| 1. |
- Casar-Borota, Olivera, et al.
(författare)
-
A novel dynamin-2 gene mutation associated with a late-onset centronuclear myopathy with necklace fibres
- 2015
-
Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 25:4, s. 345-348
-
Tidskriftsartikel (refereegranskat)abstract
- Nuclear centralisation and internalisation, sarcoplasmic radiating strands and type 1 muscle fibre predominance and hypotrophy characterise dynamin-2 (DNM2) associated centronuclear myopathy, whereas necklace fibres are typically seen in late onset myotubularin-1 (MTM1)-related myopathy. We report a woman with unilateral symptoms probably related to brachial plexus neuritis. Electromyography revealed localised neuropathic and generalised myopathic abnormalities. The typical features of DNM2 centronuclear myopathy with additional necklace fibres were found in the muscle biopsy. Sequencing of the DNM2 and MTM1 genes revealed a novel heterozygous missense mutation in exon 18 of the DNM2, leading to replacement of highly conserved proline at position 647 by arginine. The muscle symptoms have not progressed during the 3-year follow-up. However, the patient has developed bilateral subtle lens opacities. Our findings support the concept that necklace fibres may occasionally be found in DNM2-related myopathy, possibly indicating a common pathogenic mechanism in DNM2 and MTM1 associated centronuclear myopathy. (C) 2015 Elsevier B.V. All rights reserved.
|
|
| 2. |
- Casar-Borota, Olivera, et al.
(författare)
-
A novel dynamin-2 gene mutation associated with a late-onset centronuclear myopathy with unusual clinical presentation and necklace fibres
- 2012
-
Ingår i: Neuromuscular Disorders. - Oxford : Elsevier BV. - 0960-8966 .- 1873-2364. ; 22:9-10, s. 843-843
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Nuclear centralisation and internalisation, sarcoplasmic radiating strands and type 1 muscle fibre predominance and hypotrophy are morphologic features of centronuclear myopathy (CNM) related to dynamin-2 (DNM2) gene defects, whereas necklace fibres characterise late-onset myopathy associated with myotubularin-1 (MTM1) gene defects. We report a 40-year-old woman with 1-year history of pain and paresthesia in the left shoulder and arm that was clinically interpreted as brachial plexus neuritis. Electromyography revealed both myopathic and neuropathic abnormalities, and because of the myopathic changes a muscle biopsy was performed. The typical morphologic features of dynamin-2 CNM with additional numerous necklace fibres were found in the muscle biopsy. Sequencing of the DNM2 and MTM1 genes revealed a not previously described heterozygous missense mutation in exon 18 of DNM2 leading to replacement of highly conserved Proline in position 647 by Arginine. The muscle symptoms have not progressed during the two-year follow-up, but the patient has developed bilateral subtle lens opacities. Necklace fibres were originally described as fibres that had usually a small diameter and internalized nuclei aligned in a basophilic ring at a few micrometers beneath the sarcolemma. They were described in association with myopathies caused by MTM1 mutations, and similar but not identical fibres have also been reported in a case of DNM2 associated CNM. Our findings support the concept that necklace fibres are not specific but indicate common pathogenic mechanisms in DNM2 and MTM1 associated CNM. This case report expands the clinical, morphological and molecular genetic variability of DNM2 associated CNM.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Libelius, Rolf, et al.
(författare)
-
Uptake of horseradish peroxidase in denervated skeletal muscle occurs primarily at the endplate region
- 1984
-
Ingår i: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 66, s. 273-281
-
Tidskriftsartikel (refereegranskat)abstract
- The spatial distribution of horseradish peroxidase (HRP) uptake has been studied by light- and electron microscopy in the denervated hemidiaphragm of the mouse. Segments with high HRP uptake were observed in a band centrally located in the denervated muscle. This distribution is similar to the well-known innervation pattern of the diaphragm. Ultrastructural studies demonstrated a high incidence of postsynaptic folds in close proximity of fibre areas with high intracellular content of HRP. 8–12 days after denervation a large number of fibres showed segments of high HRP uptake. 2–4 days after denervation very few such segments were observed. Biochemical studies also demonstrated an increase in HRP uptake after denervation occurring primarily in the endplate region. The activities of the lysosomal enzymes N-acetyl-β-d-glucosaminidase, acid phosphatase and cathepsin D all increased after denervation, most prominently in the endplate region.It is suggested that the observed segmental uptake of HRP and lysosomal activation reflects a process for rapid membrane turnover in denervated muscle.
|
|
| 7. |
- Linder, Jan, 1957-, et al.
