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  • 1.
    Agarkova, Irina
    et al.
    ETH-Zurich Hoenggerberg.
    Schoenauer, Roman
    ETH-Zurich Hoenggerberg.
    Ehler, Elisabeth
    King×s College London,.
    Carlsson, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Carlsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Perriard, Jean-Claude
    ETH-Zurich Hoenggerberg.
    The molecular composition of the sarcomeric M-band correlates with muscle fiber type2004Inngår i: European Journal of Cell Biology, ISSN 0171-9335, Vol. 83, nr 5, s. 193-204Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The M-band is the transverse structure that cross-links the thick filaments in the center and provides a perfect alignment of the A-band in the activated sarcomere. The molecular composition of the M-bands in adult mouse skeletal muscle is fiber-type dependent. All M-bands in fast fibers contain M-protein while M-bands in slow fibers contain a significant proportion of the EH-myomesin isoform, previously detected only in embryonic heart muscle. This fiber-type specificity develops during the first postnatal weeks. However, the ratio between the amounts of myosin and of myomesin, taken as sum of both isoforms, remains nearly constant in all studied muscles. Ultrastructural analysis demonstrates that some of the soleus fibers show a diffuse appearance of the M-band, resembling the situation in the embryonic heart. A model is proposed to explain the functional consequence of differential M-band composition for the physiological and morphological properties of sarcomeres in different muscle types.

  • 2.
    Ahlgren, Christina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Waling, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Kadi, Fawzi
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Djupsjöbacka, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Centre for Musculoskeletal Research, National Institute for Working Life, Umeå , Sweden.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Sundelin, Gunnevi
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Effects on physical performance and pain from three dynamic training programs for women with work-related trapezius myalgia2001Inngår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 33, nr 4, s. 162-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To compare training programs for women with trapezius myalgia regarding physical performance and pain, 102 women were randomized to strength, endurance, co-ordination and non-training groups. Before and after the intervention, static strength and dynamic muscular endurance in shoulder muscles were measured on a Cybex II dynamometer. Muscle activity in shoulder muscles was monitored via surface EMG. The signal amplitude ratio between the active and passive phase of repeated contractions indicated the ability to relax. Pain at present, pain in general and pain at worst were measured on visual analogue scales. After training, within group comparisons showed that the training groups rated less pain, and in the strength training group ratings of pain at worst differed from the non-training group. Using the non-training group as a reference, static strength increased in the strength and endurance training groups and muscular endurance in all training groups. The study indicates that regular exercises with strength, endurance or co-ordination training of neck/shoulder muscles might alleviate pain for women with work-related trapezius myalgia.

  • 3. Borg, Kristian
    et al.
    Stucka, Rolf
    Locke, Matthew
    Melin, Eva
    Ahlberg, Gabrielle
    Klutzny, Ursula
    Hagen, Maja von der
    Huebner, Angela
    Lochmüller, Hanns
    Wrogemann, Klaus
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Blake, Derek J
    Schoser, Benedikt
    Intragenic deletion of TRIM32 in compound heterozygotes with sarcotubular myopathy/LGMD2H2009Inngår i: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 30, nr 9, s. E831-E844Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In 2005 the commonality of sarcotubular myopathy (STM) and limb girdle muscular dystrophy type 2H (LGMD2H) was demonstrated, as both are caused by the p D487N missense mutation in TRIM32 originally found in the Manitoba Hutterite population. Recently, three novel homozygous TRIM32 mutations have been described in LGMD patients. Here we describe a three generation Swedish family clinically presenting with limb girdle muscular weakness and histological features of a microvacuolar myopathy. The two index patients were compound heterozygotes for a frameshift mutation in TRIM32 (c.1560delC ) and a 30 kb intragenic deletion, encompassing parts of intron 1 and the entire exon 2 of TRIM32. In these patients, no full-length or truncated TRIM32 could be detected. Interestingly, heterozygous family members carrying only one mutation showed mild clinical symptoms and vacuolar changes in muscle. In our family, the phenotype encompasses additionally a mild demyelinating polyneuropathic syndrome. Thus STM and LGMD2H are the result of loss of function mutations that can be either deletions or missense mutations. (c) 2009 Wiley-Liss, Inc.

  • 4.
    Carlsson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Fischer, Christine
    Karoloinska Institute.
    Sjöberg, Gunnnar
    Karoloinska Institute.
    Robson, Richard M
    Iowa Statte University.
    Sejersen, Thomas
    Karoloinska Institute.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation2002Inngår i: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 104, nr 5, s. 493-504Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with abnormal accumulations of desmin have been described in myopathies with or without cardiac involvement. Desmin deposits were sometimes associated with abnormal aggregates of other cytoskeletal proteins. In the present study we present how the cytoskeletal organisation of desmin, nestin, synemin, paranemin, plectin and alphaB-crystallin is altered in skeletal muscles from a patient with a L345P mutation in the desmin gene. In general, accumulations of desmin together with synemin, nestin, plectin and alphaB-crystallin were present between myofibrils and beneath the sarcolemma. However, as the biopsy samples were very myopathic, large variability in fibre size and fibre maturation was seen, thus the myofibrillar content and the cytoskeletal organisation varied considerably. In cultured satellite cells from the patient, desmin aggregates were not observed in initial passages, but occurred over time in culture in the form of perinuclear, peripheral or cytoplasmic deposits. Nestin colocalised to the abnormal desmin deposits to a larger extent than did vimentin. alphaB-Crystallin was only present in cells with a disrupted desmin network. Plectin was altered in a subset of cells with a disrupted desmin network, whereas synemin and paranemin were not detected. We conclude that the L345P desmin mutation has a profound influence on the cytoskeletal organisation both in vivo and in vitro, which reflects the pathogenesis of the desmin myopathy.

  • 5.
    Carlsson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Li, Z L
    Université Paris.
    Paulin, D
    Université Paris.
    Price, M G
    Baylor College of Medicine.
    Breckler, J
    San Fransisco State University.
    Robson, R M
    Iowa State University.
    Wiche, G
    University of Vienna.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Differences in the distribution of synemin, paranemin, and plectin in skeletal muscles of wild-type and desmin knock-out mice2000Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 114, nr 1, s. 39-47Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mice lacking the gene encoding for the intermediate filament protein desmin have a surprisingly normal myofibrillar organization in skeletal muscle fibers, although myopathy develops in highly used muscles. In the present study we examined how synemin, paranemin, and plectin, three key cytoskeletal proteins related to desmin, are organized in normal and desmin knock-out (K/O) mice. We show that in wild-type mice, synemin, paranemin, and plectin were colocalized with desmin in Z-disc-associated striations and at the sarcolemma. All three proteins were also present at the myotendinous junctions and in the postsynaptic area of motor endplates. In the desmin K/O mice the distribution of plectin was unaffected, whereas synemin and paranemin were partly affected. The Z-disc-associated striations were in general no longer present in between the myofibrils. In contrast, at the myotendinous and neuromuscular junctions synemin and paranemin were still present. Our study shows that plectin differs from synemin and paranemin in its binding properties to the myofibrillar Z-discs and that the cytoskeleton in junctional areas is particularly complex in its organization.

  • 6.
    Carlsson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Desmin-related myopathies in mice and man2001Inngår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 171, nr 3, s. 341-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Desmin, the main intermediate filament (IF) protein in skeletal and heart muscle cells, is of great importance as a part of the cytoskeleton. The IFs surround and interlink myofibrils, and connect the peripheral myofibrils with the sarcolemma. In myotendinous junctions and neuromuscular junctions of skeletal muscle fibres, desmin is enriched. In the heart, desmin is increased at intercalated discs, the attachment between cardiomyocytes, and it is the main component in Purkinje fibres of the conduction system. Desmin is the first muscle-specific protein to appear during myogenesis. Nevertheless, lack of desmin, as shown from experiments with desmin knockout (K/O) mice, does not influence myogenesis or myofibrillogenesis. However, the desmin knock-out mice postnatally develop a cardiomyopathy and a muscle dystrophy in highly used skeletal muscles. In other skeletal muscles the organization of myofibrils is remarkably unaffected. Thus, the main consequence of the lack of desmin is that the muscle fibres become more susceptible to damage. The loss of membrane integrity leads to a dystrophic process, with degeneration and fibrosis. In the heart cardiac failure develops, whereas in affected skeletal muscles regenerative attempts are seen. In humans, accumulations of desmin have been a hallmark for presumptive desmin myopathies. Recent investigations have shown that some families with such a myopathy have a defect in the gene coding for alphaB-crystallin, whereas others have mutations in the desmin gene. Typical features of these patients are cardiac affections and muscle weakness. Thus, mutations in the desmin gene is pathogenic for a distinct type of muscle disorder.

