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  • 251.
    McLoon, Linda K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Department of Ophthalmology and Visual Neurosciences, University of Minnesota, 6 Minneapolis, MN 55455.
    Harandi, Vahid M
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Brännstrom, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wnt and Extraocular Muscle Sparing in Amyotrophic Lateral Sclerosis2014Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 55, nr 9, s. 5482-5496Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The extraocular muscles (EOM) and their motor neurons are spared in amyotrophic lateral sclerosis (ALS). In limb muscle axon retraction from the neuromuscular junctions occurs early in the disease. Wnts, a conserved family of secreted signaling molecules, play a critical role in neuromuscular junction formation. This is the first study to examine Wnt signaling for its potential involvement in maintenance of normal morphology in EOMs in ALS.

    METHODS: EOM and limb muscle axons, neuromuscular junctions, and myofibers from control, aging, and ALS patients and the SOD1G93A mouse model of ALS were quantified for their expression of Wnt1, Wnt3a, Wnt5a, Wnt7a, and beta-catenin.

    RESULTS: All four Wnt isoforms were expressed in most axon profiles in all human EOMs. Significantly fewer were positive for Wnt1, Wnt3a, and Wnt7a in the human limb muscles. Similar differential patterns in Wnt myofiber expression was also seen, except for Wnt7a, where expression was elevated. In the SOD1G93A mouse, all 4 Wnt isoforms were significantly decreased in the neuromuscular junctions at the terminal stage compared to age matched controls. Beta-catenin was activated in a subset of myofibers in EOM and limb muscle in all patients.

    CONCLUSIONS: The differences in Wnt expression in EOM and limb muscle, particularly at the neuromuscular junction level, suggest that they play a role in the pathophysiology of ALS. Collectively, the data support a role for Wnt signaling in the preservation of the EOM in ALS and their dysregulation and the subsequent development of pathology in the ALS limb muscles.

  • 252. McLoon, Linda K.
    et al.
    Vicente, André
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik.
    Fitzpatrick, Krysta R.
    Lindström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pedrosa Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles2018Inngår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, nr 1, s. 322-329Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally.

    Methods: Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment.

    Results: Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles.

    Conclusions: A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle.

  • 253.
    Mohanna, P N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. University of Manchester.
    Young, R C
    University of Manchester.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, G
    University of Manchester.
    A composite poly-hydroxybutyrate-glial growth factor conduit for long nerve gap repairs2003Inngår i: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 203, nr 6, s. 553-565Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is considerable evidence that peripheral nerves have the potential to regenerate in an appropriate microenvironment. We have developed a novel artificial nerve guide composed of poly 3-hydroxybutyrate (PHB) filled with glial growth factor (GGF) suspended in alginate hydrogel. Gaps of 2-4 cm in rabbit common peroneal nerve were bridged using a PHB conduit containing either GGF in alginate hydrogel (GGF) or alginate alone (Alginate), or with an empty PHB conduit (Empty). Tissues were harvested 21, 42 and 63 days post-operatively. Schwann cell and axonal regeneration were assessed using quantitative immunohistochemistry. At 21 days, addition of GGF increased significantly the distance of axonal and Schwann cells regeneration in comparison with that observed in Alginate and Empty conduits for both gap lengths. The axons bridged the 2-cm GGF conduits gap by 63 days, with a comparable rate of regeneration seen in 4-cm conduits. Schwann cells and axonal regeneration quantity was similar for both gap lengths in each group. However, at all time points the quantity of axonal and Schwann cells regeneration in GGF grafts was significantly greater than in both Alginate and Empty conduits, the latter showing better regeneration than Alginate conduits. The results indicate an inhibitory effect of alginate on regeneration, which is partially reversed by the addition of GGF to the conduits. In conclusion, GGF stimulates a progressive and sustainable regeneration increase in long nerve gap conduits.

  • 254. Mohanna, Pari-Naz
    et al.
    Terenghi, Giorgio
    Wiberg, Mikael
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi. Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Handkirurgi.
    Composite PHB-GGF conduit for long nerve gap repair: a long-term evaluation2005Inngår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 39, nr 3, s. 129-137Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two to four cm nerve gaps in the rabbit common peroneal nerve were bridged with poly-3-hydroxybutyrate (PHB) conduits containing either glial growth factor (GGF) (PHB-GGF) or alginate matrix (PHB-ALG), and with empty PHB conduit (E-PHB). PHB-GGF significantly increased nerve regeneration up to 63 days following repair of long nerve gaps and the regeneration was sustained long term leading to motor organ reinnervation. At 120 days postoperatively, GGF addition significantly increased the quantity of Schwann cell and axonal regeneration compared to those in control conduits. In PHB-GGF conduits there were more minifascicles of myelinated fibres compared to the controls. The distal nerve of PHB-GGF and E-PHB conduits showed greater regeneration than that of PHB-ALG grafts, although all distal nerves contained fewer myelinated fibres than grafted conduits. Consistently, PHB-GGF conduits significantly reduced the muscle mass percentage loss compared to controls. In conclusion, GGF-containing conduits promoted sustained axonal regeneration and improved target muscle reinnervation.

  • 255. Monemi, M
    et al.
    Kadi, F
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, L E
    Eriksson, P O
    Adverse changes in fibre type and myosin heavy chain compositions of human jaw muscle vs. limb muscle during ageing.1999Inngår i: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 167, nr 4, s. 339-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This review shows that human jaw muscles not only have unique fibre type and myosin heavy chain (MyHC) compositions but also undergo muscle and region-specific changes in fibre composition during ageing. Alterations in the masseter and the lateral pterygoid muscles in the elderly are opposite to those reported for limb and trunk muscles, whereas changes in the anterior and posterior bellies of the digastric muscle resemble those of limb and trunk muscles. We conclude that age-related alterations in fibre type composition and MyHC expression are muscle and region specific, probably reflecting muscular differences in genetic programs and epigenetic influences.

  • 256.
    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.

  • 257.
    Mousavizadeh, Rouhollah
    et al.
    Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
    Backman, Ludvig
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    McCormack, Robert G
    Department of Orthopedic Surgery, University of British Columbia, Vancouver, BC, Canada.
    Scott, Alex
    Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
    Dexamethasone decreases substance P expression in human tendon cells: an in vitro study2015Inngår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 54, nr 2, s. 318-323Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Glucocorticoid injections are used by rheumatologists to treat chronic tendinopathy. Surprisingly, the mechanisms by which corticosteroids induce pain relief in this condition have not been investigated. Previous studies have shown local substance P (SP) levels to be correlated with tendon pain and tissue pathology. The objective of this study was to determine whether SP production in human tenocytes is modulated by exposure to dexamethasone.

    METHODS: Human tendon fibroblasts were cultured in the presence or absence of dexamethasone (1-400 nM), an inhibitor of the glucocorticoid receptor, RU486, recombinant TGF-β (2.5 or 5.0 ng/ml) or an inhibitor of the TGF-β receptor (A83.01), recombinant human IL-1β and IL-6. Expression levels of the genes encoding for SP (TAC1) and its preferred receptor (NK1R), IL-1α, IL-1β and IL-6 were determined with quantitative PCR and protein levels of SP were examined by EIA and western blot.

