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  • 1
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] SIL1 (also called BAP) acts as a nucleotide exchange factor for the Hsp70 chaperone BiP (also called GRP78), which is a key regulator of the main functions of the endoplasmic reticulum. We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sjögren ...
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  • 2
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] We report missense mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) in seven large pedigrees affected with Charcot-Marie-Tooth neuropathy type 2A (CMT2A). Although a mutation in kinesin family member 1B-β (KIF1B) was associated with CMT2A in a single Japanese family, we ...
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  • 3
    ISSN: 1432-2307
    Keywords: Muscle spindle ; Elastic fibres ; Elaunin fibres ; Oxytalan fibres ; Denervation ; Reinnervation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Muscle spindles in the lower lumbrical muscles of rats were studied by transmission electron microscopy following denervation with or without reinnervation. The number and total area of elastic fibres per muscle spindle increased at 3–12 months following various experimental procedures: (1) denervation and reinnervation after a single crush lesion to the sciatic nerve; (2) reinnervation after four-fold repeated crush injuries; and (3) transection and suture of the nerve. The increased number of oxytalan and elaunin fibres, the precursors of mature elastic fibres, within these muscle spindles provided further evidence for their numerical and dimensional increase. An attachment site of elastic fibres at the spindle pole was identified at the inner cells of the outer spindle capsule. The processes of these cells embraced terminating elastic fibres tightly. Attachment of elastic fibres to intrafusal muscle fibres was less conspicuous since they were not similarly embraced but were rather indistinctly, though closely, associated with the basal lamina along longitudinal surface indentations of intrafusal muscle fibres. It is concluded from this series of experiments that muscle spindles, as dynamic mechanoreceptors, maintain their elastic properties even under pathological conditions. The increase of elastic fibres following denervation and reinnervation represents an obviously meaningful reaction that may compensate for loss of tonic properties of muscle spindles without causing stiffness.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 432 (1998), S. 199-205 
    ISSN: 1432-2307
    Keywords: Key words Nerve biopsy ; Sural nerve ; Peripheral neuropathy ; Skin biopsy ; Fixation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Peripheral nerve biopsy is now an established, valuable investigative procedure, but as it can give rise to significant residual symptoms it should only be undertaken after careful consideration of the indications and with informed consent from the patient. Nerve biopsies should only be processed and evaluated in a laboratory with the relevant particular expertise. It is generally recommended that a sural nerve biopsy be performed in combination with a muscle biopsy but not vice versa (muscle biopsies together with a nerve biopsy). Nerve biopsy is not the only means of sampling peripheral nerve tissue to study the peripheral nervous system. Examination of the innervation of the skin may be informative. The same is likely to be true for motor point muscle biopsy. Nerve biopsy is mainly used for morphology although molecular genetic techniques using fresh or archival nerve biopsies are increasingly available. Chemical analysis is undertaken mainly for research purposes.
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  • 5
    ISSN: 1432-0533
    Keywords: HLA-DR ; Neuropathies ; Macrophages Fibroblasts ; Schwann cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of HLA-DR and the macrophage marker CD 68 was studied in 44 sural nerve biopsies from patients with inflammatory and non-inflammatory neuropathies and controls using immunohistochemistry on non-osmicated semithin sections, a technique that has not been used before in such a biopsy study. Most HLA-DR-immunoreactive (ir) cells were fibroblasts, macrophages on perineurial cells, some were perivascular and endothelial cells, and only few were Schwann cells. Counts of immunoreactive cells revealed (a) increased HLA-DR expression in severe as compared to less severe neuropathies and to controls, (b) no correlation between the numbers of HLA-DR-ir cells and CD 68-ir macrophages, and (c) no close correlation between diagnostic groups and the number of HLA-DR-ir cells, but higher numbers in inflammatory neuropathies. We conclude that endoneurial fibroblasts and macrophages as antigen-presenting cells may be mediators in various peripheral nerve diseases, not only in inflammatory disorders.
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  • 6
    ISSN: 1432-0533
    Keywords: Perineurial cells ; Nerve regeneration ; Immunohistochemistry ; Epithelial membrane antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Perineurial cells are specialized connective tissue cells that form a barrier between endoneurium and epineurium in normal nerves. In the present study, the formation of the perineurium after transection of rat sciatic nerves was investigated. The cord bridging the gap between proximal and distal stumps through silicone tubes was studied 3, 7, 12, 18, and 21 days after surgery using electron microscopy and antibodies against epithelial membrane antigen (EMA), a marker for perineurial cells that has thus far not been applied to the study of differentiating cells in nerve tubulation systems. Initially, a thin cord consisting of fibrin bridged the gap between the stumps. At 7 days, longitudinal cells had migrated from both stumps toward the center of the tubes on the surface of the fibrin cord. These cells were immunoreactive with anti-EMA. At 12 days, ultrastructural features of perineurial cells (desmosomes, tight junctions, actin filaments with dense bodies, tonofilaments) were prominent in these cells. Subsequently, the gap was bridged through the perineurial tube by endothelial cells, pericytes, fibroblasts, Schwann cells, and axons. At 21 days, a single large nerve fascicle ensheathed by a mature perineurium was found between the stumps. Thus, the first cells to connect proximal and distal stumps in the investigated nerve regeneration silicon chamber system are perineurial cells. Through the tube formed by these cells, blood vessels and nerve fibers bridge the gap. Therefore, establishment of a perineurial connection between nerve stumps appears to be important in the sequence of events during nerve regeneration.
