Biomedical subjects

R L Lieber

Publications and source records attributed to R L Lieber.

At least 37 records · Page 2Linked to original sources

PubMed1999

Sarcomere length varies with wrist ulnar deviation but not forearm pronation in the extensor carpi radialis brevis muscle.

Extensor carpi radialis brevis (ECRB) sarcomere length was measured in seven patients using intraoperative laser diffraction. Sarcomere length was measured with the forearm in one of four positions: wrist in neutral with regard to radial-ulnar deviation and forearm in neutral rotation, wrist in ulnar deviation and forearm in neutral rotation, wrist in neutral and forearm in pronation, and wrist in ulnar deviation and forearm in pronation. Two-way ANOVA comparing sarcomere length between the four positions revealed a significant effect of ulnar deviation (p < 0.05), no significant effect of pronation (p > 0.7) and no significant interaction (p > 0.9). These results demonstrate that the axes of forearm rotation and wrist radial-ulnar deviation act independently, at least with regard to the ECRB and have implications regarding the etiology of tennis elbow.

Adult↗

PubMed1999

Wrist and digital joint motion produce unique flexor tendon force and excursion in the canine forelimb.

The force and excursion within the canine digital flexor tendons were measured during passive joint manipulations that simulate those used during rehabilitation after flexor tendon repair and during active muscle contraction, simulating the active rehabilitation protocol. Tendon force was measured using a small buckle placed upon the tendon while excursion was measured using a suture marker and video analysis method. Passive finger motion imposed with the wrist flexed resulted in dramatically lower tendon force (approximately 5 N) compared to passive motion imposed with the wrist extended (approximately 17 N). Lower excursions were seen at the level of the proximal interphalangeal joint with the wrist flexed (approximately 1.5 mm) while high excursion was observed when the wrist was extended or when synergistic finger and wrist motion were imposed (approximately 3.5 mm). Bivariate discriminant analysis of both force and excursion data revealed a natural clustering of the data into three general mechanical paradigms. With the wrist extended and with either one finger or four fingers manipulated, tendons experienced high loads of approximately 1500 g and high excursions of approximately 3.5 mm. In contrast, the same manipulations performed with the wrist flexed resulted in low tendon forces (4-8 N) and low tendon excursions of approximately 1.5 mm. Synergistic wrist and finger manipulation provided the third paradigm where tendon force was relatively low (approximately 4 N) but excursion was as high as those seen in the groups which were manipulated with the wrist extended. Active muscle contraction produced a modest tendon excursion (approximately 1 mm) and high or low tendon force with the wrist extended or flexed, respectively. These data provide the basis for experimentally testable hypotheses with regard to the factors that most significantly affect functional recovery after digital flexor tendon injury and define the normal mechanical operating characteristics of these tendons.

Animals↗

PubMed1999

Mechanisms of muscle injury after eccentric contraction.

Eccentric contractions of skeletal muscles produce injury and, ultimately, muscle strengthening. Current data suggests that the earliest events associated with injury are mechanical in nature and may be based primarily on the sarcomere strain experienced by the muscle. In this review, recent experimental data, primarily from rabbit dorsiflexor muscles, are used to provide general information regarding the factors that cause injury and means for preventing injury. Mechanical experiments reveal that excessive sarcomere strain is the primary cause of injury. We hypothesize that excessive strain permits extracellular or intracellular membrane disruption that may permit hydrolysis of structural proteins leading to the myofibrillar disruption that is commonly observed. Inflammation that occurs after injury actually further degrades the tissue, but prevention of the inflammation leads to a long-term loss in muscle function. Simple treatments such as increasing muscle oxidative capacity ("getting into shape") or cyclic stress-relaxation of tissue ("stretching out") have no measurable effect on the magnitude of muscle injury that occurs. Ultimately, an improved understanding of the damage mechanism may improve our ability to provide rehabilitative and strengthening prescriptions that have a rational scientific basis.

Animals↗

PubMed1999

Wrist extensor muscle pathology in lateral epicondylitis.