    RESULTS: Exposure of human tendon cells to dexamethasone resulted in a time-dependent reduction of mRNA for SP in both hamstrings and Achilles tenocytes, whereas NK1R was unaffected. The reduction of SP mRNA was dependent on signalling through the glucocorticoid receptor. SP protein was substantially decreased by dexamethasone. Dexamethasone also prevented induction of SP by IL-1β and by cyclic mechanical loading.

    CONCLUSION: This study demonstrates that dexamethasone treatment of human tendon fibroblasts reduces the expression of SP through a glucocorticoid receptor-dependent pathway. Drugs interfering with SP signalling could be a future target in the treatment of tendinopathy.

  • 258. 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.

  • 259.
    Nilsson, Emma C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Storm, Rickard J
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Bauer, Johannes
    University of Tübingen.
    Johansson, Susanne M C
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Lookene, Aivar
    Tallinn University of Technology, Tallinn, Estonia..
    Ångström, Jonas
    University of Göteborg.
    Hedenström, Mattias
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Eriksson, Therese L
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Frängsmyr, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Rinaldi, Simon
    University of Glasgow.
    Willison, Hugh J
    University of Glasgow.
    Domellöf, Fatima Pedrosa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Stehle, Thilo
    University of Tübingen, Vanderbilt University School of Medicine.
    Arnberg, Niklas
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis (Letter)2011Inngår i: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 17, nr 1, s. 105-109Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC.

  • 260.
    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.

  • 261.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Labeling of central projections of primary afferents in adult rats: a comparison between biotinylated dextran amine, neurobiotin and Phaseolus vulgaris-leucoagglutinin.2001Inngår i: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 112, nr 2, s. 145-154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The efficacy of anterograde labeling of the central projections of primary afferent fibers were compared between biotinylated dextran amine (BDA), neurobiotin (NB) and Phaseolus vulgaris-leucoagglutinin (PHA-L) after injections into the L5 or T13 dorsal root ganglia (DRGs) of adult rats. Excellent labeling was obtained with BDA, which visualized fibers with fine terminal boutons in the L5 and T13 spinal cord segments, Clarke's nucleus and the gracile nucleus. Rarely observed crossed projections to the gracile nucleus and L5 ventral horn of the contralateral side could also be distinguished. Even in the most successful experiments, however, BDA labeled only about one-third of the axons originating from the injected dorsal root ganglion. BDA was also efficient as transganglionic tracer after application to the transected sciatic nerve. NB produced no significant labeling of the L5 primary afferents, and was only moderately effective on the T13 level. PHA injections resulted in sparse terminal labeling of the T13 and L5 afferents. Thus, BDA is an effective tracer for long-range labeling of primary afferent projections in the spinal cord and brain stem. Since not all stem fibers become labeled, however, the method does not allow quantification of all axon branches and terminals arising from the injected DRGs.

  • 262.
    Novikov, Lev N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikova, Liudmila N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Holmberg, P
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kellerth, J
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Exogenous brain-derived neurotrophic factor regulates the synaptic composition of axonally lesioned and normal adult rat motoneurons2000Inngår i: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 100, nr 1, s. 171-181Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Brain-derived neurotrophic factor has previously been shown to promote survival and axonal regeneration in injured spinal motoneurons and, also, to modulate synaptic transmission and regulate the density of synaptic innervation in a variety of neurons. The present light and electron microscopic study demonstrates synaptotrophic effects of exogenously applied brain-derived neurotrophic factor on the synaptic composition of both normal and axonally lesioned adult rat spinal motoneurons. After L5-L6 ventral root avulsion, a massive loss of all types of boutons occurred on the somata of the lesioned motoneurons which persisted for at least 12 weeks postoperatively. We found that (i) intrathecal infusion of brain-derived neurotrophic factor during the first postoperative week did not prevent the synaptic detachment and activation of glial cells; (ii) prolonged treatment for four weeks restored synaptic covering and significantly reduced microglial reaction; (iii) the synaptotrophic effect remained significant for at least eight weeks after cessation of the treatment; (iv) brain-derived neurotrophic factor mainly supported F-type boutons with presumably inhibitory function, while it had little effect on S-type boutons associated with excitatory action; and (v) in normal unlesioned motoneurons, four weeks of treatment with brain-derived neurotrophic factor induced sprouting of F-type boutons, a loss of S-type boutons and motoneuron atrophy. The present data show that exogenous neurotrophins not only help to restore synaptic circuitry in axonally injured motoneurons, but also strongly influence the synaptic composition in normal motoneurons.

  • 263.
    Novikov, Lev N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikova, Liudmila N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Mosahebi, Afshin
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Kellerth, Jan-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    A novel biodegradable implant for neuronal rescue and regeneration after spinal cord injury.2002Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 23, nr 16, s. 3369-76Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    After spinal cord injury, the severed neuronal pathways fail to regenerate spontaneously. This study describes a biodegradable implant using poly-beta-hydroxybutyrate (PHB) fibers as carrier scaffold for matrix components and cell lines supporting neuronal survival and regeneration after spinal cord injury. After cervical spinal cord injury in adult rats, a graft consisting of PHB fibers coated with alginate hydrogel + fibronectin was implanted in the lesion cavity. In control groups, PHB was omitted and only alginate hydrogel or fibronectin, or their combination, were used for grafting. In addition, comparisons were made with animals treated intrathecally after spinal cord injury with the neurotrophic factors BDNF or NT-3. The neurons of the rubrospinal tract served as experimental model. In untreated animals, 45% of the injured rubrospinal neurons were lost at 8 weeks postoperatively. Implantation of the PHB graft reduced this cell loss by 50%, a rescuing effect similar to that obtained after treatment with BDNF or NT-3. In the absence of PHB support, implants of only alginate hydrogel or fibronectin, or their combination, had no effect on neuronal survival. After addition of neonatal Schwann cells to the PHB graft, regenerating axons were seen to enter the graft from both ends and to extend along its entire length. These results show that implants using PHB as carrier scaffold and containing alginate hydrogel, fibronectin and Schwann cells can support neuronal survival and regeneration after spinal cord injury

  • 264.
    Novikova, Liudmila
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Effects of nerve graft implantation technique on axonal regeneration after spinal cord injury2008Inngår i: Journal of Neurodegeneration and Regeneration, Vol. 1, nr 1, s. 43-49Artikkel i tidsskrift (Fagfellevurdert)
  • 265.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Brohlin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kingham, Paul J
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Neuroprotective and growth-promoting effects of bone marrow stromal cells after cervical spinal cord injury in adult rats2011Inngår i: Cytotherapy, ISSN 1465-3249, E-ISSN 1477-2566, Vol. 13, nr 7, s. 873-887Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background aims. Bone marrow stromal cells (BMSC) have been shown to provide neuroprotection after transplantation into the injured central nervous system. The present study investigated whether adult rat BMSC differentiated along a Schwann cell lineage could increase production of trophic factors and support neuronal survival and axonal regeneration after transplantation into the injured spinal cord.

    Methods. After cervical C4 hemi-section, 5-bromo-2-deoxyuridine (BrdU)/green fluorescent protein (GFP)-labeled BMSC were injected into the lateral funiculus at 1 mm rostral and caudal to the lesion site. Spinal cords were analyzed 2-13 weeks after transplantation.