  • 7.
    Carlsson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Yu, Ji-Guo
    Department of Natural and Environmental Physiology, Mid Sweden University.
    Moza, Monica
    Department of Pathology and Neuroscience Program, Biomedicum Helsinki, University of Helsinki and University Central Hospital, Finland.
    Carpén, Olli
    Department of Pathology, University of Turku and Turku University Central Hospital, Finland.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Myotilin: a prominent marker of myofibrillar remodelling2007Inngår i: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 17, nr 1, s. 61-68Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Myofibrillar remodelling with insertion of sarcomeres is a typical feature of biopsies taken from persons suffering of exercise-induced delayed onset muscle soreness. Here we studied the presence of the sarcomeric protein myotilin in eccentric exercise related lesions. Myotilin is a component of sarcomeric Z-discs and it binds several other Z-disc proteins, i.e. alpha-actinin, filamin C, F-actin and FATZ. Myotilin has previously been shown to be present in nemaline rods and central cores and to be mutated in limb girdle muscular dystrophy 1A (LGMD1A) and in a subset of myofibrillar myopathies, indicating an important role in Z-disc maintenance. Our findings on non-diseased muscle affected by eccentric exercise give new information on how myotilin is associated to myofibrillar components upon remodelling. We show that myotilin was present in increased amount in lesions related to Z-disc streaming and events leading to insertion of new sarcomeres in pre-existing myofibrils and can therefore be used as a marker for myofibrillar remodelling. Interestingly, myotilin is preferentially associated with F-actin rather than with the core Z-disc protein alpha-actinin during these events. This suggests that myotilin has a key role in the dynamic molecular events mediating myofibrillar assembly in normal and diseased skeletal muscle.

  • 8.
    Carlsson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Yu, Ji-Guo
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    New aspects of obscurin in human striated muscles.2008Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 130, nr 1, s. 91-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Obscurin is a giant protein (700-800 kDa) present in both skeletal muscles and myocardium. According to animal studies, obscurin interacts with myofibrillar Z-discs during early muscle development, but is translocalised to be predominantly associated with the M-bands in mature muscles. The proposed function for obscurin is in the assembly and organisation of myosin into regular A-bands during formation of new sarcomeres. In the present study, the precise localisation of obscurin in developing and mature normal human striated muscle is presented for the first time. We show that obscurin surrounded myofibrils at the M-band level in both developing and mature human skeletal and heart muscles, which is partly at variance with that observed in animals. At maturity, obscurin also formed links between the peripheral myofibrils and the sarcolemma, and was a distinct component of the neuromuscular junctions. Obscurin should therefore be regarded as an additional component of the extrasarcomeric cytoskeleton. To test this function of obscurin, biopsies from subjects with exercise-induced delayed onset muscle soreness (DOMS) were examined. In these subjects, myofibrillar alterations related to sarcomerogenesis are observed. Our immunohistochemical analysis revealed that obscurin was never lacking in myofibrillar alterations, but was either preserved at the M-band level or diffusely spread over the sarcomeres. As myosin was absent in such areas but later reincorporated in the newly formed sarcomeres, our results support that obscurin also might play an important role in the formation and maintenance of A-bands.

  • 9.
    Edmundsson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Toolanen, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Evidence for low muscle capillary supply as a pathogenic factor in chronic compartment syndrome2010Inngår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 20, nr 6, s. 805-813Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a paucity of data regarding the pathogenesis of chronic exertional compartment syndrome (CECS), its consequences for the muscles and the effects of treatment with fasciotomy. We analyzed biopsies from the tibialis anterior muscle, from nine patients, obtained during a decompressing fasciotomy and during follow-up 1 year later. Control biopsies were obtained from nine normal subjects. Muscle capillarity, fiber-type composition and fiber area were analyzed with enzyme- and immunohistochemistry and morphometry. At baseline, CECS patients had lower capillary density (273 vs 378 capillaries/mm(2), P=0.008), lower number of capillaries around muscle fibers (4.5 vs 5.7, P=0.004) and lower number of capillaries in relation to the muscle fiber area (1.1 vs 1.5, P=0.01) compared with normal controls. The fiber-type composition and fiber area did not differ, but focal signs of neuromuscular damage were observed in the CECS samples. At 1-year follow-up after fasciotomy, the fiber area and the number of fibers containing developmental myosin heavy chains were increased, but no enhancement of the capillary network was detected. Thus, morphologically, patients with CECS seemed to have reduced microcirculation capacity. Fasciotomy appeared to trigger a regenerative response in the muscle, however, without any increase in the capillary bed.

  • 10.
    Eriksson, Anders
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Kadi, F
    Tabatabai, P
    Bonnerud, P
    Thornell, L-E
    Anabolic steroids withdrawal in strength trained athletes: how does it affect skeletal musclesManuskript (Annet vitenskapelig)
  • 11.
    Eriksson, Anders
    et al.
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Kadi, Fawzi
    Malm, Christer
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Skeletal muscle morphology in power-lifters with and without anabolic steroids.2005Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 124, nr 2, s. 167-175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The morphological appearance of the vastus lateralis (VL) muscle from high-level power-lifters on long-term anabolic steroid supplementation (PAS) and power-lifters never taking anabolic steroids (P) was compared. The effects of long- and short-term supplementation were compared. Enzyme-immunohistochemical investigations were performed to assess muscle fiber type composition, fiber area, number of myonuclei per fiber, internal myonuclei, myonuclear domains and proportion of satellite cells. The PAS group had larger type I, IIA, IIAB and IIC fiber areas (p<0.05). The number of myonuclei/fiber and the proportion of central nuclei were significantly higher in the PAS group (p<0.05). Similar results were seen in the trapezius muscle (T) but additionally, in T the proportion of fibers expressing developmental myosin isoforms was higher in the PAS group compared to the P group. Further, in VL, the PAS group had significantly larger nuclear domains in fibers containing > or = 5 myonuclei. The results of AS on VL morphology in this study were similar to previously reported short-term effects of AS on VL. The initial effects from AS appear to be maintained for several years.

  • 12.
    Eriksson, Anders
    et al.
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Lindström, Mona
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Carlsson, Lena
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Hypertrophic muscle fibers with fissures in power-lifters; fiber splitting or defect regeneration?2006Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 126, nr 4, s. 409-417Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Power-lifters have hypertrophic muscle fibers with fissures seen in cross-sections, called as fiber splitting.Whether this phenomenon is due to real splitting or defective regeneration has not been settled. To elucidate this matter,we have examined biopsies from the trapezius and vastus lateralis of power lifters (P group) and power lifters self-administrating anabolic steroids (PAS group). For this purpose, immunohistochemical staining of serial cross -sections was used. The PAS group had significantly more fibers with fissures than the P group in the vastus lateralis (1.2%+/-0.95% vs 0.35+/-0.34, P < 0.05) but not in the trapezius muscle (1.7% in both groups). Serial sections revealed that the fibers with fissures changed their profile profoundly over short distances. Some such fibers had a mature staining profile, whereas other fibers indicated recent degeneration and/or regeneration. Activation of satellite cells and formation of aberrant segments were also evident. We conclude that the so-called split fibers are due to defect regeneration. Some fibers with fissures are the results of old events of segmental muscle fiber damage, whereas the others reflect an ongoing process. The normal regenerative process is most likely disturbed in power-lifters by their continuous training with repeated high mechanical stress on the muscles.

  • 13.
    Kadi, F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Ahlgren, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Waling, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Sundelin, Gunnevi
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    The effects of different training programs on the trapezius muscle of women with work-related neck and shoulder myalgia2000Inngår i: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 100, nr 3, s. 253-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to examine the effects of training on the structural characteristics of the trapezius muscle in women with work-related trapezius myalgia. Muscle biopsies were taken before and after 10 weeks of three different training programs (strength, endurance and coordination). Enzyme-immunohistochemical analysis was performed to assess muscle fibre types, fibre area, capillary supply and cytochrome c oxidase (COX) activity. There was an increase in the proportion of type IIA fibres in strength trained group (P < 0.05). Strength training elicited a preferential increase in the area of type II fibres (P < 0.05); both strength and endurance programs induced an increase in the number of capillaries around type I and IIA muscle fibres. Finally, all training programs induced a decrease in the proportion of COX-negative fibres. In conclusion, the trapezius muscle of women with neck and shoulder myalgia is characterised by a great potential of adaptation to physical exercise over a period of 10 weeks. The significant changes in the number of capillaries and the specific changes induced by training at the level of muscle fibres might well explain the improvement of muscle function.