The morphology of the extensor carpi radialis brevis (ECRB) muscle was investigated in 20 patients with longstanding lateral epicondylitis. Muscle biopsies were obtained from the proximal or distal portion of the ECRB and analysed by enzyme- and immunohistochemical methods. Morphological abnormalities were significantly more frequent in patients than controls and included moth-eaten fibres, fibre necrosis and signs of muscle fibre regeneration as well as higher percentages of the fast-twitch oxidative (type 2A) fibre type. Changes were equally distributed proximally and distally. It is concluded that these changes, directly or indirectly, may reflect the cumulative effect of mechanical and/or metabolic overload and that decreased muscular performance in patients with lateral epicondylitis may be due to both elbow pain and physical damage to the ECRB muscle.

Adult↗

PubMed1999

Transcript-specific mRNA trafficking based on the distribution of coexpressed myosin isoforms.

mRNAs encoding four myosin heavy chain (MHC) isoforms were localized in rat skeletal muscle fibers by in situ hybridization. The ratio of MHC transcript signal in the fiber core compared to the fiber periphery was quantified using image analysis. Two distinct patterns of subcellular localization were observed. Type 1 (beta-cardiac) and type 2A MHC mRNAs were located preferentially in the muscle fiber periphery, while type 2B and type 2X mRNAs were distributed homogeneously across the fiber cross section. Since most normal muscle fibers express only a single MHC isoform, this difference in mRNA distribution could reflect either variation in the localization of the synthetic apparatus across different fiber types or differences in the trafficking of different MHC transcripts. To examine the basis for the observed differential distribution in normal muscles, mRNA distribution was assessed in muscle fibers that coexpressed multiple isoforms of the fast MHCs (i.e. types 2A, 2X and 2B), which occurred either in the combination type 2A/2X or type 2X/2B. The quantitative mRNA distribution seen in muscle fibers expressing a single isoform was not significantly different compared to that observed for mRNAs coexpressed in the same fiber (p > 0.6). Given the size similarity and homology of our riboprobes, these data suggest that their subcellular localization may be determined by relatively small differences in the sequences of the mRNAs, perhaps by differential binding of RNA sequence motifs to cytoskeletal elements.

Animals↗

PubMed1999

Skeletal muscle myosin II structure and function.

Recent experimental advances in structural biology, biophysics, and molecular biology have dramatically increased our understanding of the molecular mechanism of muscle contraction, as well as the assembly of myosin filaments. Future studies are required to detail, for example, the molecular cause of the conformational change during the power stroke and ATP hydrolysis, as well as the nature of the communication between nucleotide and actin binding sites. Based on the structural and functional homology between myosin and other molecular motors, these findings have implications not only for understanding muscle contraction, but for understanding numerous aspects of motility in all cellular systems as well.

Actins↗

PubMed1998

Four novel myosin heavy chain transcripts define a molecular basis for muscle fibre types in Rana pipiens.

1. Differential expression of myosin heavy chain (MHC) isoforms dramatically affects mechanical and energetic properties of skeletal muscle fibre types. As many as five different fibre types, each with different mechanical properties, have been reported in frog hindlimb muscles. However, only two frog MHC isoforms have previously been detected by SDS-PAGE and only one adult hindlimb MHC isoform has been cloned. 2. In the present study, four different fibre types (type 1, type 2, type 3 and tonic) were initially identified in adult Rana pipiens anterior tibialis muscle based on myosin ATPase histochemistry, size and location. Each fibre type exhibited unique reactivity to a panel of MHC monoclonal antibodies. Single fibre analysis using SDS-PAGE revealed that MHCs from immunohistochemically defined type 1, type 2 and type 3 fibres ran as three distinct isoform bands, while MHC of tonic fibres co-migrated with type 1 MHC. The combined data from immunohistochemistry and SDS-PAGE suggests that Rana fibre types are composed of four different MHCs. 3. Four novel MHC cDNAs were cloned and expression of the corresponding transcripts was measured in single immuno-identified fibres using specific polymerase chain reaction (PCR) primer pairs. Each of the four transcripts was found to be primarily expressed in a different one of the four fibre types. 4. Coexpression of MHC isoforms was observed only between types 1/2 and types 2/3 at both the protein and mRNA level. 5. These data provide a molecular basis for differentiation between frog fibre types and permit future molecular studies of MHC structure/function and gene regulation in this classic physiological system. 6. Comparison of sequence homology among amphibian, avian and mammalian MHC families supports the concept of independent evolution of fast MHC genes within vertebrate classes subsequent to the amphibian/avian/mammalian radiation.