    Results and Conclusions. Treatment of native BMSC with Schwann cell-differentiating factors significantly increased production of brain-derived neurotrophic factor in vitro. Transplanted undifferentiated and differentiated BMSC remained at the injection sites, and in the trauma zone were often associated with neurofilament-positive fibers and increased levels of vascular endothelial growth factor. BMSC promoted extensive in-growth of serotonin-positive raphaespinal axons and calcitonin gene-related peptide (CGRP)-positive dorsal root sensory axons into the trauma zone, and significantly attenuated astroglial and microglial cell reactions, but induced aberrant sprouting of CGRP-immunoreactive axons in Rexed's lamina III. Differentiated BMSC provided neuroprotection for axotomized rubrospinal neurons and increased the density of rubrospinal axons in the dorsolateral funiculus rostral to the injury site. The present results suggest that BMSC induced along the Schwann cell lineage increase expression of trophic factors and have neuroprotective and growth-promoting effects after spinal cord injury.

  • 266.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lobov, Sergei
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Efficacy of olfactory ensheathing cells to support regeneration after spinal cord injury is influenced by method of culture preparation2011Inngår i: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 229, nr 1, s. 132-142Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Olfactory ensheathing cells (OEC) have been shown to stimulate regeneration, myelination and functional recovery in different spinal cord injury models. However, recent reports from several laboratories have challenged this treatment strategy. The discrepancy in results could be attributed to many factors including variations in culture protocols. The present study investigates whether the differences in culture preparation could influence neuroprotective and growth-promoting effects of OEC after transplantation into the injured spinal cord. Primary OEC cultures were purified using method of differential cell adhesion (a-OEC) or separated with immunomagnetic beads (b-OEC). After cervical C4 hemisection in adult rats, short-term (3weeks) or long-term (7weeks) cultured OEC were transplanted into the lateral funiculus at 1mm rostral and caudal to the transection site. At 3-8weeks after transplantation, labeled OEC were mainly found in the injection sites and in the trauma zone. Short-term cultured a-OEC supported regrowth of rubrospinal, raphaespinal and CGRP-positive fibers, and attenuated retrograde degeneration in the red nucleus. Short-term cultured b-OEC failed to promote axonal regrowth but increased the density of rubrospinal axons within the dorsolateral funiculus and provided significant neuroprotection for axotomized rubrospinal neurons. In addition, short-term cultured OEC attenuated sprouting of rubrospinal terminals. In contrast, long-term cultured OEC neither enhanced axonal growth nor prevented retrograde cell death. The results suggest that the age of OEC in culture and the method of cell purification could affect the efficacy of OEC to support neuronal survival and regeneration after spinal cord injury.

  • 267.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Mosahebi, Afshin
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Kellerth, Jan-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation.2006Inngår i: Journal of Biomedical Materials Research part A, ISSN 1549-3296, Vol. 77, nr 2, s. 242-252Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were compared between olfactory ensheathing cells (OECs), Schwann cells (SCs), and bone marrow stromal cells (BMSCs). Neurite outgrowth from embryonic dorsal root ganglia (DRG) neurons was used to assess the efficacy of the hydrogels alone or in combination with cultured cells to promote axonal regeneration. The result showed that alginate hydrogel transformed OECs, SCs, and BMSCs into atypical cells with spherical shape and inhibited their metabolic activity. Combination of alginate hydrogel with fibronectin promoted only OECs proliferation. Alginate hydrogel also inhibited outgrowth of DRG neurites, although this effect was attenuated by addition of fibronectin, SCs, or BMSCs. In contrast, matrigel stimulated cell proliferation, preserved the typical morphological features of the cultured cells and induced massive sprouting of DRG neurites. Addition of cultured cells to matrigel did not further improve DRG neurite outgrowth. The present findings suggest that addition of extracellular matrix should be considered when engineering biosynthetic scaffolds on the basis of alginate hydrogels.

  • 268.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kellerth, J O
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    BDNF abolishes the survival effect of NT-3 in axotomized Clarke neurons of adult rats2000Inngår i: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 428, nr 4, s. 671-680Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) have previously been shown to support survival and axonal regeneration in various types of neurons. Also, synergistic neuroprotective effects of these neurotrophins have been reported in descending rubrospinal neurons after cervical spinal cord injury (Novikova et al., [2000] Eur. J. Neurosci. 12:776-780). The present study investigates the effects of intrathecally delivered NT-3 and BDNF on the survival and atrophy of ascending spinocerebellar neurons of Clarke nucleus (CN) after cervical spinal cord injury in adult rats. At 8 weeks after cervical spinal cord hemisection, 40% of the axotomized CN neurons had been lost, and the remaining cells exhibited marked atrophy. Microglial activity was significantly increased in CN of the operated side. Intrathecal infusion of NT-3 for 8 weeks postoperatively resulted in 91% cell survival and a reduction in cell atrophy, but did not reduce microglial activity. In spite of the fact that the CN neurons expressed both TrkC and TrkB receptors, only NT-3 had a neuroprotective effect, whereas BDNF was ineffective. Furthermore, when a combination of BDNF and NT-3 was administered, the neuroprotective effect of NT-3 was lost. The present results indicate a therapeutic potential for NT-3 in the treatment of spinal cord injury, but also demonstrate that in certain neuronal populations the neuroprotection obtained by a combination of neurotrophic factors may be less than that of a single neurotrophin.

  • 269.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kellerth, J O
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Survival effects of BDNF and NT-3 on axotomized rubrospinal neurons depend on the temporal pattern of neurotrophin administration2000Inngår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 12, nr 2, s. 776-780Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study shows that both BDNF and NT-3 can prevent cell death in axotomized adult rat rubrospinal neurons (RSNs), but that the efficacy of neuroprotection depends on the temporal pattern of treatment. At 8 weeks after cervical spinal cord injury, 51% of the RSNs had died. Subarachnoidal BDNF infusion into the cisterna magna for 4 weeks resulted in neuronal hypertrophy and 71% survival. Continuous infusion for 8 weeks into the lumbar subarachnoidal space with either BDNF or NT-3 gave similar survival rates, while a combination of BDNF and NT-3 resulted in 96% survival, although the cells were atrophic. When administration of either BDNF or NT-3 was delayed and performed during postoperative weeks 5-8, the number of surviving neurons was increased compared to early treatment. Delayed treatment with a combination of BDNF and NT-3 resulted in complete survival and a reduction in neuronal atrophy. A decreased expression of TrkB receptors and microtubule-associated protein-2 in the RSNs after axotomy was counteracted by BDNF and NT-3. Microglial activity remained increased even when complete cell survival was achieved. Thus, the combination of neurotrophins as well as the temporal pattern of treatment need to be adequately defined to optimize survival of injured spinal tract neurons.

  • 270.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kellerth, Jan-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Biopolymers and biodegradable smart implants for tissue regeneration after spinal cord injury.2003Inngår i: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 16, nr 6, s. 711-5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE OF REVIEW: This article reviews recent experimental advances in the development of biosynthetic implants for repair of spinal cord injury.

    RECENT FINDINGS: Various important advances in the development of biosynthetic conduits for spinal cord repair have recently been reported. It was found that implantation of freeze dried alginate sponge into completely transected spinal cord supports axonal regeneration across the lesion site. A poly(lactic-co-glycolic acid) scaffold seeded with neural stem cells has been developed that promotes axonal regeneration across the gap. It was found that polyethylene glycol can reseal damaged spinal cord axons and restore impulse conduction. Findings have been reported that poly-beta-hydroxybutyrate conduits in combination with alginate and fibronectin provide neuroprotection for axotomized descending neurones. It has been reported that conduits made of fibronectin mats or fibrin in combination with neurotrophic growth factors promote axonal growth into the grafts. Finally, magnetic resonance imaging after experimental spinal cord injury has been used to monitor regeneration in biosynthetic conduits in vivo over time.