  • 14.
    Kadi, F
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Concomitant increases in myonuclear and satellite cell content in female trapezius muscle following strength training.2000Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 113, nr 2, s. 99-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A skeletal muscle fibre maintains its cytoplasmic volume by means of hundreds of myonuclei distributed along its entire length. Therefore it is hypothesised that changes in fibre size would involve modifications in myonuclear number. In this study, we have examined whether 10 weeks of strength training can induce changes in the number of myonuclei and satellite cells in female trapezius muscles. Biopsies were taken pre- and posttraining from the upper part of the descending trapezius muscle of nine subjects. Muscle samples were analysed for fibre area and myonuclear and satellite cell number using immunohistochemistry. There was a 36% increase in the cross-sectional area of muscle fibres. The hypertrophy of muscle fibres was accompanied by an approximately 70% increase in myonuclear number and a 46% increase in the number of satellite cells. Myonuclei number was positively correlated to satellite cell number indicating that a muscle with an increased concentration of myonuclei will contain a correspondingly higher number of satellite cells. The acquisition of additional myonuclei appears to be required to support the enlargement of multinucleated muscle cells following 10 weeks of strength training. Increased satellite cell content suggests that mitotic divisions of satellite cells produced daughter cells that became satellite cells.

  • 15.
    Kadi, Fawzi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Bonnerud, P
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Eriksson, A
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    The expression of androgen receptors in human neck and limb muscles: effects of training and self-administration of androgenic-anabolic steroids2000Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 113, nr 1, s. 25-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of this study was to investigate the immunohistochemical expression of androgen receptors (AR) in human vastus lateralis and trapezius muscles and to determine whether long-term strength training and self-administration of androgenic-anabolic steroids are accompanied by changes in AR content. Biopsy samples were taken from eight high-level power-lifters (P), nine high-level power-lifters who used anabolic steroids (PAS) and six untrained subjects (U). Myonuclei and AR were visualised in cross-sections stained with the monoclonal antibody against AR and 4',6-diamidino-2-phenylindole. The proportion of AR-containing myonuclei per fibre cross-section was higher in the trapezius than in the vastus lateralis (P<0.05). In the trapezius, the proportion of AR-containing myonuclei was higher in P compared to U and in PAS compared to both P and U (P<0. 05). On the contrary, in the vastus lateralis, there were no differences in AR content between the three groups. Myonuclear number in both muscles was higher in P compared to U and in PAS compared to both P and U (P<0.05). In conclusion, AR content differs greatly between human neck and limb muscles. Moreover, the regulation of AR-containing myonuclei following training and self-administration of androgenic-anabolic steroids is muscle dependent.

  • 16.
    Kadi, Fawzi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Eriksson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Butler-Browne, GS
    Thornell, L-E
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Cellular adaptation of the trapezius muscle in strength-trained athletes1999Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 111, nr 3, s. 189-195Artikkel i tidsskrift (Fagfellevurdert)
  • 17.
    Kadi, Fawzi
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Eriksson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Holmner, S
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Effects of anabolic steroids on the muscle cells of strength trained athletes1999Inngår i: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 31, nr 11, s. 1528-1534Artikkel i tidsskrift (Fagfellevurdert)
  • 18.
    Kjellgren, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Ryan, Michelle
    Ohlendieck, Kay
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Sarco(endo)plasmic reticulum ca2+ATPases (SERCA1 and 2) in human extraocular muscles2003Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, nr 12, s. 5057-5062Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To investigate the composition of the fibers in human extraocular muscles (EOMs) with respect to the sarco(endo)plasmic reticulum Ca(2+)ATPases (SERCA)-1 and -2 and to investigate possible correlations between SERCA and myosin heavy chain (MyHC) composition. METHODS: EOM samples were processed for immunocytochemistry with monoclonal antibodies specific against SERCA1 (fast isoform), SERCA2 (slow isoform), or different MyHCs. A total of 1571 fibers were analyzed. Microsomal EOM fractions were analyzed with SDS-PAGE and immunoblots. RESULTS: The fast fibers, containing MyHCIIa, accounted for 79% of the fibers in the orbital layer (OL) and 74% in the global layer (GL). More than 99% of these fibers contained SERCA1, and 86% of them coexpressed SERCA1 and -2. Almost all slow fibers stained with SERCA2; 54% of those in the GL and all in the OL coexpressed SERCA1 and -2. Fifteen percent of the fibers in the GL and less than 1% in the OL were MyHCeom(pos)/MyHCIIa(neg) fibers. All these contained SERCA1 and in the OL also stained strongly with anti-SERCA2. Biochemically SERCA2 was more abundant than SERCA1. CONCLUSIONS: The human EOMs had a very complex pattern of expression of the major protein regulating fiber relaxation rate. The coexistence of SERCA1 and -2, together with complex mixtures of MyHCs in most of the fibers provide the human EOMs with a unique molecular portfolio that allows a highly specific fine-tuning regimen of contraction and relaxation.

  • 19.
    Kjellgren, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Andersen, Jesper
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Myosin heavy chain isoforms in human extraocular muscle2003Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 44, nr 4, s. 1419-1425Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To investigate the myosin heavy chain (MyHC) composition of human extraocular (EOM) and levator palpebrae (LP) muscle fibers. METHODS: Adult human EOMs and LP were studied with SDS-PAGE, immunoblots, and immunocytochemistry, with antibodies against six MyHC isoforms. Myofibrillar adenosine triphosphatase (mATPase) and reduced nicotinamide adenine dinucleotide (NADH)-TR activity and fiber area were also determined. RESULTS: Most of the fibers in both layers stained strongly with anti-MyHCIIa. Approximately 14% of the fibers in the global layer and 16% in the orbital layer were labeled with anti-MyHCI. The remaining 24% of the fibers in the global layer and 3% in the orbital layer were not stained with either of these two antibodies, but were reactive to anti-MyHCeom (MyHCeom(pos)/MyHCIIa(neg) fibers). The fibers stained with anti-MyHCI had acid-stable mATPase activity, and the remainder of the fibers had alkaline-stable mATPase activity. Almost all the slow fibers stained with both anti-MyHCI and anti-MyHCslow tonic in both layers. Anti-MyHCalpha-cardiac stained approximately 26% of these slow fibers in the orbital layer and 7% in the global layer. Some slow fibers in both layers lacked staining with anti-MyHCslow tonic or with anti-MyHCalpha-cardiac. MyHCemb and/or MyHCeom were also present in some of the fibers of all the groups. The LP did not stain with anti-MyHCslow tonic. CONCLUSIONS: The present study revealed that the human EOMs have a very complex fiber type and MyHC composition and differ significantly from the EOMs of other species. The features of the LP were distinct from those of the four recti, the obliquus superior, and the limb muscles.

  • 20.
    Kjellgren, Daniel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Virtanen, Ismo
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Laminin isoforms in human extraocular muscles2004Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 45, nr 12, s. 4233-4239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To determine the laminin isoform composition of the basement membranes (BMs) in the human extraocular muscles (EOMs) and relate it to the fact that EOMs are spared in laminin alpha2-chain-deficient congenital muscular dystrophy. METHODS: Samples from adult human EOMs and limb muscle were processed for immunocytochemistry, with monoclonal antibodies against laminin chains (Ln) alpha1 to -5, beta1 and -2, and gamma1. Neuromuscular junctions (NMJs) were identified with acetylcholinesterase reaction. The capillary density was measured in sections stained with anti-Lnalpha5. RESULTS: The extrasynaptic BM of the EOM muscle fibers contained Lnalpha2, -beta1, -beta2, and -gamma1, and, in contrast to limb muscle, it also contained Lnalpha4 and -alpha5, to some extent. The distinct laminin composition of the EOMs was confirmed by the presence of Lutheran protein, an alpha5-chain-specific receptor not found in limb muscle. At the NMJs, there was increased expression of Lnalpha4 and expression of Lnalpha2, -alpha5, -beta1, -beta2, and -gamma1 was also maintained. The capillary density was very high (1050 +/- 190 capillaries/mm(2)) in the EOMs and significantly (P < 0.05) higher in the orbital (1170 +/- 180 capillaries/mm(2)) than in the global (930 +/- 110 capillaries/mm(2)) layer. CONCLUSIONS: The human EOMs showed important differences in laminin isoform composition and capillary density when compared with human limb muscle and muscles of other species. The presence of additional laminin isoforms other than laminin-2 in the BM of the extrasynaptic sarcolemma could partly explain the sparing of the EOMs in Lnalpha2-deficient congenital muscular dystrophy.

  • 21.
    Lindström, Mona
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Satellite cell heterogeneity with respect to expression of MyoD, myogenin, Dlk1 and c-Met in human skeletal muscle: application to a cohort of power lifters and sedentary men2010Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 134, nr 4, s. 371-385Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human satellite cells (SCs) are heterogeneous with respect to markers for their identification in the niche between the muscle fibre plasma membrane and its basal lamina. We have previously shown that, in biopsies from highly competitive power lifters, power lifters with long-term use of anabolic steroids and a population of healthy sedentary men, antibodies against the neuronal cell adhesion molecule (NCAM) and the paired box transcription factor Pax7 together label 94% of the SCs, NCAM alone labels 4% and Pax7 alone labels 1%. In the present study, we have further studied these biopsies with four markers related to SC activation and differentiation. Our study unequivocally shows that staining for MyoD and myogenin are present in nuclei of SCs and of myoblasts and myotubes in areas of muscle fibre regeneration. Staining for c-Met was observed in a proportion of Pax7+ SCs. However, widespread labelling of the sarcolemma precluded the quantification of c-Met+/Pax7+ SCs and the use of c-Met as a reliable SC marker. Pax7+ SCs labelled by anti-Delta like1 (Dlk1) were present in all samples but in variable proportions, whereas muscle progenitor cells related to repair were Dlk1⁻. Staining for Dlk1 was also observed in Pax7⁻ interstitial cells and in the cytoplasm of some small muscle fibres. Interestingly, the proportion of Dlk1+/Pax7+ SCs was significantly different between the groups of power lifters. Thus, our study confirms that human SCs show marked heterogeneity and this is discussed in terms of SC activation, myonuclei turnover, muscle fibre growth and muscle fibre damage and repair.