Adenosine Triphosphatases↗

PubMed1998

Segmental muscle fiber lesions after repetitive eccentric contractions.

Immunohistochemical and electron-microscopic techniques were used to analyze the extensor digitorum longus muscles of New Zealand White rabbits 1 h, 1 day, 3, 7, and 28 days after repetitive eccentric contractions. Loss of the cytoskeletal protein desmin was the earliest manifestation of injury. Apart from 1 h post-exercise, all desmin-negative fibers stained positively with antibody to plasma fibronectin, indicating loss of cellular integrity accompanying cytoskeletal disruption. Fiber sizes were significantly increased from 1-7 days after exercise. The large (hyaline) fibers found in histological sections after repetitive eccentric contractions resulted from segmental hypercontraction of the fiber. This phenomenon occurred proximally and distally to plasma membrane lesions of the muscle fiber and necrosis and manifested itself as very short sarcomere lengths. Thus, in serial sections, staining characteristics, sizes and shapes of one and the same fiber often varied dramatically. We conclude that the following sequence of events occurs: cytoskeletal disruptions, loss of myofibrillar registry, i.e., Z-disk streaming and A-band disorganization, and loss of cell integrity as manifested by intracellular plasma fibronectin stain, hypercontracted regions, and invasion of cells. When a fiber is disrupted, the remaining intact fibers apparently take up the tension put on the muscle and later fewer fibers are subjected to eccentric contractions.

Animals↗

PubMed1998

Evidence for muscle attachment at relatively long lengths in tendon transfer surgery.

Sarcomere length was measured intraoperatively during 22 tendon transfers about the wrist primarily involving the flexor carpi ulnaris (15), but also including the extensor carpi radialis longus (4) and brachioradialis (3). Muscle tension during transfer was chosen based on traditional guidelines suggested for optimal function. After these criteria were used, it was determined that sarcomere lengths were consistently much longer than optimal lengths, even to the point of resulting in zero active tension generation. Average sarcomere length after transfer was 3.78+/-0.52 microm (mean+/-SD), which was significantly different than optimal sarcomere length (2.8 microm) in human skeletal muscle. Muscles were predicted to generate on average-on the basis of the 3.78-microm sarcomere length-only 28% of maximum active force. This appeared to be due to the fact that passive tension in upper-extremity skeletal muscles becomes important at only relatively long lengths. It is suggested that the use of passive tension as the major factor guiding intraoperative decision making results in overstretch of the muscle-tendon unit and accompanying low active force generation.

Humans↗

PubMed1998

The role of ulnar nerve transposition in ulnar nerve repair: a cadaver study.

Ulnar nerve transposition at the elbow is recommended to diminish nerve gaps during neurorrhaphy. We undertook a cadaver study to determine the gap distance that can be overcome by subcutaneous transposition at the elbow, evaluating lacerations 2.0 cm distal to the medial epicondyle and 2.0 cm proximal to the wrist crease. With a 100-g load on each nerve stump, gaps that could be overcome were measured before and after transposition in different elbow and wrist positions. For the distal forearm lacerations, wrist position significantly affected nerve gap, while transposition and elbow position did not. Nerve gap was significantly reduced by approximately 11 mm with wrist flexion from 0 degrees to 45 degrees. For proximal forearm lacerations, gap distance was significantly affected by transposition and was dependent to a greater extent on the interaction between transposition and elbow position, with wrist position having no effect. A clinically relevant scenario for the proximal laceration compared the pretransposition gap with the elbow and wrist at neutral with the posttransposition gap with the elbow and wrist flexed. Posttransposition gap reduction, with elbow and wrist flexion at 45 degrees, was approximately 9 mm and was not significant. To span a gap near the elbow, we estimate that more than 45 degrees of elbow flexion is required.

Aged↗

PubMed1998

Musculoskeletal balance of the human wrist elucidated using intraoperative laser diffraction.