    SUMMARY: Biosynthetic conduits carrying extracellular matrix molecules and different cell lines, and supplemented with neurotrophic growth factors have yielded encouraging results in the treatment of experimental spinal cord injury. These findings provide a basis for further development of techniques aimed at spinal cord repair in humans.

  • 271.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kellerth, Jan-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Differential effects of neurotrophins on neuronal survival and axonal regeneration after spinal cord injury in adult rats.2002Inngår i: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 452, nr 3, s. 255-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Spinal cord injury (SCI) induces retrograde cell death in descending pathways, which can be prevented by long-term intrathecal infusion of neurotrophins (Novikova et al. [2000] Eur J Neurosci 12:776-780). The present study investigates whether the same treatment also leads to improved regeneration of the injured tracts. After cervical SCI in adult rats, a peripheral nerve graft was attached to the rostral wall of the lesion cavity. The animals were treated by local application into the cavity of Gelfoam soaked in (1) phosphate buffered saline (untreated controls) or (2) a mixture of the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) (local treatment), or by intrathecal infusion of BDNF + NT-3 for (3) 2 weeks (short-term treatment) or (4) 5-8 weeks (long-term treatment). Despite a very strong survival effect, long-term treatment failed to stimulate ingrowth of descending tracts into the nerve graft. In comparison with untreated controls, the latter treatment also caused 35% reduction in axonal sprouting of descending pathways rostral to the lesion site and 72% reduction in the number of spinal cord neurons extending axons into the nerve graft. Local and short-term treatments neither prevented retrograde cell death nor enhanced regeneration of descending tracts, but induced robust regeneration of spinal cord neurons into the nerve graft. These results indicate that the signal pathways promoting neuronal survival and axonal regeneration, respectively, in descending tracts after SCI respond differently to neurotrophic stimuli and that efficient rescue of axotomized tract neurons is not a sufficient prerequisite for regeneration.

  • 272.
    Novikova, Liudmila N
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pettersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Brohlin, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Biodegradable poly-beta-hydroxybutyrate scaffold seeded with Schwann cells to promote spinal cord repair2008Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 29, nr 9, s. 1198-1206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cavity formation is an important obstacle impeding regeneration after spinal cord injury and bridging strategies are essential to provide physical substrate allowing axons to grow across the lesion site. In this study we evaluated effects of biodegradable tubular conduit made from poly-beta-hydroxybutyrate (PHB) scaffold with predominantly unidirectional fiber orientation and supplemented with cultured adult Schwann cells on axonal regeneration after cervical spinal cord injury in adult rats. After transplantation into the injured spinal cord, plain PHB conduit was well-integrated into posttraumatic cavity and induced modest astroglial reaction. Regenerating axons were found mainly outside the PHB with only single fibers crossing the host-graft interface. No host Schwann cells migrated into the graft. In contrast, when suspension of adult Schwann cells was added to the PHB during transplantation, neurofilament-positive axons filled the conduit and became associated with the implanted cells. Although rubrospinal fibers did not enter the PHB, numerous raphaespinal and CGRP-positive axons were found within the conduit. Modification of PHB surface with fibronectin, laminin or collagen significantly increased Schwann cell attachment and proliferation in vitro. However, transplantation of PHB conduit pre-coated with fibronectin and seeded with Schwann cells did not alter axonal growth response. The results demonstrate that a PHB scaffold promotes attachment, proliferation and survival of adult Schwann cells and supports marked axonal regeneration within the graft.

  • 273.
    Nyström, Alexander
    et al.
    Department of Experimental Medical Science, Division for Cell and Matrix Biology, Lund University.
    Holmblad, Johanna
    Department of Experimental Medical Science, Division for Cell and Matrix Biology, Lund University.
    Pedrosa-Domellöf, Fatima
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Sasaki, Takako
    Max-Planck-Institut für Biochemie, Martinsried, Germany.
    Durbeej, Madeleine
    Department of Experimental Medical Science, Division for Cell and Matrix Biology, Lund University.
    Extraocular muscle is spared upon complete laminin alpha2 chain deficiency: comparative expression of laminin and integrin isoforms.2006Inngår i: Matrix Biology, ISSN 0945-053X, E-ISSN 1569-1802, Vol. 25, nr 6, s. 382-385Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutations in the gene encoding laminin (LM) alpha2 chain cause congenital muscular dystrophy. Here, we show that extraocular muscle (EOM) is spared upon complete LMalpha2 chain absence. The major LM chains in limb muscle basement membranes are alpha2, beta1, beta2 and gamma1 whereas alpha2, alpha4, beta1, beta2 and gamma1 chains are expressed in EOM. Expression of LMalpha4 chain mRNA is further increased in LMalpha2 chain deficient EOM. Mainly integrin alpha7X1 subunit, which binds to laminin-411, is expressed in EOM and in contrast to dystrophic limb muscle, sustained integrin alpha7B expression is seen in LMalpha2 chain deficient EOM. We propose that LMalpha4 chain, possibly by binding to integrin alpha7BX1beta1D, protects EOM in LMalpha2 chain deficient muscular dystrophy.

  • 274. 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)
  • 275.
    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.

  • 276. 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.

  • 277.
    Ouasti, Sihem
    et al.
    University of Manchester.
    Kingham, Paul J
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. University of Manchester.
    Terenghi, Giorgio
    University of Manchester.
    Tirelli, Nicola
    University of Manchester.
    The CD44/integrins interplay and the significance of receptor binding and re-presentation in the uptake of RGD-functionalized hyaluronic acid2012Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, nr 4, s. 1120-1134Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have studied the interplay between two endocytic receptors for a carrier structure bearing two complementary ligands. Hyaluronic acid (HA; three different molecular weights) was functionalized with an RGD-containing peptide; this ancillary ligand allows the macromolecule to bind to alpha(v) integrins in addition to the classical HA internalization receptor (CD44). The uptake of HA-RGD and of native HA was assessed in a phagocytic cell model (J774.2 murine macrophages), studying the kinetics of internalization and its mechanistic details. Indications of a synergic binding to integrins and CD44 emerged for HA-RGD; possibly, a first binding to integrins allows for a pre-concentration of the macromolecule on the cell surface, which is then followed by its binding to CD44. The endocytic mechanism and kinetics appeared then dominated by CD44, which has a much slower turnover than integrins. In this study we have demonstrated that the knowledge of the rate-determining steps of the internalization of a carrier is necessary for assessing its performance. In this case, the presence of multiple ligands on a carrier was beneficial in some respect (e.g. in improved binding/targeting), but may not be sufficient to overcome penetration barriers that arise from slow receptor re-presentation. (C) 2011 Elsevier Ltd. All rights reserved.

  • 278.
    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.

  • 279.
    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.