(författare)
-
Anal sphincter electromyography in patients with newly diagnosed idiopathic parkinsonism
- 2012
-
Ingår i: Acta Neurologica Scandinavica. - Hoboken, NJ : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 126:4, s. 248-255
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives The differential diagnosis of patients with idiopathic parkinsonism is difficult, especially early in the course of the disease. External anal sphincter electromyography (EAS-EMG) has been reported to be of value in the differential diagnosis between Parkinson's disease (PD) and multiple system atrophy (MSA). Patients with MSA are reported to have pathological EAS-EMG and patients with PD are reported to have significantly less pathological EAS-EMG results. Comparisons between patients with parkinsonian disorders have usually been made many years into the disease, and thus it is largely unknown if the results of EAS-EMG can be used to distinguish the different diagnoses in the early phase of the disease. Materials and Methods We investigated 148 newly diagnosed patients with idiopathic parkinsonism from a population-based incidence cohort (100 definite PD, 21 probable PD, 16 MSA, 11 progressive supranuclear palsy, and 40 controls) with EAS-EMG within 3 months of their first visit and, in the majority of patients, before start of treatment with dopaminergic drugs. The clinical diagnoses were made using established clinical diagnostic criteria after a median follow-up of 3 years. Results All patient groups had more pathological EAS-EMG results than controls. No EAS-EMG differences were found between the patient groups, especially not between PD and MSA. Conclusions External anal sphincter electromyography examination cannot separate the different parkinsonian subgroups from each other in early course of the diseases.
|
|
| 8. |
|
|
| 9. |
- Norman, Holly, et al.
(författare)
-
Myofibrillar protein and gene expression in acute quadriplegic myopathy
- 2009
-
Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 285:1-2, s. 28-38
-
Tidskriftsartikel (refereegranskat)abstract
- The dramatic muscle wasting, preferential loss of myosin and impaired muscle function in intensive care unit (ICU) patients with acute quadriplegic myopathy (AQM) have traditionally been suggested to be the result of proteolysis via specific proteolytic pathways. In this study we aim to investigate the mechanisms underlying the preferential loss of thick vs. thin filament proteins and the reassembly of the sarcomere during the recovery process in muscle samples from ICU patients with AQM. Quantitative and qualitative analyses of myofibrillar protein and mRNA expression were analyzed using SDS-PAGE, confocal microscopy, histochemistry and real-time PCR. The present results demonstrate that the transcriptional regulation of myofibrillar protein synthesis plays an important role in the loss of contractile proteins, as well as the recovery of protein levels during clinical improvement, myosin in particular, presumably in concert with proteolytic pathways, but the mechanisms are specific to the different thick and thin filament proteins studied.
|
|
| 10. |
|
|
| 11. |
- Sellin, L C, et al.