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  • 7
    ISSN: 1432-0533
    Keywords: Thalidomide ; Wallerian degeneration ; Schwann cell proliferation ; Immune inhibition ; Endoneurial edema
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In addition to the well-known teratogenic effect of thalidomide, previous studies have revealed mild immunosuppressive properties and, more recently, and antiangiogenic activity. To find out more about the specificity of these effects we studied the influence of orally administered thalidomide on Wallerian degeneration in rats. Wallerian degeneration is a potent experimental model for studying reproducible cell proliferation in vivo. Examination of distal nerve segments of transected sciatic nerves from rats that had been treated with thalidomide (2×250 mg/kg per day) revealed a significant reduction of endoneurial cell counts at 10–15 days after surgery compared to that seen in controls. This effect was not statistically significant, at a very early stage of Wallerian degeneration, i.e., at 5 days after transection of the nerve. Subperineurial edema and phagocytosis was also reduced, although this was not statistically significant. This apparently nonspecific inhibitory effect of thalidomide during early Wallerian degeneration shown in the present study should be investigated further for its possible relationship to other previously established inhibitory activities of thalidomide, especially its immunosuppressive effect in man.
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  • 8
    ISSN: 1432-0533
    Keywords: Cerebral autosomal dominant arteriopathy Immunoglobulin deposits ; Peripheral neuropathy ; Sural nerve biopsy ; Small vessel disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy' (CADASIL) has recently been identified as a hereditary disorder with characteristic fine structural changes of small intracerebral arteries and arterioles. Electron microscopically there are characteristic perivascular deposits of granular electron-dense material resembling immunoglobulin deposits. The present case from a family with four affected members in three successive generations shows that similar vascular changes as described in the central nervous system are present in blood vessels of the sural nerve, although less pronounced and, therefore, affording electron microscopy for their unequivocal detection. Nevertheless it has been shown for the first time that the diagnosis of CADASIL can be verified by a sural nerve biopsy. Occasional focal accumulation of pinocytotic vesicles opposite the granular deposits suggests exocytosis as one of the possible pathomechanisms for their production.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 30 (1974), S. 109-128 
    ISSN: 1432-0533
    Keywords: Muscle Spindle ; Muscle Pathology ; Muscular Atrophy ; Muscle Denervation ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Reinnervated muscle spindles in lower lumbrical muscles of rats studied 17 days to 24 months after crushing the sciatic nerve showed a series of alterations which have not been analysed, thus far, by electron microscopy. There was a striking increase of the number of intrafusal muscle fibers seen in approximately 20% of reinnervated spindles. These spindles showed 5–11 intrafusal muscle fibers whereas normal spindles usually contained 3–4 fibers only. New intrafusal muscle fibers originated by splitting from pre-existing ones, or by maturation from satellite cells which were numerous in normal as well as in reinnervated spindles. The increase of the number of intrafusal muscle fibers was caused by denervation rather than reinnervation since a similar increase in the number of intrafusal muscle fibers was also seen in some denervated spindles after prevention of reinnervation. An additional proliferation of intrafusal Schwann cells resulted from Wallerian degeneration of intrafusal nerve fibers. Dense bodies and flecked vesicles were repeatedly noted in intrafusal muscle fibers. Myofibrillar abnormalities were present in some newly formed muscle fibers late after the lesion. Atrophy of intrafusal muscle fibers was rarely encountered. Atrophic fibers were filled with flecked vesicles or small mitochondria. ‘Hypertrophy’ of intrafusal muscle fibers was suggestive in only two fibers of 125 reinnervated muscle spindles. It could not be exclded that ‘hypertrophy’ resulted from erroneous alpha- or beta-motor innervation of intrafusal muscle fibers by aberrant regeneration of nerve fibers normally innervating extrafusal muscle fibers. Most reinnervated spindles, however, had a normal appearance in the plane of section studied.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 30 (1974), S. 129-144 
    ISSN: 1432-0533
    Keywords: Muscle Spindle ; Muscle Pathology ; Muscular Atrophy ; Muscle Denervation ; Regeneration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sensory and motor nerve endings in lower lumbrical muscles of rats were surprisingly well reconstituted following a single crush lesion of the sciatic nerve. No motor nerve endings were noted in the equatorial region, nor sensory endings in the polar regions of the muscle spindles examined. 1 and 2 months after the lesion, multiple axonal sprouts reinnervated an increased number of intrafusal Schwann cells and, occasionally, of intrafusal muscle fibers. This frequently resulted in abnormal contact relationships between multiple Schwann cell processes and muscle fibers, nerve terminals and muscle fibers, and nerve terminals and Schwann cell processes. In addition, the remaining or newly formed basement membranes of the respective Schwann cells, axons, or muscle fibers were often irregularly arranged. Freely floating basement membranes adjacent to intrafusal muscle fibers of Schwann cells were more frequently observed than in normal spindles. The internal structure of regenerated nerve terminals varied considerably; however, there was a wide range of variability in the structure of normal nerve terminals too. Most endings, at 14 and 24 months after the lesion, had a normal appearance although some altered relations between nerve terminals and muscle, fibers were still present. Some proliferated Schwann cells or Schwann cell processes as well as basement membranes were not reinnervated. These could represent the only evidence of the preceding lesion.
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