  • 280.
    Persson-Sjögren, S
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Forsgren, S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Shi, C L
    Täljedal, I B
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Mouse islets cultured with vasoactive intestinal polypeptide: effects on insulin release and immunoreactivity for tyrosine hydroxylase.2001Inngår i: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 22, nr 1, s. 84-90Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mouse islets cultured for 1 or 4 days with or without 10 nM vasoactive intestinal polypeptide (VIP) were stained for tyrosine hydroxylase (TH) and examined for insulin secretion during culture and in a postculture perifusion system. Exposure to exogenous VIP for 4 days increased the frequency of islet cells expressing TH-like immunoreactivity. Regardless of the culturing conditions, the islets exhibited significant insulin secretory responses to 16.7 mM glucose, the effect being potentiated by 10 nM VIP in the perifusion medium. The insulin-releasing action of glucose and the potentiating effect of VIP were less pronounced in islets cultured for 1 day with VIP than in islets cultured without this neuropeptide. The following conclusions are suggested: (a) VIP stimulates the expression of TH in mouse islet cells; (b) the latency of the VIP-induced TH is a postreceptor phenomenon; (c) islet cultures exposed to VIP represent a new instance of the association between increased functional demands on beta cells and enhanced expression of TH and a new instance of VIP having trophic effects.

  • 281.
    Persson-Sjögren, S
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Forsgren, S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Täljedal, I B
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Tyrosine hydroxylase in mouse pancreatic islet cells, in situ and after syngeneic transplantation to kidney.2002Inngår i: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 17, nr 1, s. 113-21Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tyrosine hydroxylase (TH) is co-expressed with islet hormones in the fetal mouse pancreas. In the adult animal, the enzyme has been considered as a marker of ageing beta-cells. By immunohistochemical staining, we analyzed the expression of TH-like immunoreactivity (TH-LI), insulin-LI (INS-LI) and somatostatin-LI (SOM-LI) in adult mouse islets, in situ and after isolation and transplantation to kidney. In pancreas in situ, most TH-LI cells expressed INS-LI while less than 5% expressed SOM-LI. The total number of TH-LI cells/mm2 was significantly increased directly after isolation and in 0-day, 12-week and 52-week old grafts, but not in 3-day grafts. The proportion of TH-LI cells expressing SOM-LI increased after transplantation, amounting to about one-third by 52 weeks. As expressed per unit islet area, the frequencies of both TH/INS and TH/SOM cells increased significantly in the transplants. The results demonstrate that TH occurs in both beta-cells and D-cells of adult islets. In both cell types the enzyme appears to be responsive to the microenvironmental changes inherent in transplantation. This cellular phenotype plasticity might contribute to the altered insulin secretory dynamics in islet grafts.

  • 282.
    Persson-Sjögren, S
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Zashihin, A
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Forsgren, S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Nerve cells associated with the endocrine pancreas in young mice: an ultrastructural analysis of the neuroinsular complex type I.2001Inngår i: The Histochemical Journal, ISSN 0018-2214, E-ISSN 1573-6865, Vol. 33, nr 6, s. 373-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The neuroinsular complex type 1 is composed of pancreatic endocrine islet cells and nerve cell bodies intrinsic to the islet. The details of the relation between nerve cells and between endocrine cells and nerve cells in the complex are unknown. Pancreata from newborn and 18-day-old mice were analysed by electron microscopy to establish the ultrastructural morphology of the neuroinsular complex. Immunohistochemical staining for protein gene-product 9.5 was also performed. The study showed that nerve cell bodies were closely associated to each other in the periphery of the islets with no connective tissue separating the cells. The nerve cells were closely associated to both beta-cells and alpha-cells. Direct intercellular contacts were observed between nerve cells and endocrine cells and between Schwann cells and endocrine cells. Varicose nerve endings were frequently observed in the neuroinsular complex. In the peripheral parts the varicosities were mostly being associated to the nerve cell bodies. The varicosities contained small clear or small clear and larger dense cored vesicles, suggesting cholinergic and peptidergic contents. The varicosities made specialized synaptic connections with adjacently located nerve cells. The study shows that the neuronal part of the neuroinsular complex is closely associated to the endocrine islet cells and that it is richly innervated, indicating an important regulatory function of the nerve cell component in the neuroinsular complex.

  • 283.
    Persson-Sjögren, Solveig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi. Histologi med cellbiologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Anatomi.
    Lindström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi. Histologi med cellbiologi.
    Vasoactive intestinal polypeptide and pituitary adenylate cyclase activating polypeptide: effects on insulin release in isolated mouse islets in relation to metabolic status and age.2006Inngår i: Neuropeptides, ISSN 0143-4179, Vol. 40, nr 4, s. 283-90Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Obesity and development of the metabolic syndrome is related to an increased parasympathetic tone and hyperinsulinemia. We have now studied the effects of age and metabolic status on glucose-induced insulin release stimulated by the neuropeptides vasoactive intestinal polypeptide (VIP; 10 nM) and pituitary adenylate cyclase activating polypeptide (PACAP; 10 nM), that are constituents of the parasympathetic nerves in the islets, and the cholinergic agonists acetylcholine (ACh; 10 microM) and carbachol (10 microM), in isolated islets from female obese ob/ob mice and lean mice. Both VIP and PACAP enhanced insulin secretion in islets from 4-week-old hyperglycemic ob/ob mice. VIP did not increase 11.1 mM glucose-induced insulin release in islets from 4-week-old lean normoglycemic mice and neither did PACAP in the absence of bicarbonate. The neuropeptides increased insulin release in islets from 9 to 10-month-old mice but VIP and PACAP had no effect in islets from very old mice. ACh had no effect in islets from 9 to 10-months and older ob/ob mice in the absence of bicarbonate. The combination of VIP and cholinergic agonists had an additive effect in islets from ob/ob mice, and PACAP combined with carbachol potentiated insulin release in islets from 4-week-old lean mice. VIP increased early phase insulin release in perifused islets from young mice. A higher concentration of theophylline was needed to potentiate glucose-induced insulin release in islets from young lean mice than in islets from old lean mice and ob/ob mice. The present results demonstrate age-related dynamics in the effects of neuropeptides affecting cAMP in pancreatic islets. We suggest that VIP and PACAP contribute to the developing metabolic syndrome in ob/ob mice by aggravating hyperinsulinemia.

  • 284.
    Persson-Sjögren, Solveig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Holmberg, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Remodeling of the innervation of pancreatic islets accompanies insulitis preceding onset of diabetes in the NOD mouse.2005Inngår i: Journal of Neuroimmunology, ISSN 0165-5728, Vol. 158, nr 1-2, s. 128-37Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The innervation of the islets of Langerhans may constitute a first target for the autoimmunity that develops in type 1 diabetes. Here, we report the occurrence of a decrease in general innervation within the islets in the nonobese diabetic (NOD) mouse, and the establishment of strands of Schwann cells, as detected via p75 and S-100 immunoreactivity (IR), and varicose nerve fibers expressing tyrosine kinase A (TrkA) in association with the immune cells. The findings suggest that there are marked attempts for neurotrophins to promote nerve ingrowth and survival for islet tissue and that remodeling of innervation occurs in the continuation of the insulitis process preceding the onset of type 1 diabetes.