  • 22.
    Lindström, Mona
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    New multiple labelling method for improved satellite cell identification in human muscle: application to a cohort of power-lifters and sedentary men.2009Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 132, nr 2, s. 141-57Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Presently applied methods to identify and quantify human satellite cells (SCs) give discrepant results. We introduce a new immunofluorescence method that simultaneously monitors two SC markers (NCAM and Pax7), the basal lamina and nuclei. Biopsies from power-lifters, power-lifters using anabolic substances and untrained subjects were re-examined. Significantly different results from those with staining for NCAM and nuclei were observed. There were three subtypes of SCs; NCAM(+)/Pax7(+) (94%), NCAM(+)/Pax7(-) (4%) and NCAM(-)/Pax7(+) (1%) but large individual variability existed. The proportion of SCs per nuclei within the basal lamina of myofibres (SC/N) was similar for all groups reflecting a balance between the number of SCs and myonuclei to maintain homeostasis. We emphasise that it is important to quantify both SC/N and the number of SCs per fibre. Our multiple marker method is more reliable for SC identification and quantification and can be used to evaluate other markers of muscle progenitor cells.

  • 23.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Eriksson, Per-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Klinisk oral fysiologi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Fiber content and myosin heavy chain composition of muscle spindles in aged human biceps brachii2005Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 53, nr 4, s. 445-454Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The present study investigated potential age-related changes in human muscle spindles with respect to the intrafusal fiber-type content and myosin heavy chain (MyHC) composition in biceps brachii muscle. The total number of intrafusal fibers per spindle decreased significantly with aging, due to a significant reduction in the number of nuclear chain fibers. Nuclear chain fibers in old spindles were short and some showed novel expression of MyHC alpha-cardiac. The expression of MyHC alpha-cardiac in bag1 and bag2 fibers was greatly decreased in the A region. The expression of slow MyHC was increased in nuclear bag1 fibers and that of fetal MyHC decreased in bag2 fibers whereas the patterns of distribution of the remaining MyHC isoforms were generally not affected by aging. We conclude that aging appears to have an important impact on muscle spindle composition. These changes in muscle spindle phenotype may reflect an age-related deterioration in sensory and motor innervation and are likely to have an impact in motor control in the elderly.

  • 24.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Eriksson, Per-Olof
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Myosin heavy chain composition of muscle spindles in human biceps brachii2002Inngår i: Histochem Cell Biol, Vol. 50, nr 2, s. 171-184Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Data on the myosin heavy chain (MyHC) composition of human muscle spindles are scarce in spite of the well-known correlation between MyHC composition and functional properties of skeletal muscle fibers. The MyHC composition of intrafusal fibers from 36 spindles of human biceps brachii muscle was studied in detail by immunocytochemistry with a large battery of antibodies. The MyHC content of isolated muscle spindles was assessed with SDS-PAGE and immunoblots. Four major MyHC isoforms (MyHCI, IIa, embryonic, and intrafusal) were detected with SDS-PAGE. Immunocytochemistry revealed very complex staining patterns for each intrafusal fiber type. The bag(1) fibers contained slow tonic MyHC along their entire fiber length and MyHCI, alpha-cardiac, embryonic, and fetal isoforms along a variable part of their length. The bag(2) fibers contained MyHC slow tonic, I, alpha-cardiac, embryonic, and fetal isoforms with regional variations. Chain fibers contained MyHCIIa, embryonic, and fetal isoforms throughout the fiber, and MyHCIIx at least in the juxtaequatorial region. Virtually each muscle spindle had a different allotment of numbers of bag(1), bag(2) and chain fibers. Taken together, the complexity in intrafusal fiber content and MyHC composition observed indicate that each muscle spindle in the human biceps has a unique identity.

  • 25.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Distribution of SERCA isoforms in human intrafusal fibers2003Inngår i: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 120, nr 4, s. 299-306Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) is a membrane protein that plays a crucial role in muscle relaxation by transporting cytosolic Ca2+ into the lumen of the sarco/endoplasmic reticulum. In this study, the presence of SERCA1 and SERCA2 was investigated in human intrafusal fibers by immunocytochemistry. Nuclear bag1 fibers contained both SERCA1 and SERCA2 isoforms, with predominant staining seen with SERCA2 in the A and B regions. Most nuclear bag2 fibers also contained SERCA1 and SERCA2 isoforms and their coexistence frequently occurred in the A region. SERCA1 was present whereas SERCA2 was generally absent in the nuclear chain fibers. The staining intensity seen with the SERCA1 monoclonal antibody varied in the order of chain>bag1>bag2. The expression of SERCA1 isoform was found to correlate with the presence of fast myosin heavy chain (MyHC) isoform in nuclear chain fibers, whereas for nuclear bag fibers there was no such apparent correlation between patterns of expression of SERCA and MyHC isoforms. The phenotype revealed for the human bag fibers was very sophisticated and adapted to attain a very wide range of contraction and relaxation velocities.

  • 26.
    Liu, Jing-Xia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Muscle spindles in the deep muscles of the human neck: a morphological and immunocytochemical study2003Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 51, nr 2, s. 175-186Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Muscle spindle density is extremely high in the deep muscles of the human neck. However, there is a paucity of information regarding the morphology and immunoreactivity of these muscle spindles. The objective of this study was to investigate the intrafusal fiber content and to assess the myosin heavy chain (MyHC) composition of muscle spindles from human deep neck muscles. In addition to the conventional spindles containing bag(1), bag(2), and chain fibers (b(1)b(2)c spindle), we observed a number of spindles lacking bag(1) (b(2)c spindle) or bag(2) (b(1)c spindle) fibers. Both bag(1) and bag(2) fibers contained slow tonic MyHCs along their entire fiber length and MyHCI, MyHCIIa, embryonic, and alpha-cardiac MyHC isoforms along a variable length of the fibers. Fetal MyHC was present in bag(2) fibers but not in bag(1) fibers. Nuclear chain fibers contained MyHCIIa, embryonic, and fetal isoforms with regional variations. We also compared the present data with our previous results obtained from muscle spindles in human biceps brachii and the first lumbrical muscles. The allotment of numbers of intrafusal fibers and the MyHC composition showed some muscle-related differences, suggesting functional specialization in the control of movement among different human muscles.

  • 27.
    Monemi, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Liu, Jingxia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Eriksson, Per-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Myosin heavy chain composition of the human lateral pterygoid and digastric muscles in young adults and elderly.2000Inngår i: Journal of Muscle Research and Cell Motility, ISSN 0142-4319, E-ISSN 1573-2657, Vol. 21, nr 4, s. 303-312Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The myosin heavy chain (MyHC) content in different parts of, two jaw opening muscle, the human lateral pterygoid and the digastric muscles of five young adult and five elderly subjects (mean age 22 and 73 years, respectively) was determined, using gel electrophoresis and immunohistochemical methods. The lateral pterygoid of both young and elderly contained predominantly slow MyHC, and fast A MyHC was the major fast isoform. In contrast, the digastric was composed of slow, fast A and fast X MyHCs in about equal proportions in both age groups. About half of the lateral pterygoid fibres contained mixtures of slow and fast MyHCs, often together with alpha-cardiac MyHC. In the digastric, co-existence of slow and fast MyHCs was rare, and alpha-cardiac MyHC was lacking. On the other hand, co-expression of fast A and fast X MyHCs was found more often in the digastric than in the lateral pterygoid. In both age groups about half of the digastric IIB fibres contained solely fast X MyHC. In the lateral pterygoid, type IIB fibres with pure fast X MyHC was found in only one subject. The lateral pterygoid in elderly showed a significant amount of fibres with solely fast A MyHC, which were occasionally found in young adults. In the digastric, no significant differences were found between young and elderly, although the muscles of elderly contained lower mean value of slow MyHC, as compared to that of young muscles. It is concluded that the lateral pterygoid and the digastric muscles differ not only in the MyHC composition but also in modifications of the MyHC phenotypes during aging, suggesting that they have separate roles in jaw opening function.

