No description available.

No description available.

No description available.

Satellite cells (SCs) are muscle stem cells that stay in a metabolically and mitotically quiescent state in adult skeletal muscle until activated. In mammals, SCs are activated and enter into the cell cycle for growth and regeneration. The mechanism initiating SC activation in vivo and in vitro, mediated by nitric oxide (NO) and hepatocyte growth factor (HGF) is described in the mouse model, but not in other species. Here, we assessed SC activation by counting bromodeoxyuridine (BrdU)-immuno-positive cells, and found that SC activation in zebrafish single muscle-fibre cultures is also NO and HGF dependent, peaking at 1 mM isosorbide dinitrate (ISDN, an NO donor drug) and 10 ng/mL HGF respectively, using dose-response experiments. Moreover, HGF signalling via the c-Met receptor is involved in the SC activation pathway and is considerably affected by temperature (i.e., 21 °C). Overall, understanding NO-HGF-c-Met signalling in SC activation gives new insights on fish muscle growth and conservation of regulatory pathways between species.

Satellite cells (SCs) are muscle stem cells that stay in a metabolically and mitotically quiescent state in adult skeletal muscle until activated. In mammals, SCs are activated and enter into the cell cycle for growth and regeneration. The mechanism initiating SC activation in vivo and in vitro, mediated by nitric oxide (NO) and hepatocyte growth factor (HGF) is described in the mouse model, but not in other species. Here, we assessed SC activation by counting bromodeoxyuridine (BrdU)-immuno-positive cells, and found that SC activation in zebrafish single muscle-fibre cultures is also NO and HGF dependent, peaking at 1 mM isosorbide dinitrate (ISDN, an NO donor drug) and 10 ng/mL HGF respectively, using dose-response experiments. Moreover, HGF signalling via the c-Met receptor is involved in the SC activation pathway and is considerably affected by temperature (i.e., 21 °C). Overall, understanding NO-HGF-c-Met signalling in SC activation gives new insights on fish muscle growth and conservation of regulatory pathways between species.

When O2 uptake at the lung is used to characterise the oxidative metabolic response to increased contractile activity ( O2 kinetics) in exercising muscle, the O2 profile reflects the combined influence of all involved muscle fibres. Consequently, during high-intensity exercise that mandates activation of fibres with considerable metabolic diversity (e.g., both principal fibre types), response characteristics specific to discrete segments of the recruited pool cannot be determined. The purpose of this thesis was to identify fibre-type-specific effects of conditions that might impact O2 delivery and/or motor unit recruitment patterns on O2 kinetics by using two models that increase fibre recruitment homogeneity during exercise transitions. In four experiments, subjects initiated high-intensity exercise from a moderate baseline (i.e., performed ‘work-to-work’ transitions; M→H) to target higher-order fibres, and in two experiments, subjects cycled at extremely slow and fast pedal rates to skew recruitment toward slow- and fast-twitch fibres, respectively. At mid-range contraction frequency, O2 kinetics (as indicated by the primary time constant, τp) was slower for M→H compared to unloaded-to-high-intensity transitions (U→H) (e.g., 42 v. 33 s; Ch 4) and this slowing was ~50% greater for M→H in a supine body position (decreased oxygenation; Ch 6). Slower kinetics was also present for U→H cycling at fast compared to slow pedal rates (τp, 48 v. 31 s; Ch 8). Conversely, M→H slowing relative to U→H was absent at extreme cadences (36 v. 31 s and 53 v. 48 s for slow and fast, respectively; Ch 7). After ‘priming’ (increased oxygenation), τp was reduced for U→H after fast-cadence priming only (Ch 8) and for M→H in the supine position (Ch 6), but unaffected for upright cycle and prone knee-extension M→H, for which priming reduced the O2 slow component and delayed-onset fibre activation (as indicated by iEMG; Chs 4 and 5). These results provide evidence in exercising humans that high-order fibres possess innately slow O2 kinetics and are acutely susceptible to interventions that might alter O2 delivery to muscle.