(författare)
-
Membrane and biochemical alterations after denervation and during reinnervation of mouse skeletal muscle
- 1980
-
Ingår i: Acta Physiologica Scandinavica. ; 110:2, s. 181-186
-
Tidskriftsartikel (refereegranskat)abstract
- Denervation of the extensor digitorum longus (EDL) muscle of the mouse by either nerve crush or nerve section produced: a reduction of the resting membrane potential (Em), alterations in the properties of muscle fibre action potentials and the development of tetrodotoxin (TTX)-resistant action potentials. These changes in membrane electrical properties were accompanied by an increase in the endocytic activity of the muscle and an increase in the activities of the lysosomal enzymes cathepsin D and N-acetylglucosaminidase (NAGA). Reinnervation of muscle was indicated at 9 days after nerve crush by the presence of miniature end-plate potentials. The recovery of membrane electrical properties, beginning with the onset of reinnervation, were not temporally related. The Em increased in two stages: an early rapid repolarization and a later slower repolarization. The muscle fibers were sensitive to the blocking action of TTX by 12 days after nerve crush, whereas the rate of rise (dV/dt) of the action potential did not approach values of innervated muscles until 21 days. Reinnervation resulted in a decrease in endocytosis and a decrease in the activities of cathepsin D and NAGA toward innervated values by 21 days after nerve crush. The results suggest that membrane alterations after denervation and during reinnervation may occur by endo- and exocytosis of membrane constituents and that the lysosomal system may play a role in the breakdown and/or recycling of these structures.
|
|
| 12. |
- Svensson, Anna, et al.
(författare)
-
Secreted frizzled related protein 1 (Sfrp1) and Wnt signaling in innervated and denervated skeletal muscle.
- 2008
-
Ingår i: Journal of Molecular Histology. - : Springer Science and Business Media LLC. - 1567-2379 .- 1567-2387. ; 39:3, s. 329-337
-
Tidskriftsartikel (refereegranskat)abstract
- Wnts are secreted proteins with functions in differentiation, development and cell proliferation. Wnt signaling has also been implicated in neuromuscular junction formation and may function in synaptic plasticity in the adult as well. Secreted frizzled-related proteins (Sfrps) such as Sfrp1 can function as inhibitors of Wnt signaling. In the present study a potential role of Wnt signaling in denervation was examined by comparing the expression levels of Sfrp1 and key proteins in the canonical Wnt pathway, Dishevelled, glycogen synthase kinase 3 beta and beta-catenin, in innervated and denervated rodent skeletal muscle. Sfrp1 mRNA and immunoreactivity were found to be up-regulated in mouse hemidiaphragm muscle following denervation. Immunoreactivity, detected by Western blots, and mRNA, detected by Northern blots, were both expressed in extrasynaptic as well as perisynaptic parts of the denervated muscle. Immunoreactivity on tissue sections was, however, found to be concentrated postsynaptically at neuromuscular junctions. Using beta-catenin levels as a readout for canonical Wnt signaling no evidence for decreased canonical Wnt signaling was obtained in denervated muscle. A role for Sfrp1 in denervated muscle, other than interfering with canonical Wnt signaling, is discussed.
|
|
| 13. |
|
|
| 14. |
- Svensson, Anna, et al.
(författare)
-
Semaphorin 6C expression in innervated and denervated skeletal muscle.
- 2008
-
Ingår i: Journal of molecular histology. - : Springer Science and Business Media LLC. - 1567-2379 .- 1567-2387. ; 39:1, s. 5-13
-
Tidskriftsartikel (refereegranskat)abstract
- Semaphorins are secreted or transmembrane proteins important for axonal guidance and for the structuring of neuronal systems. Semaphorin 6C, a transmembrane Semaphorin, has growth cone collapsing activity and is expressed in adult skeletal muscle. In the present study the expression of Semaphorin 6C mRNA and immunoreactivity has been compared in innervated and denervated mouse hind-limb and hemidiaphragm muscles. Microscopic localization of immunoreactivity was studied in innervated and denervated rat skeletal muscle. The results show that Semaphorin 6C mRNA expression and immunoreactivity on Western blots are down-regulated following denervation. The mRNA of Semaphorin 6C as well as immunoreactivity determined by Western blots are expressed in extrasynaptic as well as perisynaptic regions of muscle. Immunohistochemical studies, however, show Semaphorin 6C-like immunoreactivity to be concentrated at neuromuscular junctions. The results suggest a role for Semaphorin 6C in neuromuscular communication.
|
|
| 15. |
- Tågerud, Sven, et al.