  • 28. Necking, Lars E
    et al.
    Lundborg, Göran
    Lundström, Ronnie
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Thornell, Lars-Eric
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Fridén, Jan
    Hand muscle pathology after long-term vibration exposure.2004Inngår i: Journal of Hand Surgery-British and European volume, ISSN 0266-7681, Vol. 29, nr 5, s. 431-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The morphology of the abductor pollicis brevis muscle was studied in 20 patients suffering from hand-arm vibration syndrome. The main morphological changes observed were centrally located myonuclei and fibre type grouping (found in all 20 muscle biopsies), angulated muscle fibres (found in 19 biopsies), ring fibres and regenerating fibres (found in 18 biopsies) and fibrosis (found in 17 biopsies). The observed abnormalities are believed to reflect damage to both the muscle fibres and the motor nerve. The changes were related to different vibration exposure parameters. The number of fibres demonstrating centrally located nuclei correlated significantly with the cumulative vibration exposure, while the number of angulated fibres correlated significantly with the total vibration exposure time. This indicates that the vibrating tools may cause direct damage to muscle fibres as well as nerves.

  • 29.
    Nordin, Angelica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Larsson, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Holmberg, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Tissue-specific splicing of ISCU results in a skeletal muscle phenotype in myopathy with lactic acidosis, while complete loss of ISCU results in early embryonic death in mice2011Inngår i: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 129, nr 4, s. 371-378Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hereditary myopathy with lactic acidosis (HML) is caused by an intron mutation in the iron-sulphur cluster assembly gene (ISCU) leading to incorporation of intron sequence into the mRNA. This results in a deficiency of Fe-S cluster proteins, affecting the TCA cycle and the respiratory chain. The proteins involved in the Fe-S machinery are evolutionary conserved and shown to be fundamental in all organisms examined. ISCU is expressed at high levels in numerous tissues in mammals, including high metabolic tissues like the heart, suggesting that a drastic mutation in the ISCU gene would be damaging to all energy-demanding organs. In spite of this, the symptoms in patients with HML are restricted to skeletal muscle, and it has been proposed that splicing events may contribute to the muscle specificity. In this study we confirm that a striking difference in the splicing pattern of mutant ISCU exists between different tissues. The highest level of incorrectly spliced ISCU mRNA was found in skeletal muscle, while the normal splice form predominated in patient heart. The splicing differences were also reflected at a functional level, where loss of Fe-S cluster carrying enzymes and accumulation of iron were present in muscle, but absent in other tissues. We also show that complete loss of ISCU in mice results in early embryonic death. The mice data confirm a fundamental role for ISCU in mammals and further support tissue-specific splicing as the major mechanism limiting the phenotype to skeletal muscle in HML.

  • 30. Oldfors, Anders
    et al.
    Tajsharghi, H
    Thornell, Lars-Eric
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Mutation of the slow myosin heavy chain rod domain underlies hyaline body myopathy.2005Inngår i: Neurology, ISSN 1526-632X, Vol. 64, nr 3, s. 580-1; author reply 580Artikkel i tidsskrift (Annet vitenskapelig)
  • 31.
    Olsson, Angelica
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Lind, Lisbet
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Holmberg, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect2008Inngår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 17, nr 11, s. 1666-1672Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We describe the mapping and identification of the gene for hereditary myopathy with lactic acidosis (HML). HML is characterized by low physical performance, resulting in physical exertion that causes early exhaustion, dyspnoea and palpitations. Using an autosomal recessive mode of inheritance, we mapped the trait to chromosome 12q23.3-24.11, with a maximum lod score of 5.26. The 1.6-Mb disease-critical region contained one obvious candidate gene-ISCU-specifying a protein involved in iron-sulphur cluster assembly. IscU is produced in two isoforms; one cytosolic and one mitochondrial, coded for by different splice variants of the ISCU gene. Mutational analysis of all exon and intron sequences as well as 1000 bp of the promoter of the ISCU gene revealed one intron mutation that was specific for the disease haplotype. The mutation is located in a region with homology to the interferon-stimulated response element (ISRE), but we could not see any effect of the mutation on expression levels in vitro or in vivo. We did, however, observe a drastic difference in the splicing pattern between patients and controls. In controls the mRNA was, as expected, mainly in the mitochondrial form, while in the patients a larger mRNA transcript was predominant. Sequencing of the product revealed that the mutation activates cryptic splice sites in intron 5 resulting in aberrant mRNA containing 100 bp of the intron. To conclude, our data strongly suggest that an intron mutation in the ISCU gene, leading to incorrectly spliced mRNA, is the cause of myopathy with lactic acidosis in this family.

  • 32. Otonkoski, T
    et al.
    Banerjee, M
    Korsgren, O
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Virtanen, Ismo
    Unique basement membrane structure of human pancreatic islets: implications for beta-cell growth and differentiation.2008Inngår i: Diabetes, obesity & metabolism, ISSN 1463-1326, Vol. 10 Suppl 4, s. 119-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Basement membranes (BMs) are an important part of the physiological microenvironment of pancreatic islet cells. In mouse islets, beta-cells interact directly with BMs of capillary endothelial cells. We have shown that in the human islets, the capillaries are surrounded by a double BM both in foetal and adult tissues. The endocrine islet cells are facing a BM that is separate from the endothelia. Laminins are the functionally most important component of BMs. The only laminin isoform present in the human endocrine islet BM is laminin-511 (previously known as laminin 10). The islet cells facing this BM have a strong and polarized expression of Lutheran glycoprotein, which is a well-known receptor for the laminin alpha 5 chain. Dispersed human islet cells adhere to purified human laminin-511 and the binding is equally effectively blocked by a soluble form of Lutheran as by antibody against integrin beta1. Our results reveal unique features of the BM structure of human islets, different from rodents. This information has potentially important implications for the generation of an optimal microenvironment for beta-cell function, proliferation and differentiation.

  • 33.
    Pedrosa-Domellöf, Fatima
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Department of Musculoskeletal Research, National Institute for Working Life, Umeå, Sweden.
    Holmgren, Ylva
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lucas, C A
    University of Sydney.
    Hoh, J F
    University of Sydney.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Department of Musculoskeletal Research, National Institute for Working Life, Umeå, Sweden.
    Human extraocular muscles: unique pattern of myosin heavy chain expression during myotube formation2000Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 41, nr 7, s. 1608-1616Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To study the myosin heavy chain composition of the human extraocular muscles (EOMs) during development.

    METHODS: EOMs from human fetuses of 8 to 22 weeks of gestation were studied with immunocytochemistry and gel electrophoresis. Antibodies specific against nine isoforms of myosin heavy chain (MyHC) were used in serial frozen sections.

    RESULTS: The developing EOMs had a delayed time course of myotube formation and a unique composition and distribution of MyHCs compared with human limb skeletal muscle. The primary myotubes coexpressed two developmental isoforms of MyHCI from the earliest stages. The third developmental MyHCI delineated the future orbital layer at 10 to 12 weeks of gestation. MyHC-slow tonic also appeared early, whereas MyHC alpha-cardiac and MyHC-extraocular, important components of adult EOM, were never detected at the gestational ages studied.

    CONCLUSIONS: The developmental features of the EOMs differed significantly from those reported for limb muscles of the corresponding ages. It is clear that the knowledge of limb muscle development does not fully apply to more specialized muscles, such as the eye muscles. The extreme complexity displayed by the EOMs probably reflects their distinct embryonic origin, innervation, and regulatory program of myogenesis.

  • 34.
    Pedrosa-Domellöf, Fatima
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Tiger, C F
    Department of Cell & Molecular Biology, Uppsala University, Uppsala.
    Virtanen, I
    Department of Anatomy, Institute of Biomedicine, University of Helsinki, Helsinki.
    Thornell, L E
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Gullberg, D
    Department of Cell & Molecular Biology, Uppsala University, Uppsala.
    Laminin chains in developing and adult human myotendinous junctions.2000Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 48, nr 2, s. 201-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In addition to being the specialized site for transmission of force from the muscle to the tendon, the myotendinous junction (MTJ) also plays an important role in muscle splitting during morphogenesis. An early event in the formation of the MTJ is a regional deposition of basement membranes. We used immunocytochemistry to investigate the distribution of laminin chains during the development of MTJs in human limb muscle at 8-22 weeks of gestation (wg) and in adult MTJs. We used polyclonal antibodies and a new monoclonal antibody (MAb) against the human laminin alpha1 G4/G5 domains. At 8-10 wg, laminin alpha1 and laminin alpha5 chains were specifically localized to the MTJ. Laminin alpha1 chain remained restricted to the MTJ at 22 wg as the laminin beta2 chain had appeared, whereas the laminin alpha5 chain became deposited along the entire length of the myotubes from 12 wg. In the adult MTJ, only vestigial amounts of laminin alpha1 and laminin alpha5 chains could be detected. On the basis of co-distribution data, we speculate that laminin alpha1 chain in the forming MTJ undergoes an isoform switch from laminin 1 to laminin 3. Our data indicate a potentially important role for laminin alpha1 chain in skeletal muscle formation.