  • 285.
    Persson-Sjögren, Solveig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Holmberg, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Forsgren, Sture
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Expression of the NK-1 receptor on islet cells and invading immune cells in the non-obese diabetic mouse2005Inngår i: Journal of Autoimmunity, ISSN 0896-8411, Vol. 24, nr 4, s. 269-279Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The underlying mechanistic causes of immune cell infiltration in the islets of Langerhans and beta cell failure in the non-obese diabetic (NOD) mouse is still to be completely revealed. Substance P (SP) is a substance known to have pro-inflammatory, endocrine, neuromodulatory and trophic effects, and its preferred receptor, the neurokinin receptor 1 (NK-1 R), is reported to be involved in extravasation of granulocytes and in inflammation and tissue derangement. Therefore, we have investigated the expression of NK-1 R during development of insulitis in the NOD mouse. We show that the magnitude of immunoreactivity scoring NK-1 R expression in the islets was increased in the 12-week-old NOD mouse. Expression of NK-1 R co-localized with expression of glucagon. In line with this expression pattern, we did not detect any effect of SP on glucose-induced insulin release. NK-1 R expression was particularly observed in islet cells in association with the clusters of immune cells. Expression of NK-1 R was also demonstrated in a fraction of the infiltrating B and T lymphocytes, as well as on infiltrating macrophages and dendritic cells. The observations show that the level of NK-1 R expression is increased in 12-week-old NOD mice, being correlated with the occurrence of islet mononuclear infiltration. Our data suggest that SP may act as a chemoattractant, contributing to the pathogenic mononuclear infiltration process in the NOD mouse. On the whole, the observations suggest that SP and the NK-1 R to certain extents are involved in the changes that occur during the development of insulitis in the NOD mouse.

  • 286.
    Pettersson, Jonas
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Holmström, Anna
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Hill, Jim
    Biomedical Sciences Department, Defence Evaluation and Research Agency, Porton Down, Salisbury, Wiltshire SP4 OJQ, UK.
    Leary, Sophie
    Biomedical Sciences Department, Defence Evaluation and Research Agency, Porton Down, Salisbury, Wiltshire SP4 OJQ, UK.
    Frithz-Lindsten, Elisabet
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    von Euler-Matell, Anne
    Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
    Carlsson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Titball, Richard
    Biomedical Sciences Department, Defence Evaluation and Research Agency, Porton Down, Salisbury, Wiltshire SP4 OJQ, UK.
    Forsberg, Åke
    Swedish Defence Research Agency, Division of CBRN Defence and Security, SE-901 82 Umeå, Sweden.
    Wolf-Watz, Hans
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    The V-antigen of Yersinia is surface exposed before target cell contact and involved in virulence protein translocation:  1999Inngår i: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 32, nr 5, s. 961-976Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Type III-mediated translocation of Yop effectors is an essential virulence mechanism of pathogenic Yersinia. LcrV is the only protein secreted by the type III secretion system that induces protective immunity. LcrV also plays a significant role in the regulation of Yop expression and secretion. The role of LcrV in the virulence process has, however, remained elusive on account of its pleiotropic effects. Here, we show that anti-LcrV antibodies can block the delivery of Yop effectors into the target cell cytosol. This argues strongly for a critical role of LcrV in the Yop translocation process. Additional evidence supporting this role was obtained by genetic analysis. LcrV was found to be present on the bacterial surface before the establishment of bacteria target cell contact. These findings suggest that LcrV serves an important role in the initiation of the translocation process and provides one possible explanation for the mechanism of LcrV-induced protective immunity.

  • 287.
    Pettersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kalbermatten, Daniel
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    McGrath, Aleksandra
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Novikova, Liudmila N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Biodegradable fibrin conduit promotes long-term regeneration after peripheral nerve injury in adult rats2010Inngår i: Journal of Plastic, Reconstructive & Aesthetic Surgery, ISSN 1748-6815, E-ISSN 1532-1959, Vol. 63, nr 11, s. 1893-1899Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peripheral nerve injuries are often associated with loss of nerve tissue and require autologous nerve grafts to provide a physical substrate for axonal growth. Biosynthetic neural conduits could be an alternative treatment strategy in such injuries. The present study investigates the long-term effects of a tubular fibrin conduit on neuronal regeneration, axonal sprouting and recovery of muscle weight following peripheral nerve injury and repair in adult rats. Sciatic axotomy was performed proximally in the thigh to create a 10-mm gap between the nerve stumps. The injury gap was bridged by using a 14-mm-long fibrin glue conduit, entubulating 2mm of the nerve stump at each end. A reversed autologous nerve graft was used as a control. The regenerative response from sensory and motor neurones was evaluated following retrograde labelling with Fast Blue fluorescent tracer. In control experiments, at 16 weeks following peripheral nerve grafting, 5184 (+/-574 standard error of mean (SEM)) sensory dorsal root ganglion neurones and 1001 (+/-37 SEM) spinal motor neurones regenerated across the distal nerve-graft interface. The fibrin conduit promoted regeneration of 60% of sensory neurones and 52% of motor neurones when compared to the control group. The total number of myelinated axons in the distal nerve stump in the fibrin-conduit group reached 86% of the control and the weight of gastrocnemius and soleus muscles recovered to 82% and 89% of the controls, respectively. The present results suggest that a tubular fibrin conduit can be used to promote neuronal regeneration following peripheral nerve injury.

  • 288.
    Pettersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lobov, Sergei
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikova, Liudmila N
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Labeling of olfactory ensheathing glial cells with fluorescent tracers for neurotransplantation2010Inngår i: Brain Research Bulletin, ISSN 0361-9230, E-ISSN 1873-2747, Vol. 81, nr 1, s. 125-132Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Development of cell-based treatment strategies for repair of the injured nervous system requires cell tracing techniques to follow the fate of transplanted cells and their interaction with the host tissue. The present study investigates the efficacy of fluorescent cell tracers Fast Blue, PKH26, DiO and CMFDA for long-term labeling of olfactory ensheathing glial cells (OEC) in culture and following transplantation into the rat spinal cord. All tested dyes produced very efficient initial labeling of p75-positive OEC in culture. The number of Fast Blue-positive cells remained largely unchanged during the first 4 weeks but only about 21% of the cells retained tracer 6 weeks after labeling. In contrast, the number of cells labeled with PKH26 and DiO was reduced to 51-55% after 2 weeks in culture and reached 8-12% after 4-6 weeks. CMFDA had completely disappeared from the cells 2 weeks after labeling. AlamarBlue assay showed that among four tested tracers only CMFDA reduced proliferation rate of the OEC. After transplantation into spinal cord, Fast Blue-labeled OEC survived for at least 8 weeks but demonstrated very limited migration from the injection sites. Additional immunostaining with glial and neuronal markers revealed signs of dye leakage from the transplanted cells resulted in weak labeling of microglia and spinal neurons. The results show that Fast Blue is an efficient cell marker for cultured OEC. However, transfer of the dye from the transplanted cells to the host tissue should be considered and correctly interpreted.

  • 289.
    Pettersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    McGrath, Aleksandra
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Kalbermatten, Daniel
    University Hospital of Basel.
    Novikova, Liudmila
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Kingham, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Muscle recovery after repair of short and long peripheral nerve gaps using fibrin conduits2011Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 500, nr 1, s. 41-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peripheral nerve injuries with loss of nervous tissue are a significant clinical problem and are currently treated using autologous nerve transplants. To avoid the need for donor nerve, which results in additional morbidity such as loss of sensation and scarring, alternative bridging methods have been sought. Recently we showed that an artificial nerve conduit moulded from fibrin glue is biocompatible to nerve regeneration. In this present study, we have used the fibrin conduit or a nerve graft to bridge either a 10 mm or 20 mm sciatic nerve gap and analyzed the muscle recovery in adult rats after 16 weeks. The gastrocnemius muscle weights of the operated side were similar for both gap sizes when treated with nerve graft. In contrast, muscle weight was 48.32 ± 4.96% of the contra-lateral side for the 10 mm gap repaired with fibrin conduit but only 25.20 ± 2.50% for the 20 mm gap repaired with fibrin conduit. The morphology of the muscles in the nerve graft groups showed an intact, ordered structure, with the muscle fibers grouped in fascicles whereas the 20 mm nerve gap fibrin group had a more chaotic appearance. The mean area and diameter of fast type fibers in the 20 mm gap repaired with fibrin conduits were significantly (P < 0.01) worse than those of the corresponding 10 mm gap group. In contrast, both gap sizes treated with nervegraft showed similar fiber size. Furthermore, the 10 mm gaps repaired with either nerve graft or fibrin conduit showed similar muscle fiber size. These results indicate that the fibrin conduit can effectively treat short nerve gaps but further modification such as the inclusion of regenerative cells may be required to attain the outcomes of nerve graft for long gaps.