This review describes a series of experiments in which sarcomere length was measured in human wrist muscles to understand their design. Sarcomere length measurements were combined with studies on cadaveric extremities to generate biomechanical models of human wrist function and to provide insights into the mechanism by which wrist strength balance is achieved. Intraoperative measurements of the human extensor carpi radialis brevis (ECRB) muscle during wrist joint rotation reveal that this muscle appears to be designed to operate on the descending limb of its length-tension curve and generates maximum tension with the wrist fully extended. Interestingly, the synergistic extensor carpi radialis longus (ECRL) also operates on its descending limb but over a much narrower sarcomere length range. This is due to the longer fibers and smaller wrist extension moment arm of the ECRL compared to the ECRB. Sarcomere lengths measured from wrist flexors are shorter compared to the extensors. Using a combination of intrapoperative measurements on the flexor carpi ulnaris (FCU) and mechanical measurements of wrist muscles, joints and tendons, the general design of the prime wrist movers emerges: both muscle groups generate maximum force with the wrist fully extended. As the wrist flexes, force decreases due to extensor lengthening along the descending limb of their length-tension curve and flexor shortening along the ascending limb of their length-tension curve. The net result is a nearly constant ratio of flexor to extensor torque over the wrist range of motion and a wrist that is most stable in full extension. These experiments demonstrate the elegant match between muscle, tendon and joints acting at the wrist. Overall, the wrist torque motors appear to be designed for balance and control rather than maximum torque generating capacity.

Biomechanical Phenomena↗

PubMed1998

Quantitative analysis of muscle fibre type and myosin heavy chain distribution in the frog hindlimb: implications for locomotory design.

To investigate the design of the frog muscular system for jumping, fibre type distribution and myosin heavy chain (MHC) isoform composition were quantified in the hindlimb muscles of Rana pipiens. Muscles were divided into two groups: five large extensor muscles which were predicted to shorten and produce mechanical power during jumping (JP), and four much smaller muscles commonly used in muscle physiology studies, but that do not shorten or produce power during jumping (NJP). fibres were classified as one of four different types (type 1, 2, 3 or tonic) or an intermediate type (type 1-2) based on their relative myosin-ATPase reactivity and MHC immunoreactivity in muscle cross-sections according to previous nomenclature established for amphibian skeletal muscle. Type 1 fibres correspond to the fastest and most powerful of the twitch fibres, and type 3 fibres are the slowest and least powerful. Myosin-ATPase histochemistry revealed that the JP muscles were composed primarily of type 1 fibres (89%) with a small percentage of type 2 (7%) and intermediate type 1-2 fibres (4%). The fibre type composition of NJP muscles was more evenly distributed between type 1 (29%), type 2 (46%) and type 1-2 (24%) fibres. Tonic fibres comprised less than 2% of the muscle cross-section in both JP and NJP groups. Similarly, MHC composition determined by quantitative SDS-PAGE revealed that JP muscles were composed predominantly of type 1 MHC (86%), with a balance of type 2 MHC (14%). The opposite pattern was found for MHC composition in the NJP muscles: type 1 (28%), type 2 (66%) and type 3 (6%). These results demonstrate that the large extensor muscles that produce the power required for jumping have a fibre type distribution that enables them to generate high levels of mechanical power, with the type 1 isoform accounting for 85-90% of the total MHC content.

Animals↗

PubMed1998

Simultaneous stiffness and force measurements reveal subtle injury to rabbit soleus muscles.

The time course of force generation and the time course of muscle stiffness were measured in rabbit soleus muscles during eccentric contraction to understand the underlying basis for the force loss in these muscles. Muscles were activated for 600 msec every 10 sec for 30 min. Soleus muscles contracting isometrically maintained constant tension throughout the treatment period, while muscles subjected to eccentric contraction rapidly dropped tension generation by 75% within the first few minutes and then an additional 10% by the end of 30 min. This indicated a dramatic loss in force-generating ability throughout the 30 min treatment period. To estimate the relative number of cross-bridges attached during the isometric force generation phase immediately preceding each eccentric contraction, stiffness was measured during a small stretch of a magnitude equal to 1.5% of the fiber length. Initially, muscle stiffness exceeded 1300 g/mm and, as eccentric treatment progressed, stiffness decreased to about 900 g/mm. Thus, while muscle stiffness decreased by only 30% over the 30 min treatment period, isometric force decreased by 85%. In isometrically activated muscles, stiffness remained constant throughout the treatment period. These data indicate that, while soleus muscles decreased their force generating capability significantly, there were a number of cross-bridges still attached that were not generating force. In summary, the loss of force generating capacity in the rabbit soleus muscle appears to be related to a fundamental change in myosin cross-bridge properties without the more dramatic morphological changes observed in other eccentric contraction models. These results are compared and contrasted with the observations made on muscles composed primarily of fast fibers.