  • 35.
    Petäjäniemi, Noora
    et al.
    University of Helsinki.
    Korhonen, Matti
    Helsinki University Central Hospital.
    Kortesmaa, Jarkko
    Karolinska Institute and BioStratum AB, Stockholm.
    Tryggvason, Karl
    Karolinska Institute.
    Sekiguchi, Kiyotoshi
    Osaka University.
    Fujiwara, Hironobu
    Osaka University.
    Sorokin, Lydia
    IZKF Nachwuchsgruppe II, Nikolaus Fiebiger Center, Erlangen, Germany.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wondimu, Zenebech
    Karolinska Institute.
    Assefa, Daniel
    Karolinska Institute.
    Patarroyo, Manuel
    Karolinska Institute.
    Virtanen, Ismo
    University of Helsinki.
    Localization of laminin alpha4-chain in developing and adult human tissues2002Inngår i: Journal of Histochemistry and Cytochemistry, ISSN 0022-1554, E-ISSN 1551-5044, Vol. 50, nr 8, s. 1113-1130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent studies suggest important functions for laminin-8 (Ln-8; alpha4beta1gamma1) in vascular and blood cell biology, but its distribution in human tissues has remained elusive. We have raised a monoclonal antibody (MAb) FC10, and by enzyme-linked immunoassay (EIA) and Western blotting techniques we show that it recognizes the human Ln alpha4-chain. Immunoreactivity for the Ln alpha4-chain was localized in tissues of mesodermal origin, such as basement membranes (BMs) of endothelia, adipocytes, and skeletal, smooth, and cardiac muscle cells. In addition, the Ln alpha4-chain was found in regions of some epithelial BMs, including epidermis, salivary glands, pancreas, esophageal and gastric glands, intestinal crypts, and some renal medullary tubules. Developmental differences in the distribution of Ln alpha4-chain were detected in skeletal muscle, walls of vessels, and intestinal crypts. Ln alpha4- and Ln alpha2-chains co-localized in BMs of fetal skeletal muscle cells and in some epithelial BMs, e.g., in gastric glands and acini of pancreas. Cultured human pulmonary artery endothelial (HPAE) cells produced Ln alpha4-chain as M(r) 180,000 and 200,000 doublet and rapidly deposited it to the growth substratum. In cell-free extracellular matrices of human kidney and lung, Ln alpha4-chain was found as M(r) 180,000 protein.

  • 36.
    Pontén, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Department of Paediatric Orthopaedics, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm.
    Fridén, Jan
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lieber, Richard L.
    Spastic wrist flexors are more severely affected than wrist extensors in children with cerebral palsy2007Inngår i: Developmental Medicine & Child Neurology, ISSN 0012-1622, E-ISSN 1469-8749, Vol. 47, nr 6, s. 384-389Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Morphological properties of skeletal muscle were compared between wrist flexors and extensors within the same children (n = 8, six females, two males; age range 4 to 9y, median age 7 y) with wrist muscle imbalance secondary to spastic cerebral palsy (CP). Five patients had hemiplegic CP, two diplegic CP, and one patient had tetraplegic CP. Muscle biopsies were taken during either tendon transfer or tendon lengthening procedures. Analyses included distribution of muscle fibre types, fibre sizes, and expression of developmental myosins. Extensor fibre area was significantly greater than flexor fibre area for type 2A fibres and type 2B fibres but not for type 1 fibres. Coefficient of variation (CV) of fibre size for all three fibre types was greater for flexors compared with extensors. The greatest CV was observed for the type 2A fibres in flexors (39.5 [3.6%]). A wide variation was observed for expression of developmental myosin with the magnitude of the expression being greater, but not statistically significant, in flexors compared with extensors (5.4/mm2 vs 0.53/mm2). These data demonstrate that significant secondary myopathy of wrist flexor muscles results from CP.

  • 37. Périé, Sophie
    et al.
    Mamchaoui, Kamel
    Mouly, Vincent
    Blot, Stéphane
    Bouazza, Belaïd
    Thornell, Lars-Eric
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    St Guily, Jean Lacau
    Butler-Browne, Gillian
    Premature proliferative arrest of cricopharyngeal myoblasts in oculo-pharyngeal muscular dystrophy: Therapeutic perspectives of autologous myoblast transplantation.2006Inngår i: Neuromuscular Disorders, ISSN 0960-8966, Vol. 16, nr 11, s. 770-81Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cultures of myoblasts isolated from cricopharyngeal muscles from patients with oculopharyngeal muscular dystrophy (OPMD) have been performed to study the effect of the expanded (GCG)8-13 repeat, located on the poly(A) binding protein nuclear-1 (PABPN1), on satellite cell phenotype. Cell cultures exhibited a reduced myogenicity, as well as a rapid decrease in proliferative lifespan, as compared to controls. The incorporation of BrdU decreased during the proliferative lifespan, due to a progressive accumulation of non-dividing cells. A lower fusion index was also observed, but myoblasts were able to form large myotubes when OPMD cultures were purified, although a rapid loss of myogenicity during successive passages was also observed. Myoblasts isolated from unaffected muscles did not show the defects observed in cricopharyngeal muscle cultures. The PABPN1 was predominantly located in nuclei of myoblasts and in both the nuclei and cytoplasm of myotubes in OPMD cultures. In vivo analysis of OPMD muscles showed that the number of satellite cells was slightly higher than that observed in age matched controls. Mutation of the PABPN1 in OPMD provokes premature senescence in dividing myoblasts, that may be due to intranuclear toxic aggregates. These results suggest that myoblast autografts, isolated from unaffected muscles, and injected into the dystrophic pharyngeal muscles, may be a useful therapeutic strategy to restore muscular function. Its tolerance and feasibility has been preclinically demonstrated in the dog.

  • 38.
    Rae, Dale E
    et al.
    University of Cape Town.
    Vignaud, Alban
    Institut de Myologie, INSERM, Paris.
    Butler-Browne, Gillian S
    Institut de Myologie, INSERM, Paris.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Sinclair-Smith, Colin
    Red Cross Children’s Hospital, Cape Town.
    Derman, E Wayne
    University of Cape Town.
    Lambert, Mike I
    University of Cape Town.
    Collins, Malcolm
    University of Cape Town, Red Cross Children’s Hospital, Cape Town.
    Skeletal muscle telomere length in healthy, experienced, endurance runners.2010Inngår i: European journal of applied physiology, ISSN 1439-6327, Vol. 109, nr 2, s. 323-330Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum terminal restriction fragment (TRF) length in the vastus lateralis muscle of 18 experienced endurance runners (mean age: 42 +/- 7 years) to those of 19 sedentary individuals (mean age: 39 +/- 10 years). The runners had covered almost 50,000 km in training and racing over 15 years. Minimum TRF lengths measured in the muscle of both groups were similar (P = 0.805) and within the normal range. Minimum TRF length in the runners, however, was inversely related to their years spent running (r = -0.63, P = 0.007) and hours spent training (r = -0.52, P = 0.035). Therefore, since exposure to endurance running may influence minimum TRF length, and by implication, the proliferative potential of the satellite cells, chronic endurance running may be seen as a stressor to skeletal muscle.

  • 39.
    Renault, Valérie
    et al.
    CNRS UMR 7000, Cytosquelette et Développement, Faculté de Medécine Pitié-Salpétrière, 105 Blvd. de l'Hôpital, F-75634 Paris, France.
    Rolland, Eric
    Département de Chirurgie Orthopédique, Hôpital de la Pitié-Salpétrière, F-75641 Paris, France.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Mouly, Vincent
    CNRS UMR 7000, Cytosquelette et Développement, Faculté de Medécine Pitié-Salpétrière, 105 Blvd. de l'Hôpital, F-75634 Paris, France.
    Butler-Browne, Gillian
    CNRS UMR 7000, Cytosquelette et Développement, Faculté de Medécine Pitié-Salpétrière, 105 Blvd. de l'Hôpital, F-75634 Paris, France.
    Distribution of satellite cells in the human vastus lateralis muscle during aging2002Inngår i: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 37, nr 12, s. 1513-1514, Article Number: PII S0531-5565(02)00095-5Artikkel i tidsskrift (Fagfellevurdert)
  • 40.
    Renault, Valérie
    et al.
    UMR CNRS 7000, Cytosquelette et Développement, Faculté de Medecine Pitié-Salpétrière, 105, bd de l'Hôpital, F-75634 Paris Cedex 13, France.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Butler-Browne, Gillian
    UMR CNRS 7000, Cytosquelette et Développement, Faculté de Medecine Pitié-Salpétrière, 105, bd de l'Hôpital, F-75634 Paris Cedex 13, France.
    Mouly, Vincent
    UMR CNRS 7000, Cytosquelette et Développement, Faculté de Medecine Pitié-Salpétrière, 105, bd de l'Hôpital, F-75634 Paris Cedex 13, France.
    Human skeletal muscle satellite cells: aging, oxidative stress and the mitotic clock2002Inngår i: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 37, nr 10-11, s. 1229-1236, Article Number: PII S0531-5565(02)00129-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Normal satellite cell cultures, isolated from human skeletal muscle, have a limited proliferative capacity and inevitably reach replicative senescence. In this study, we have focused on the consequences of a single oxidative stress by hydrogen peroxide (H(2)O(2)) on both proliferative capacity and myogenic characteristics. Treatment with 1mM H(2)O(2) for 30 min causes a small decrease in the viability and lifespan while the number of cells which are able to proliferate, decreases dramatically. This premature arrest of the cells in a non-proliferative state was not due to spontaneous differentiation since there was no increase in the number of myogenin positive cells. This stress did not affect the myogenicity of the cells or their ability to differentiate and fuse to form multinucleated myotubes. In addition, the mitotic clock does not seem to be modified by oxidative stress treatment since the rate of telomere shortening was similar in H(2)O(2)-treated and control cells. This could be the consequence of the high level of oxygen consumption with an even higher level of ROS being produced in skeletal muscle than in other tissues which would be counteracted by an increase in the antioxidant defense system.