  • 290.
    Pettersson, Linda F.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kingham, Paul J.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Kelk, Peyman
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    In Vitro Osteogenic Differentiation of Human Mesenchymal Stem Cells from Jawbone Compared with Dental Tissue2017Inngår i: Tissue Engineering and Regenerative Medicine, ISSN 1738-2696, Vol. 14, nr 6, s. 763-774Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Autologous bone transplantation is the current gold standard for reconstruction of jawbone defects. Bone regeneration using mesenchymal stem cells (MSC) is an interesting alternative to improve the current techniques, which necessitate a second site of surgery resulting in donor site morbidity. In this study, we compared the osteogenic ability of jawbone MSC (JB-MSC) with MSC from tissues with neural crest origin, namely, the dental pulp, apical papilla and periodontal ligament. All four types of MSC were isolated from the same patient (n = 3 donors) to exclude inter-individual variations. The MSC growth and differentiation properties were characterized. The osteogenic differentiation potential in each group of cells was assessed quantitatively to determine if there were any differences between the cell types. All cells expressed the MSC-associated surface markers CD73, CD90, CD105, and CD146 and were negative for CD11b, CD19, CD34, CD45 and HLA-DR. All cell types proliferated at similar rates, exhibited similar clonogenic activity and could differentiate into adipocytes and osteoblasts. An alkaline phosphatase assay, OsteoImageTM assay for mineralization and qRT-PCR measuring the genes runx2, ALP and OCN, indicated that there were no significant differences in the osteogenic differentiation ability between the various MSCs. In conclusion, we show that from a small segment of jawbone it is possible to isolate sufficient quantities of MSC and that these cells can easily be expanded and differentiated into osteoblasts. JB-MSC appear to be good candidates for future bone regeneration applications in the craniofacial region.

  • 291.
    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.

  • 292. Piedrahita, Hugo
    et al.
    Oksa, Juha
    Malm, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Rintamäki, Hannu
    Health problems related to working in extreme cold conditions indoors.2008Inngår i: International Journal of Circumpolar Health, ISSN 1239-9736, E-ISSN 2242-3982, Vol. 67, nr 2-3, s. 279-87Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To identify health problems among workers performing cleaning, maintenance and machine operation tasks inside cold storage rooms with temperatures between -43 degrees C and -62 degrees C in a freeze drying coffee company. STUDY DESIGN: Descriptive study. METHODS: All 24 workers working inside the cold stores participated in the study. A questionnaire about cold-related health problems and the standardized Nordic questionnaire assessing muscle complaints were completed by all exposed workers. A physical examination was performed on each worker. RESULTS: The most relevant cold-related health problem was episodic finger symptoms (50%), followed by respiratory symptoms (21%), peripheral circulation symptoms (20%), and repeated pain in the musculoskeletal system (12%). Two subjects had a previous diagnosis of Raynaud's phenomenon (RP). The prevalence of musculoskeletal complains in the neck and low back was 21% in each. CONCLUSIONS: The prevalence found for various complaints among the freeze drying coffee workers implies that the cold conditions inside cold stores may present a real risk of cold-related health problems and, due to lowered concentration level, for injuries, too. Greater efforts should be made to minimize the cold exposure by designing automation processes to prevent continuous exposure to cold during freeze drying process. In addition, improving the cold-protective clothing and guaranteeing its appropriate use will reduce health risks.

  • 293. Piedrahita, Hugo
    et al.
    Oksa, Juha
    Malm, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Sormunen, Erja
    Rintamäki, Hannu
    Effects of cooling and clothing on vertical trajectories of the upper arm and muscle functions during repetitive light work.2008Inngår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 104, nr 2, s. 183-91Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The present study was designed to find out if cooling and/or clothing affect the vertical trajectories and muscle function of the upper arm during repetitive light work. Twelve female subjects performed a one-handed lifting task for 60 min while standing in front of a table with six target angles (30 degrees to 220 degrees ). The experiment was carried out in a climatic chamber in three different conditions: at 10 degrees C (C), at 25 degrees C (TN), and at 10 degrees C dressed in cold-protective clothing (C(p)). Skin and rectal temperatures were measured continuously. The vertical trajectories of the head, shoulder, elbow, and wrist on the right side of the body were recorded. Muscular strain (averaged EMG, a-EMG) and EMG gaps in eight muscles on the right upper arm were measured. The variation of the vertical trajectory amplitude of the upper arm measured from the elbow was significantly higher (at 200 degrees ) both at C and C(p) (50 and 25% respectively) and in shoulder (at 220 degrees angle) at C (33%) compared with TN (P < 0.05). Both C and C(p) increased a-EMG and reduced the number and duration of EMG gaps significantly in all muscles studied. In conclusion, in repetitive tasks the high mean vertical trajectory and changes in the amplitude of the trajectory of the upper arm at C and C(p) compared with TN were associated with increased muscular strain and reduced number of EMG gaps (more continuous activation of given muscle fibers). The changes in trajectories may serve as indicator of a risk for local muscle fatigue.

  • 294.
    Piedrahita, Hugo
    et al.
    Luleå University of Technology Human Work Sciences Department 97187 Luleå Sweden.
    Oksa, Juha
    Finnish Institute of Occupational Health Physical Work Capacity Team 90220 Oulu Finland.
    Rintamäki, Hannu
    Finnish Institute of Occupational Health Physical Work Capacity Team 90220 Oulu Finland.
    Malm, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Effect of local leg cooling on upper limb trajectories and muscle function and whole body dynamic balance2009Inngår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 105, nr 3, s. 429-438Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study was designed to find out if local leg cooling affects muscle function and trajectories of the upper limb during repetitive light work as well as capability to maintain dynamic balance. Nine healthy female subjects performed repetitive lifting task with right hand for 60 min while standing in front of a table with six target angles (30 degrees -220 degrees ) and with the legs inside a container with 15 degrees C cold water (Cold condition, C) or without water (Normal condition, N). Muscle temperature of the medial aspect of the gastrocnemius, rectal, and skin temperatures were measured continuously. The trajectories of the right upper limb were recorded with a 3D motion analysis system. Muscular strain (averaged EMG, a-EMG) and EMG gaps in eight muscles of the right upper limb were measured. End point excursion depicting the ability to maintain dynamic balance was measured before and after each experiment. Leg cooling decreased significantly (P < 0.05) the muscle and the mean skin temperature in C compared with N (6.7 and 2.2 degrees C, respectively). No marked changes in the trajectories or EMG activity were observed between the different environmental conditions. The end point excursion was significantly (P < 0.05) reduced in C compared with N and a positive correlation between excursion and muscle temperature was found at the end of the working period in C. In conclusion, local leg cooling did not affect upper limb muscle function or trajectories, but ability to maintain dynamic balance was reduced.