Animals↗

PubMed1998

Quantification of myosin heavy chain mRNA in somatic and branchial arch muscles using competitive PCR.

The purpose of this study was to quantify the type and amount of myosin heavy chain (MHC) mRNA within muscles of different developmental origins to determine whether the regulation of gene expression is comparable. Seven MHC isoforms were analyzed in rat adult limb (extensor digitorum longus, tibialis anterior, and soleus) and nonlimb (extraocular, thyroarytenoid, diaphragm, and masseter) muscles using a competitive PCR assay. An exogenous template that included oligonucleotide sequences specific for seven rat sarcomeric MHC isoforms (beta-cardiac, 2A, 2X, 2B, extraocular, embryonic, and neonatal) as well as beta-actin was constructed and used as the competitor. Only the extraocular muscle contained all seven isoforms. All seven muscles contained type 2A and type 2X MHC transcripts in varying percentages. As expected, the soleus muscle contained primarily beta-cardiac MHC (87.8 +/- 2.6%). Extraocular MHC was found only in the extraocular and thyroarytenoid muscles and in relatively small proportions (7.4 +/- 1.5% and 4.0 +/- 0.7%, respectively). Neonatal MHC was identified in extraocular (7.9 +/- 0. 3%), thyroarytenoid (4.4 +/- 0.4%), and masseter (1.0 +/- 0.2%) muscles, and embryonic MHC was identified both in extraocular (1.2 +/- 0.5%) and, unexpectedly, in soleus (0.6 +/- 0.1%) muscles. Absolute MHC mRNA mass was greatest in the masseter (106 pg/0.5 microg RNA) and least for the tibialis anterior (64 pg/0.5 microg RNA). These values suggest that MHC mRNA represents from 4 to 17% of the total mRNA pool in various skeletal muscles. Differences in MHC profile between somatic and branchial arch muscles suggest that the developmental origin of a muscle may, at least in part, be responsible for the MHC expression program that is implemented in the adult. An inverse relationship between the expression of beta-cardiac and type 2B MHC transcripts across muscles was noted, suggesting that the expression of these two isoforms may be reciprocally regulated.

Aging↗

PubMed1998

Increased oxidative capacity does not protect skeletal muscle fibers from eccentric contraction-induced injury.

Isometric electrical stimulation was delivered to rabbit dorsiflexor muscles at 10 Hz for 1 s on and 1 s off over 30 min, 5 days/wk for 3 wk to induce an increase in muscle oxidative capacity. Stimulation-trained muscles as well as untrained muscles were then subjected to a 30-min eccentric exercise bout to test whether increased oxidative capacity provided a protective effect against muscle injury. Electrical stimulation results in significant training of both the extensor digitorum longus (EDL) and tibialis anterior (TA) muscles, with EDL citrate synthase (CS) activity increasing an average of 67% (P < 0.0001) and TA CS activity increasing by 27% (P < 0.05). For all parameters measured, the magnitude of change was much greater for EDL than for TA muscle. Dorsiflexor fatigability decreased significantly during the 3-wk training period (P < 0.0001), whereas the EDL TA individually showed strong decreasing trends in fatigability after training. TA and EDL capillary density measured histomorphometrically increased from 839 +/- 56 to 1,026 +/- 71 mm-2 (P = 0.07) and from 589 +/- 37 to 792 +/- 66 mm-2 (P < 0.05), respectively. TA and EDL capillary-to-fiber ratio increased from 1.32 +/- 0.10 to 1.55 +/- 0.16 (P > 0.2) and 1.08 +/- 0.07 to 1.36 +/- 0.14 (P > 0.1), respectively. Type 2A fiber type percentage increased after stimulation training by 68% (P < 0.0001) for the EDL and by 32% (P > 0.1) for the TA at the expense of type 2D fibers. Despite the large training effect for the EDL and the modest training effect for the TA, no differences were observed between stimulation-trained and untrained groups for maximum dorsiflexion torque (P > 0.3) or maximum tetanic tension (P > 0.3) after eccentric contraction-induced injury. Additionally, no significant correlation was observed between CS activity and maximum tetanic tension after eccentric contraction-induced injury for either muscle (P > 0.2). Thus we conclude that increasing muscle oxidative capacity by isometric electrical stimulation training did not protect muscle against eccentric contraction-induced injury.