(författare)
-
An ultrastructural study of the segmental uptake of horseradish peroxidase in the endplate region of denervated skeletal muscle fibres
- 1986
-
Ingår i: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 75:2, s. 141-157
-
Tidskriftsartikel (refereegranskat)abstract
- The segmental uptake of horseradish peroxidase (HRP) in the endplate region of denervated skeletal muscle fibres has been studied ultrastructurally using a method for selecting single muscle fibres with high segmental peroxidase staining from denervated mouse tibialis anterior muscle.Segments containing large peroxidase positive phagosomes could already be seen 10–15 min after i.v. injection of HRP. Such segments were still present 24 h after HRP injection. The localization of phagosomes, deep in the fibres rather than immediately under the sarcolemma, suggests that the uptake occurs from t-tubuli. Vivid proliferation of t-tubuli, consisting of vesiculation, enlargement and encircling of cytoplasmic components, was also observed. The HRP accumulates in phagosomes of varying size and shape. Similar membrane-limited bodies without or with very weak peroxidase staining were also observed. The peroxidase-positive phagosomes participate in autophagic processes as suggested by their content of undegraded cellular material. Golgi profiles, which occurred deep in the muscle fibres, and enlarged components of the sarcoplasmic reticulum were frequently encountered in the segments. Myofibrillar degeneration occurs in the segments and progresses with time after denervation.The described segments may be related to the increased membrane turnover in denervated muscle fibres and/or they may be related to processes aimed at establishing new synaptic contacts.
|
|
| 16. |
- Tågerud, Sven, et al.
(författare)
-
Biochemical and ultrastructural effects of chloroquine on horseradish peroxidase uptake and lysosomal enzyme activities in innervated and denervated mouse skeletal muscle
- 1986
-
Ingår i: Journal of the Neurological Sciences. - 0022-510X .- 1878-5883. ; 75:2, s. 159-171
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of chloroquine treatment on horseradish peroxidase (HRP) uptake and lysosomal enzyme activities in innervated and denervated mouse skeletal muscle have been studied using biochemical, histochemical and ultrastructural techniques.Chloroquine treatment caused a large (59–101%) increase in the activity of cathepsin D in both innervated and denervated muscle. The activity of N-acetyl-β-d-glucosaminidase also increased slightly in denervated muscle. No effect was observed on acid phosphatase activity. The in vivo uptake of HRP in innervated and denervated muscle was unaffected by chloroquine treatment. The results show that the activities of certain lysosomal enzymes may increase in skeletal muscle without an increase in endocytic activity. This is discussed in comparison to what is seen in denervated and dystrophic muscle.Histochemical and ultrastructural studies showed the HRP uptake to occur segmentally in denervated muscle fibres from untreated as well as chloroquine-treated animals. Ultrastructurally the peroxidase-positive phagosomes occurring in these segments were found to contain increased levels of undegraded material after chloroquine treatment suggesting that these phagosomes are of a lysosomal nature and also participate in autophagic processes.
|
|
| 17. |
- Tågerud, Sven, et al.
(författare)
-
Effects of botulinum toxin induced muscle paralysis on endocytosis and lysosomal enzyme activities in mouse skeletal muscle
- 1986
-
Ingår i: Pflügers Archive European Journal of Physiology. - 0031-6768. ; 407:3, s. 275-278
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of botulinum toxin (type A) induced muscle paralysis on endocytosis and lysosomal enzyme activities in skeletal muscle were compared with the effects of surgical denervation. Muscle atrophy, measured as decrease in total muscle protein content, was as large or larger after botulinum toxin treatment as after denervation. Endocytic activity, measured as the in vitro uptake of horseradish peroxidase, and the specific activities of the lysosomal enzymes N-acetyl--d-glucosaminidase and cathepsin D were all increased six days after denervation. Only the specific activity of cathepsin D was increased six days after botulinum toxin poisoning. The uptake of horseradish peroxidase and the specific activity of N-acetyl--d-glucosamidase were also increased eleven days after poisoning. Transverse sections of eleven days botulinum poisoned muscles from animals injected with horseradish peroxidase showed fibres with dense peroxidase staining similar to those seen in denervated muscle although they seemed to occur less frequently.The results show that increases in endocytic activity and lysosomal enzyme activities may occur in skeletal muscle without the presence of degenerating axons. The differences in effects of surgical denervation and botulinum toxin induced paralysis are discussed in terms of what is known about the mechanism of action of botulinum toxin and the possible functional roles of the two lysosomal enzymes studied.
|
|
| 18. |
- Tågerud, Sven, et al.