  • 295. Plantman, Stefan
    et al.
    Novikova, Liudmila
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Novikov, Lev
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Hammarberg, Henrik
    Wallquist, Wilhelm
    Kellerth, Jan-Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Cullheim, Staffan
    Integrin messenger RNAs in the red nucleus after axotomy and neurotrophic administration.2005Inngår i: Neuroreport, ISSN 0959-4965, Vol. 16, nr 7, s. 709-13Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Integrins are cell surface receptors known to be important for regeneration in the peripheral nervous system. We have investigated the expression of integrin messenger RNAs in red nucleus neurons of adult rats after axotomy and administration of neurotrophic factors. Using radioactive in situ hybridization, messenger RNA for integrin subunits beta1, alpha3, alpha7 and alphaV could be detected. No change of any alpha subunit could be detected after axotomy. In contrast, a small upregulation of beta1 was detected after lesion. Administration of neurotrophin-3 induced a robust further increase in beta1 messenger RNA levels, whereas brain-derived neurotrophic factor did not. By analogy to the peripheral nervous system, we propose that integrins may be important for a regenerative response in central nervous system neurons.

  • 296.
    Pontén, Eva
    et al.
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Fridén, Jan
    Immobilization of the rabbit tibialis anterior muscle in a lengthened position causes addition of sarcomeres in series and extra-cellular matrix proliferation.2008Inngår i: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 41, nr 8, s. 1801-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rabbits were immobilized for 3 weeks with the ankle in plantar flexion, midrange position or dorsal extension (n=15). The left leg was used as control. Sarcomere lengths were measured by laser diffraction in vivo in the tibialis anterior (TA) muscle. Legs immobilized in the midrange position showed coherent diffraction patterns through the range of motion, but in those immobilized with TA in the stretched position no diffraction patterns in vivo could be obtained. Morphological analyses revealed increased fibrosis and occurrence of whorled fibers in these muscles. On 15 more likewise immobilized rabbits, a technique of measuring sarcomere lengths in vitro by first digesting the collagen in nitric acid was developed. These in vitro measurements showed shorter sarcomeres in the muscles immobilized in a lengthened position compared to the control, indicating an addition of sarcomeres in series.

  • 297. Pontén, Eva
    et al.
    Fridén, Jan
    Thornell, Lars-Eric
    Umeå universitet, Medicinsk fakultet, Integrativ medicinsk biologi, Anatomi.
    Lieber, Richard L
    Spastic wrist flexors are more severely affected than wrist extensors in children with cerebral palsy.2005Inngår i: Developmental Medicine and Child Neurology, ISSN 0012-1622, Vol. 47, nr 6, s. 384-9Artikkel 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.

  • 298.
    Pontén, Eva
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Lindström, Mona
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Kadi, Fawzi
    Higher amount of MyHC IIX in a wrist flexor in tetraplegic compared to hemiplegic cerebral palsy.2007Inngår i: J Neurol Sci, ISSN 0022-510XArtikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Spastic cerebral palsy can be divided into diagnostic groups by the relative severity of the arm impairment. This study investigates if hemiplegic, tetraplegic or diplegic cerebral palsy (CP) results in different patterns of myosin heavy chain (MyHC) expression in the flexor carpi ulnaris muscle from 17 young patients with CP. Using enzyme-immunohistochemistry and gel electrophoresis techniques we found a higher percentage of fibers expressing fast MyHC IIx (52%) in tetraplegic CP compared to hemiplegic patients (32%), (p&lt;0.05). Tetraplegic CP also resulted in a lower amount of fibers expressing slow MyHC I (18%) compared to hemiplegic CP (40%), (p&lt;0.005). The proportion of muscle fibers containing fetal MyHC was higher in tetraplegic CP compared to other groups, (p&lt;0.005). Taken together theses results indicate that tetraplegic CP is associated with a shift from slow to fast myosins and that regenerative events are more prominent in tetraplegic CP compared with milder brain damage.

  • 299.
    Pontén, Eva M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Stål, Per S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Decreased capillarization and a shift to fast myosin heavy chain IIx in the biceps brachii muscle from young adults with spastic paresis.2007Inngår i: J Neurol Sci, ISSN 0022-510X, Vol. 253, nr 1-2, s. 25-33Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Muscle spasticity and paresis are conditions that occur secondary to upper motor neuron lesions. The co-existence of decreased motor unit recruitment and intermittent over-activity generates confusion concerning the effect on muscle fiber characteristics. In order to increase the knowledge about the effect of upper motor lesion on capillarization and muscle fiber composition, the biceps brachii muscle from seven young adults with long duration of spastic paresis and seven age-matched controls were analyzed using morphological and enzyme- and immuno-histochemical techniques. The spastic muscles had a 38% lower capillary density (p=0.002), 30% fewer capillaries around each muscle fiber (p=0.02), and 16% fewer capillaries when related to the fiber size (p=0.04). The frequency of fibers expressing myosin heavy chain (MyHC) IIx increased (30% vs. 4%, p=0.006), while the percentage of fibers expressing MyHC I and MyHC IIa, respectively, decreased (22% vs. 46% and 7% vs. 29%, p&lt;0.01). The high proportion of muscle fibers with low oxidative capacity and low capillary supply indicates that biceps brachii muscle from patients with upper motor lesions fatigue more easily than normal controls. We also observed a significantly higher variability in fiber size for fibers expressing MyHC I (p&lt;0.04), and, in three of the subjects, a small amount of small fibers expressing developmental MyHCs was found. These results suggest that, although intermittent stretch reflex contractions might have an impact on the muscle characteristics in spastic paresis, the muscle phenotypic properties are more adapted to decreased voluntary motor unit recruitment.

  • 300.
    Preet, Raman
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Khan, Nausheen
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Blomstedt, Yulia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Nilsson, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Stewart Williams, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Priority Research Centre for Generational Health and Ageing, Faculty of Health and Medicine, University of Newcastle, Newcastle, NSW, Australia.
    Assessing dental professionals' understanding of tobacco prevention and control: a qualitative study in Västerbotten County, Sweden2016Inngår i: BDJ Open, ISSN 2056-807X, nr 2, s. 1-6, artikkel-id 16009Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To assess dental professionals’ understanding of tobacco prevention and control.

    Materials and methods: In Sweden dental hygienists receive training in tobacco prevention and control. The study setting is Västerbotton County in the north of Sweden where a number of successful tobacco control initiatives have been established. A purposeful sample comprising five male and four female dental professionals and trainees was selected. Data were collected through in-depth semi-structured individual interviews and analysed using content analysis.

    Results: Informants acknowledged limited adherence to tobacco prevention. They were not confident of their knowledge of tobacco and non-communicable disease prevention and had limited awareness of global oral health policies. Reasons for poor adherence included professional fragmentation, lack of training, and the absence of reimbursement for time spent on prevention activities.

    Discussion: The success of efforts to reduce smoking in Västerbotton County is attributed to the network of local public health initiatives with very limited involvement by local dental professionals.

    Conclusions: The findings highlight the need to more actively engage the dental workforce in tobacco control and prevention. Moreover, it is important to recognise that dental professionals can be public health advocates for tobacco control and prevention at global, national and local levels.

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