affected after 14 days of weightlessness. Further, slow fibers in each muscle were more responsive to microgravity than fast fibers. All changes, however, were smaller than those observed in rats after the same duration of flight. This differential effect may be related to the partial restraint of Rhesus in the chaired position compared to the free-floating position of rats in the cage and/or to differences in the contractile protein turnover rates between species.

Animals↗
PubMed1998

Training effects on soleus of cats spinal cord transected (T12-13) as adults.

Adult spinal cord transected (T12-13) cats were trained for 30 min/day, 5 days/week to either step on a treadmill (Stp-T) or stand (Std-T) for approximately 5 months. Training ameliorated soleus atrophy and enhanced maximum force capability compared to nontrained (N-T) spinal cats, with Stp-T being significantly different from N-T. Isometric twitch speed and maximum rate of shortening were unaffected by training; the soleus of all spinal groups was significantly faster than control. There was an elevation in myosin adenosine triphosphatase activity and a shift toward faster myosin heavy chain and fiber type compositions in N-T and Std-T, but not Stp-T cats. Thus, rhythmical activity involving muscle length and force changes (stepping) was more effective than a similar amount of a more static activity (standing). This specificity related to the type of training should be considered when developing rehabilitative strategies following spinal cord injury.

Animals↗
PubMed1998

Effects of inactivity on myosin heavy chain composition and size of rat soleus fibers.

Myosin heavy chain (MHC) and fiber size properties of the adult rat soleus were determined after 4-60 days of complete inactivity, i.e., lumbar spinal cord isolation. Soleus atrophy was rapid and progressive, i.e., 25% and 64% decrease in weight and 33% and 75% decrease in fiber size after 4 and 60 days of inactivity, respectively. Changes in MHC occurred at a slower rate than the atrophic response. After 15 days there was de novo expression of type IIx MHC (approximately 10%). By 60 days, type IIx MHC accounted for 33% of the total MHC content, and 7% of the fibers contained only type IIx MHC. The relative amount of type I MHC was reduced from 93% in control to 49% after 60 days of inactivity. Therefore, the effects of 60 days of inactivity suggest that during this time period at least 75% of fiber size and approximately 40% of type I MHC composition of the adult rat soleus can be attributed to activation-related events.

Animals↗