(författare)
-
High endocytotic and lysosomal activities in segments of rat myotubes differentiated in vitro
- 1990
-
Ingår i: Cell and Tissue Research. - 0302-766X .- 1432-0878. ; 259, s. 225-232
-
Tidskriftsartikel (refereegranskat)abstract
- Endocytosis and the lysosome system have beenstudied in rat myotubes differentiated in vitro. Horseradishperoxidase was used as marker for endocytosis and wasfound to accumulate unevenly in the myotubes. Small segmentsof myotubes display very high endocytotic activity.Similar segments contained numerous lysosomes, as seenby the accumulation of neutral red or histochemical stainingfor acid phosphatase. The segments also contained accumulationsof acetylcholine receptors as determined by bindingof tetramethyl rhodamine-labelled c~-bungarotoxin. Unstainedsegments in living cultures could be recognized byphase-contrast microscopy since they often appeared somewhatdilated and were not as well spread on the culturesurface as the main parts of the myotubes. Ultrastructurally,the segments contained an intensely proliferating tubularsystem in communication with the extracellular space,which therefore probably represents the developing transversetubular system. The segments also contained endocytosedmarker within large phagosomes. Contractile filamentsoccurred in the segments but were frequently lesswell-organized than in other parts of the myotubes. Thedescribed characteristics of the segments in rat myotubesdifferentiated in vitro bear resemblance to some of the characteristicsof the denervated endplate region of adult muscle.
|
|
| 19. |
- Tågerud, Sven, et al.
(författare)
-
Lysosomes in skeletal muscle following denervation. Time course of horseradish peroxidase uptake and increase of lysosomal enzymes
- 1984
-
Ingår i: Cell and Tissue Research. - 0302-766X .- 1432-0878. ; 236:1, s. 73-79
-
Tidskriftsartikel (refereegranskat)abstract
- The in-vivo uptake of exogenously applied horseradishperoxidase and the activities of the lysosomal enzymesacid phosphatase and cathepsin D were studied histochemicallyand/or biochemically in innervated and2-14 day-denervated tibialis anterior muscles of the mouse.The biochemically determined uptake of horseradish peroxidaseshowed a large increase already 4 days after denervation.The activities of the lysosomal enzymes increased ina more gradual fashion, and only cathepsin D showed anincrease in activity when expressed as total activity per muscle.Histochemically horseradish peroxidase was found tobe localized in muscle fibres in characteristic spindle-shapedsegments after denervation. The main increase in thenumber of such segments per transverse section of the muscleoccurred between 3 and 6 days after denervation. Inserial sections these segments frequently showed positivestaining also for acid phosphatase.It is concluded that exogenously applied horseradishperoxidase is taken up into the lysosomal system, whichafter denervation becomes organized into characteristicspindle-shaped segments in the muscle fibres. The endocyticactivity of muscle fibres increases early after denervation.This is followed by a more gradual increase in activity oflysosomal enzymes and finally by an organization of thelysosomal system into characteristic spindle-shaped segments.The results are compatible with the working hypothesisthat increased endocytosis may initiate lysosomal activationin denervated skeletal muscle.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Tågerud, Sven, et al.