Animals↗

PubMed1998

Sarcomere number adaptation after retinaculum transection in adult mice.

Skeletal muscle has been shown to adjust serial sarcomere number in response to chronic static length changes. However, the adaptive responses to alterations in the dynamic environment are less well defined. The adaptations of the adult mouse tibialis anterior (TA) muscle to altered length and excursion were investigated by surgical transection of the flexor retinaculum. TA moment arm and muscle excursion increased by 38 +/- 7% (mean +/- S.E.M.) and fully extended (plantarflexed) muscle length was decreased by 8% after flexor retinaculum transection. In spite of the significant shortening of the muscle in full plantar- and dorsiflexion, serial sarcomere number decreased by 10 +/- 1% after 2 weeks of recovery. Gait analysis of these transected animals revealed a 14 +/- 3% decrease in dorsiflexion angular velocity after transection. The decrease in angular velocity was less than the increase in moment arm and, as a result, muscle velocity was calculated to increase by 20 +/- 4%. These data suggested that the muscle adapted in response to the underlying change in length, irrespective of the altered excursion or velocity.

Adaptation, Physiological↗

PubMed1997

Growth hormone secretagogue increases muscle strength during remobilization after canine hindlimb immobilization.

Twenty-two beagles were divided into two equal groups, and the right hindlimb of each animal was immobilized at 105 degrees of knee flexion by external fixation. After 10 weeks of fixation, the device was removed, allowing free mobility for the following 5 weeks. Each day throughout the 15 weeks, one group received a growth hormone secretagogue (treatment) at a dose of 5 mg/kg, and the other received a lactose placebo (control). At weeks 0, 10, and 15, strength as indicated by maximum isometric extension torque was measured in the right hindlimb, biopsies of the vastus lateralis muscle were taken, and the dogs were weighed. Weekly blood samples were analyzed for insulin-like growth factor-1, blood urea nitrogen, and creatine phosphokinase. Between weeks 0 and 10, tetanic torque declined by about 60% (p < 0.001) in both groups, with no significant difference between the groups (p > 0.7). Between weeks 10 and 15, tetanic torque in the treated group increased by 0.81 Nm; this was significantly greater than the increase of 0.25 Nm in the placebo group (p < 0.05). The diameters of slow (type-1) and fast (type-2) fibers measured from the vastus lateralis muscle followed the same trend. At all time points, fiber diameter correlated strongly with torque; this argues against nonmuscular causes such as nerve injury for strength loss. The mean levels of insulin-like growth factor-1 increased 100% by week 4 in the treated group and remained elevated by about 60% throughout the experiment. Levels of insulin-like growth factor-1 in the placebo group decreased 30% within week 1 and remained depressed throughout the experiment. Our interpretation of these data suggests that the growth hormone secretagogue elevated levels of serum insulin-like growth factor-1, which in turn increased the size and strength of the quadriceps muscle during remobilization. These data may ultimately have therapeutic application to humans during rehabilitation after prolonged inactivity.

Animals↗

PubMed1997

Anatomy of the radial nerve motor branches in the forearm.

Knowledge of radial nerve motor branch anatomy is important when performing surgery in its vicinity, neurorrhaphy, and nerve blocks and for understanding the rate and order of recovery of muscle function after injury. Twenty normal fresh cadaver arms were dissected to quantitate radial nerve motor branch anatomy in the forearm. Though variable in individual specimens, innervation order from proximal to distal (based on mean shortest branch lengths) was brachioradialis, extensor carpi radialis longus, supinator, extensor carpi radialis brevis, extensor digitorum communis, extensor carpi ulnaris, extensor digiti quinti, abductor policis longus, extensor policis longus, extensor policis brevis, and extensor indicis proprius. In 10 specimens, branches innervated the branchialis. Mean distances from a point 100 mm proximal to the lateral epicondyle to the muscle measured along the shortest nerve branch ranged from 97.2 mm for the brachioradialis to 299.8 mm for the EIP. The mean number of muscular branches ranged from 1.1 in the EIP to 4.6 in the EDC. Mean nerve length from the radial styloid to the last motor branch was 115.8 mm.

Cadaver↗