Myogenesis is the process of skeletal muscle tissue formation where committed muscle progenitor cells differentiate into skeletal muscle fibres. Depending on the instructive cues the muscle progenitor cells receive they will differentiate into specific fibre types with different properties. The skeletal muscle fibres can be broadly classified as fast-twitch fibres or slow-twitch fibres, based on their contractile speed. However, subgroups of fast- and slow-twitch fibres with different metabolic properties, endurance and different isoforms of sarcomeric components have also been identified, adding complexity to the process of muscle tissue patterning. The skeletal muscle tissue has the capacity to regenerate throughout life. Upon muscle tissue damage muscle satellite cells are recruited to the area of injury where they proliferate and either form new fibres similar to those damaged, or fuse with existing fibres. This thesis aims to investigate the process of muscle progenitor cell proliferation and differentiation, as well as the fast-twitch fibre formation and muscle tissue patterning in the zebrafish embryo. I present results identifying the previously uncharacterised gene myl1, encoding an alkali-like myosin light chain, which is specifically expressed in fast-twitch muscle progenitors before fibre formation. Furthermore, I introduce data showing that the transcription factor six1 is expressed in Pax7+ muscle progenitor cells, which has been reported to contribute to part of the fast-twitch muscle tissue as well as to a pool of quiescent muscle satellite cells. With support from the presented data, I hypothesise that six1 keeps the Pax7+ muscle progenitor cells in a proliferative state and consequently prevents them from differentiating into muscle fibres. In addition, I demonstrate that the zebrafish fast-twitch muscle fibres can be divided into different subgroups that express unique forms of fast myosin heavy chain genes along the anterior-posterior (head-tail) axis, and that this subspecification depends on a balance between RA and Wnt signalling. Collectively I propose a previously unknown role for Six1 in zebrafish Pax7+ muscle progenitor cell proliferation and differentiation. Furthermore, I present novel data suggesting that distinct regions of the zebrafish body musculature are composed of different fast-twitch fibre types, and that this regionalisation is conserved in adult zebrafish.

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Knee function was evaluated by knee score, activity level, clinical findings and performance tests, muscle size by computerized tomography (CT), morphology by light (LM) and electron microscopy (EM), muscle function by electromyography (EMG) and isokinetic performance in 29 patients with chronic anterior cruciate ligament (ACL) tear. Preoperatively CT disclosed a significant mean atrophy of the quadriceps and nonsignificant changes of the other muscle areas of the injured leg. Morphology of m vastus lateralis of the injured leg was normal in more than half of the biopsies preoperatively, the rest showed signs of nonoptimal activation. Significant decreases in all isokinetic parameters were noticed together with significantly decreased EMG of the quadriceps muscle of the injured leg. Âfter surgical reconstruction the knees were immobilized in a cast for 6 weeks at either 30° or 70° of knee flexion. After cast removal CT showed significant decreases of all areas which also remained after training. The 30° group showed larger fibres (intracellular oedema) and more frequent morphological abnormalities than the 70° group. Fourteen weeks postoperatively the patients were allocated to either a combination of isometric and progressive resistance training or isokinetic training for 6 weeks. CT showed slightly larger areas at 20 weeks postoperatively than at 6 weeks. Morphological abnormalities were still prominent at 20 weeks postoperatively. Maximum isokinetic knee extensor mechanical output and endurance were markedly decreased at 14 weeks postoperatively but both improved progressively during the one year rehabilitation, mostly during the intensive 6 week training period but irrespective of training programme used. Fatiguability/endurance level improved over the preoperative level. Muscular work/integrated EMG was stable while EMG/t increased indicating neuromuscular relearning. The clinical result at 28 months foliowup was excellent or good in 93% of the patients and clinical stability improved in 66%. Independent upon primary knee immobilization angle or training programmes no differences could be demonstrated with respect to stability, range of motion, function or isokinetic mechanical output. Isokinetic performance was still significantly lower in the injured compared to the noninjured leg and not significantly different from the preoperative values. Morphology, only 6 cases, showed abnormalities similar to preoperative findings. In conclusion, the reason for the decreased maximum and total knee extensor performance in these patients with ACL tears is suggested to be nonoptimal activation of normal functioning muscle fibres depending on changes in knee joint receptor afferent inflow. No differences concerning the markedly improved postoperative clinical result could be seen between the different treatment modalities used. A nonoptimal muscular activation might explain the still decreased isokinetic performance present at followup. / <p>S. 1-40: sammanfattning, s. 43-137: 5 uppsatser</p> / digitalisering@umu.se

The detailed structure of the myofibrillar material in fibres from different muscles has been studied. Specimens have been obtained from human muscles and from different muscles frequently examined in experimental studies. Both light- and electron microscopical techniques have been used. Of central importance has been the method, which makes it possible to prepare ultrathin sections of frozen tissue, i.e. cryo-ult- ramicrotomy. A number of techniques for image analysis have been applied in order to obtain objektive data from the micrographs. In Paper I the present knowledge about muscle fibre structure, cryo-- sectioning and image analysis is summarized and relevant methodological problems are discussed. Paper II describes the detailed structure of the C-zone of the A-band and shows, above all, that structures occur with different repeats along the long axis of the myofibril. Paper III describes the subcellular organization of different fibres in a homogeneous (based on enzyme histochemical mATPase) population, and shows that different structural characteristies can vary independently of each other. Paper IV describes the structural diversity of the myofibrillar M-band, and paper V the diversity of the myofilament fine structure in different fibres. The results show that there is a most sophisticated, and previosly unrealized, structural specialization both within the myofibrils and between myofibrils from different fibres and muscles, even if the fibres are of the same fibre type. The findings suggest that generally used models, showing the structural organization within myofibrils and myofilaments, are oversimplifications. The fibre population is more heterogeneously built up than the common systems for fibre type classification makes one to belive. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1988, härtill 5 uppsatser.</p> / digitalisering@umu