  • 41.
    Renault, Valérie
    et al.
    CNRS UMR 7000, Cytosquelette et Développement, F-75 634 Paris.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Center for Musculoskeletal Research, National Institute of Working Life, Umeå.
    Eriksson, Per-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi. Center for Musculoskeletal Research, National Institute of Working Life, Umeå.
    Butler-Browne, Gillian
    CNRS UMR 7000, Cytosquelette et Développement, F-75 634 Paris.
    Mouly, Vincent
    CNRS UMR 7000, Cytosquelette et Développement, F-75 634 Paris, France.
    Regenerative potential of human skeletal muscle during aging2002Inngår i: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 1, nr 2, s. 132-139Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study, we have investigated the consequences of aging on the regenerative capacity of human skeletal muscle by evaluating two parameters: (i) variation in telomere length which was used to evaluate the in vivo turn-over and (ii) the proportion of satellite cells calculated as compared to the total number of nuclei in a muscle fibre. Two skeletal muscles which have different types of innervation were analysed: the biceps brachii, a limb muscle, and the masseter, a masticatory muscle. The biopsies were obtained from two groups: young adults (23 +/- 1.15 years old) and aged adults (74 +/- 4.25 years old). Our results showed that during adult life, minimum telomere lengths and mean telomere lengths remained stable in the two muscles. The mean number of myonuclei per fibre was lower in the biceps brachii than in the masseter but no significant change was observed in either muscle with increasing age. However, the number of satellite cells, expressed as a proportion of myonuclei, decreased with age in both muscles. Therefore, normal aging of skeletal muscle in vivo is reflected by the number of satellite cells available for regeneration, but not by the mean number of myonuclei per fibre or by telomere lengths. We conclude that a decrease in regenerative capacity with age may be partially explained by a reduced availability of satellite cells.

  • 42. Ryan, Michelle
    et al.
    Butler-Browne, Gillian
    Erzen, Ida
    Mouly, Vincent
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wernig, Anton
    Ohlendieck, Kay
    Persistent expression of the alpha(1S)-dihydropyridine receptor in aged human skeletal muscle: Implications for the excitation-contraction uncoupling hypothesis of sarcopenia2003Inngår i: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 11, nr 4, s. 425-434Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies on aged animal muscle suggest that excitation-contraction uncoupling and fibre transitions play a central role in sarcopenia, the progressive loss and functional decline of aging skeletal muscle fibres. A drastic reduction in the voltage-sensing alpha1S-subunit of the transverse-tubular dihydropyridine receptor is believed to be the underlying cause for a decreased transmission of the surface depolarization signal into Ca2+-mediated muscle contraction. Extending these studies to human muscle, we asked whether potential changes in the relative expression of the voltage sensor occur in senescent human fibres. For internal standardization and as markers of potential fast-to-slow transitions, the fast isoforms of the Ca2+-binding element calsequestrin and the myosin heavy chain were employed. Besides small inter-individual variations in expression levels, the microsomal immunoblot analysis of vastus lateralis autopsy specimens from male humans aged 18 to 82 years of age showed no major changes in the relative abundance of the alpha1S- and alpha2-dihydropyridine receptor, fast calsequestrin and the slow/fast myosin heavy chains. The oligomeric status of the alpha1S-dihydropyridine receptor was unaltered in aged fibres. Biochemical assays revealed no significant modifications in Ca2+-ATPase activity and a reduced Ca2+-binding capacity in aged human muscle preparations. Although impairments of other Ca2+-regulatory proteins and/or disturbed protein-protein interactions might be involved in the pathophysiological changes of sarcopenia, dihydropyridine receptor and calsequestrin expression seem to be preserved during the aging process of human skeletal muscle fibres. Hence, the supposition that excitation-contraction uncoupling is responsible for sarcopenia can not be transferred from animal models to senescent human muscle without modifications.

  • 43.
    Rönnblom, Anton
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Shah, Farhan K.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Tano, Krister
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Unique fiber phenotype composition and metabolic properties of the stapedius and tensor tympani muscles in the human middle ear2023Inngår i: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 243, nr 1, s. 39-50Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The middle ear muscles have vital roles, yet their precise function in hearing and protection remains unclear. To better understand the function of these muscles in humans, the morphology, fiber composition, and metabolic properties of nine tensor tympani and eight stapedius muscles were analyzed with immunohistochemical, enzyme-histochemical, biochemical, and morphometric techniques. Human orofacial, jaw, extraocular, and limb muscles were used as references. The immunohistochemical analysis showed that the stapedius and tensor tympani muscles were markedly dominated by fibers expressing fast contracting myosin heavy chain MyHC-2A and MyHC-2X (79 ± 6% vs. 86 ± 9%, respectively, p = 0.04). In fact, the middle ear muscles had one of the highest proportions of MyHC-2 fibers ever reported for human muscles. Interestingly, the biochemical analysis revealed a MyHC isoform of unknown identity in both the stapedius and tensor tympani muscles. Muscle fibers containing two or more MyHC isoforms were relatively frequently observed in both muscles. A proportion of these hybrid fibers expressed a developmental MyHC isoform that is normally absent in adult human limb muscles. The middle ear muscles differed from orofacial, jaw, and limb muscles by having significantly smaller fibers (220 vs. 360 μm2, respectively) and significantly higher variability in fiber size, capillarization per fiber area, mitochondrial oxidative activity, and density of nerve fascicles. Muscle spindles were observed in the tensor tympani muscle but not in the stapedius muscle. We conclude that the middle ear muscles have a highly specialized muscle morphology, fiber composition, and metabolic properties that generally showed more similarities to orofacial than jaw and limb muscles. Although the muscle fiber characteristics in the tensor tympani and stapedius muscles suggest a capacity for fast, fine-tuned, and sustainable contractions, their difference in proprioceptive control reflects different functions in hearing and protection of the inner ear.

    Fulltekst (pdf)
    fulltext
  • 44.
    Skoglund, Elisabeth
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Department of Laboratory Medicine, Division of Clinical Physiology, Karolinska Institutet, and Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden; Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Sweden.
    Gronholdt-Klein, Max
    Rullman, Eric
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Strömberg, Anna
    Hedman, Anu
    Cederholm, Tommy
    Ulfhake, Brun
    Gustafsson, Thomas
    Longitudinal Muscle and Myocellular Changes in Community-Dwelling Men Over Two Decades of Successful Aging: The ULSAM Cohort Revisited2020Inngår i: The journals of gerontology. Series A, Biological sciences and medical sciences, ISSN 1079-5006, E-ISSN 1758-535X, Vol. 75, nr 4, s. 654-663Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Participants of the population-based Uppsala longitudinal study of adult men (ULSAM) cohort reaching more than 88 years of age (survivors, S) were investigated at age 70, 82, and 88-90 and compared at 70 years with non-survivors (NS) not reaching 82 years. Body composition, muscle mass and muscle histology were remarkably stable over 18 years of advanced aging in S. Analysis of genes involved in muscle remodeling showed that S had higher mRNA levels of myogenic differentiation factors (Myogenin, MyoD), embryonic myosin (eMyHC), enzymes involved in regulated breakdown of myofibrillar proteins (Smad2, Trim32, MuRF1,) and NCAM compared with healthy adult men (n = 8). S also had higher mRNA levels of eMyHC, Smad 2, MuRF1 compared with NS. At 88 years, S expressed decreased levels of Myogenin, MyoD, eMyHC, NCAM and Smad2 towards those seen in NS at 70 years. The gene expression pattern of S at 70 years was likely beneficial since they maintained muscle fiber histology and appendicular lean body mass until advanced age. The expression pattern at 88 years may indicate a diminished muscle remodeling coherent with a decline of reinnervation capacity and/or plasticity at advanced age.