(författare)
-
Receptor-mediated uptake of horseradish peroxidase in innervated and denervated skeletal muscle
- 1985
-
Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 160:1, s. 95-105
-
Tidskriftsartikel (refereegranskat)abstract
- The in vitro uptake of [3H]inulin and horseradish peroxidase (HRP) has been studied in innervated and 6 days denervated extensor digitorum longus muscle of the mouse. Both markers were taken up at a higher rate in denervated muscle. The increase in uptake after denervation was, however, larger for HRP than for [3H]inulin. After 2 h incubation at 37 °C, pH 7.3, in the presence of equimolar concentrations of HRP and [3H]inulin (approx. 2.1 μM), the uptake of HRP was approx. 8 times as great as the uptake of [3H]inulin in the same innervated muscles. In denervated muscle the HRP uptake was approx. 19 times as great as the [3H]inulin uptake in the same muscles. Various possible explanations of these differences in uptake have been considered and tested experimentally. [3H]Inulin uptake in skeletal muscle has previously been shown to obey bulk kinetics. The present investigation shows the HRP uptake to obey saturation kinetics. The HRP uptake shows dependency on divalent cations and is reduced if incubation is carried out at pH 6.4. The uptake of HRP, when used at a low, non-saturating concentration (10 μg/ml approx. 0.25 μM), is inhibited 60% by yeast mannan (0.1 mg/ml), ribonuclease B (0.1 mg/ml, approx. 7.4 μM), mannose (30 mM), monodansylcadaverine (1 mM), chloroquine (100 μM), trifluoperazine (25 μM) or maleic acid (2 mM). It is concluded that HRP is taken up in innervated and denervated skeletal muscle by a process of receptor-mediated endocytosis and that this uptake is under neurotrophic control.
|
|
| 23. |
- Tågerud, Sven, et al.
(författare)
-
The nifk gene is widely expressed in mouse tissues and is up-regulated in denervated hind limb muscle
- 2003
-
Ingår i: Cell Biology International. - 1065-6995 .- 1095-8355. ; 27:6, s. 469-475
-
Tidskriftsartikel (refereegranskat)abstract
- Denervation of skeletal muscle alters the expression of many genes, which may be important for establishing optimal conditions for reinnervation. Using the differential display technique we have attempted to discover neurally regulated genes in skeletal muscle. An mRNA that is up-regulated in denervated hind limb muscle was identified and cloned. The cDNA encodes an RNA-binding protein, which was discovered during the course of this work to be a nucleolar protein interacting with the fork-head associated domain of the proliferation marker protein Ki-67, and named NIFK. We show that the nifk gene is widely expressed in adult mouse tissues and that the expression is up-regulated in denervated hind limb muscle. No difference between expression in perisynaptic and extrasynaptic portions of muscle was observed. The widespread expression in adult tissues suggests that the NIFK protein has other functions in addition to its interaction with Ki-67, which is only expressed in proliferating cells.
|
|
| 24. |
|
|
| 25. |
- Vult von Steyern, Fredrik, et al.
(författare)
-
Endocytotic activity of mouse skeletal muscle fibres after long-term denervation
- 1994
-
Ingår i: Journal of the Neurological Sciences. - 1878-5883. ; 125:2, s. 147-152
-
Tidskriftsartikel (refereegranskat)abstract
- The endocytotic activity of skeletal muscle fibres and its relation to the denervated endplate region has been studied using horseradish peroxidase (HRP) as marker for endocytosis. In muscles denervated for a short time period (10-20 days) HRP-uptake occurred in small segments of the muscle fibres near the centre of the muscle (endplate region). After long-term denervation (6-12 months) similar segments with high endocytotic activity were seen preferentially in more peripheral parts of the muscle fibres. Ultrastructural characteristics of segments with high endocytotic activity from long-term denervated muscle fibres include a proliferating transverse tubular system, HRP-containing bodies of different sizes with some very large vacuoles extending over several sarcomeres. These characteristics are similar to those described previously for HRP-uptake in the endplate region of short-term denervated muscle (Tagerud et al., J. Neurol. Sci., 75 (1986) 141) except that no recognizable endplate structures were observed in the present study. The results are discussed in relation to the fate of the denervated endplate and the receptive capacity for synapse formation in long-term denervated muscle.
|
|