    Fulltekst (pdf)
    fulltext
  • 45.
    Skoglund, Elisabeth
    et al.
    Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet and Unit of Clinical Physiology,Karolinska University Hospital, Stockholm, Sweden.
    Stål, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Lundberg, Tommy R.
    Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet and Unit of Clinical Physiology,Karolinska University Hospital, Stockholm, Sweden.
    Gustafsson, Thomas
    Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet and Unit of Clinical Physiology,Karolinska University Hospital, Stockholm, Sweden.
    Tesch, Per A.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Skeletal muscle morphology, satellite cells, and oxidative profile in relation to physical function and lifelong endurance training in very old men2023Inngår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 134, nr 2, s. 264-275Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the current study, we compared muscle morphology in three advanced aging cohorts that differed in physical function, includ-ing a unique cohort of lifelong endurance athletes. Biopsies from the vastus lateralis muscle of seven lifelong endurance athletes (EAs) aged 82-92 yr, and 19 subjects from the Uppsala Longitudinal Study of Adult Men (ULSAM) aged 87-91 yr were analyzed. ULSAM subjects were divided into high-(n = 9, HF) and low-(n = 10, LF) function groups based on strength and physical function tests. The analysis included general morphology, fiber type and cross-sectional area, capillarization, deficient cytochrome c oxi-dase (COX) activity, number of myonuclei and satellite cells, and markers of regeneration and denervation. Fibers with central nuclei and/or nuclear clumps were observed in all groups. EA differed from LF and HF by having a higher proportion of type I fibers, 52% more capillaries in relation to fiber area, fewer COX-negative fibers, and less variation in fiber sizes (all P < 0.05). There were no differences between the groups in the number of myonuclei and satellite cells per fiber, and no significant differ-ences between LF and HF (P > 0.05). In conclusion, signs of aging were evident in the muscle morphology of all groups, but neither endurance training status nor physical function influenced signs of regeneration and denervation processes. Lifelong en-durance training, but not higher physical function, was associated with higher muscle oxidative capacity, even beyond the age of 80.NEW & NOTEWORTHY Here we show that lifelong endurance training, but not physical function, is associated with higher mus-cle oxidative capacity, even beyond the age of 80 yr. Neither endurance training status nor physical function was significantly associated with satellite cells or markers of regeneration and denervation in muscle biopsies from these very old men.

  • 46.
    Soukup, T
    et al.
    Academy of Sciences of the Czech Republic, Prague.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Intrafusal fiber type composition of muscle spindles in the first human lumbrical muscle2003Inngår i: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 105, nr 1, s. 18-24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We studied muscle spindles in the first lumbrical muscle of adult humans using myofibrillar ATPase (mATPase) activity. We found that muscle spindles exhibited a marked variability with respect to the number, position, length and detailed histochemical features of nuclear bag1, nuclear bag2 and nuclear chain fibers. Regarding mATPase activity, the nuclear bag2 fibers displayed lower alkali-stable mATPase activity along their length and many nuclear bag1 fibers tended to have lower acid-stable activity in the outer B region, whereas nuclear chain fibers exhibited medium acid-stable mATPase activity at pH 4.6. Almost 10% of spindle fibers displayed atypical features, as they were either located only at one spindle pole or exhibited mixed characteristics at either pole. The number of intrafusal fibers per spindle varied between 8 and 24. Strikingly, only 2 pairs from 22 muscle spindles had identical allotments of their intrafusal fibers. Muscle spindles in the first human lumbrical muscle contained more intrafusal fibers (12.3 +/- 4 per spindle on average) and especially relatively more nuclear bag fibers compared to other human skeletal muscles. Since each spindle apparently represents a unique morphological and physiological entity, the observed variability in the number and characteristics of intrafusal fibers in the first human lumbrical muscle likely reflects a wide range of finely tuned muscle spindle responses.

  • 47.
    Stål, Per
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Marklund, Susanna
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Klinisk oral fysiologi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    De Paul, R
    Eriksson, Per-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Klinisk oral fysiologi.
    Fibre composition of human intrinsic tongue muscles.2003Inngår i: Cells Tissues Organs, ISSN 1422-6405, E-ISSN 1422-6421, Vol. 173, nr 3, s. 147-161Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The muscle fibre composition of three human intrinsic tongue muscles, the longitudinalis, verticalis and transversus, was investigated in four anterior to posterior regions of the tongue using morphological and enzyme- and immunohistochemical techniques. All three muscles typically contained type I, IIA and IM/IIC fibres. Type I fibres expressed slow myosin heavy chain (MyHC), type II fibres fast MyHC, mainly fast A MyHC, whereas type IM/IIC coexpressed slow and fast MyHCs. Type II fibres were in the majority (60%), but regional differences in proportion and diameter of fibre types were obvious. The anterior region of the tongue contained a predominance of relatively small type II fibres (71%), in contrast to the posterior region which instead showed a majority of larger type I and type IM/IIC fibres (66%). In general, the fibre diameter was larger in the posterior region. This muscle fibre composition of the tongue differs from those of limb, orofacial and masticatory muscles, probably reflecting genotypic as well as phenotypic functional specialization in oral function. The predominance of type II fibres and the regional differences in fibre composition, together with intricate muscle structure, suggest generally fast and flexible actions in positioning and shaping the tongue, during vital tasks such as mastication, swallowing, respiration and speech. Copyright 2003 S. Karger AG, Basel

  • 48. Tajsharghi, H
    et al.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Darin, N
    Martinsson, T
    Kyllerman, M
    Wahlström, J
    Oldfors, A
    Myosin heavy chain IIa gene mutation E706K is pathogenic and its expression increases with age2002Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 58, nr 5, s. 780-786Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The authors recently described a new autosomal dominant myopathy (OMIM 605637 inclusion body myopathy 3) associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene (MyHC IIa, Human Gene Map [HGM] locus MYH2). Young patients showed minor changes in their muscle biopsies, although dystrophic alterations and rimmed vacuoles with 15- to 20-nm tubulofilaments identical to those in sporadic inclusion body myositis (s-IBM) were observed in some of the adult (especially older) patients. The current study was undertaken to investigate the relation between expression of the mutant MyHC IIa and pathologic changes in muscle.

    METHODS: The expression of MyHC IIa in nine muscle specimens from six individuals carrying the mutation was analyzed by immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a new reverse transcriptase--PCR method to measure the relative abundance of the various MyHC transcripts.

    RESULTS: Young patients with muscle weakness and minor pathologic changes in muscle expressed MyHC IIa at undetectable levels. MyHC IIa was expressed at high levels in adults with a progressive clinical course and dystrophic muscle changes. In these cases, a large number of muscle fibers were hybrids with expression of more than one MyHC isoform. Both MyHC IIa alleles were equally expressed. The relative level of MyHC IIa transcripts exceeded that of the corresponding protein, indicating an increased turnover of mutated protein. MyHC IIa expression was a consistent finding in muscle fibers with rimmed vacuoles.

    CONCLUSIONS: The clear correlation between pathologic changes and expression of MyHC IIa indicates that defects in MyHC may lead not only to muscle weakness but also to muscle degeneration. The consistent expression of MyHC IIa in muscle fibers with rimmed vacuoles indicates that the breakdown of sarcomeric proteins is a key element in the pathogenesis of rimmed vacuoles of s-IBM type.

  • 49.
    Tajsharghi, Homa
    et al.
    Sahlgrenska University Hospital.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lindberg, Christopher
    Sahlgrenska University Hospital.
    Lindvall, Björn
    University Hospital, Linköping.
    Henriksson, Karl-Gösta
    University Hospital, Linköping.
    Oldfors, Anders
    Sahlgrenska University Hospital.
    Myosin storage myopathy associated with a heterozygous missense mutation in MYH72003Inngår i: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 54, nr 4, s. 494-500Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Myosin constitutes the major part of the thick filaments in the contractile apparatus of striated muscle. MYH7 encodes the slow/beta-cardiac myosin heavy chain (MyHC), which is the main MyHC isoform in slow, oxidative, type 1 muscle fibers of skeletal muscle. It is also the major MyHC isoform of cardiac ventricles. Numerous missense mutations in the globular head of slow/beta-cardiac MyHC are associated with familial hypertrophic cardiomyopathy. We identified a missense mutation, Arg1845Trp, in the rod region of slow/beta-cardiac MyHC in patients with a skeletal myopathy from two different families. The myopathy was characterized by muscle weakness and wasting with onset in childhood and slow progression, but no overt cardiomyopathy. Slow, oxidative, type 1 muscle fibers showed large inclusions consisting of slow/beta-cardiac MyHC. The features were similar to a previously described entity: hyaline body myopathy. Our findings indicate that the mutated residue of slow/beta-cardiac MyHC is essential for the assembly of thick filaments in skeletal muscle. We propose the term myosin storage myopathy for this disease.

  • 50.
    Thornell, Lars Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Ultrastructural and cytochemical studies on hearth purkinje fibres1974Doktoravhandling, med artikler (Annet vitenskapelig)
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