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  • 1
    ISSN: 1432-0533
    Keywords: Key words B-50(GAP-43) ; Spinal cord ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract B-50(GAP-43) is a phosphoprotein mainly found in the nervous system which plays a major role in neurite growth during development and regeneration as well as in synaptic remodelling. In the mature intact central nervous system, intense B-50 immunoreactivity (B-50-IR) can still be detected in regions which maintain residual capacity for structural re-organization. B-50 expression has been studied extensively in laboratory animals; however, its distribution and regulation in the human spinal cord is largely unknown. As a first step to analyze lesion-induced structural alterations, we investigated the distribution of B-50 protein and mRNA in the normal adult human spinal cord and dorsal root ganglia. Intense B-50-IR was localized to the superficial laminae of the dorsal horn at all segmental levels, the intermediolateral nucleus at thoracic levels and Onuf’s nucleus at sacral levels. Scattered neurons, particularly in the ventral horn of lumbar and sacral segmental levels (and occasionally also in Clarke’s nucleus) displayed intense B-50-IR in close apposition to the perikaryal and proximal dendritic surfaces. Nonradioactive in situ hybridization indicated that B-50 mRNA could also be detected in neurons of the ventral horn and also in the intermediolateral nucleus. The distribution of B-50 mRNA and protein in the normal human spinal cord shows a marked similarity to that reported in experimental animals, including the selective labelling of Onuf’s nucleus. However, the strong B-50-IR on the surface of some large anterior horn motor neurons has not been observed in other mammals. This finding might reflect a particular state of readiness for synaptic plasticity.
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  • 2
    ISSN: 1432-0533
    Keywords: Key words Zidovudine ; Myopathy ; Nucleus ; Mitochondria ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term zidovudine (also termed azidothymidine, AZT) treatment of AIDS patients may cause severe myopathy characterized by conspicuous mitochondrial and nuclear changes. The mitochondrial changes are attributed to an inhibitory effect of AZT on the mitochondrial γ-polymerase in a variety of cells. Inhibition of the nuclear α-polymerase is another well-known side effect of AZT, whereas the (nuclear) β-polymerase appears to be rather insensitive. The nuclear changes seen in AIDS patients are usually considered secondary to the human immunodeficiency virus infection. To eliminate the influence of the virus on the nuclei, we studied the effect of AZT on non-infected, organotypic co-cultures of spinal ganglia, spinal cord, and skeletal muscle from fetal rats. We noted significant changes not only in the mitochondria but also in the nuclei of spinal ganglia, spinal cord, and muscle cells, which depended more on the duration of AZT application (1, 3, 5, and 8 days) than on the concentration (0.1, 1, 10, 100 and 1000 μM). The alterations of the mitochondria consisted mainly of swelling, loss of cristae and, finally, disappearance. The nuclei showed nucleolar segregation, marginal condensation of heterochromatin, formation of interchromatin and perichromatin granules, nuclear protrusions and pseudoinclusions and, finally, disintegration. The changes were not as pleomorphic as those seen in biopsy specimens from AIDS patients who had received long-term treatment with AZT. However, this difference can easily be attributed to the short duration of drug application in tissue culture compared to the long-term medication in patients.
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  • 3
    ISSN: 1432-0533
    Keywords: Zidovudine ; Myopathy ; Nucleus ; Mitochondria ; AIDS
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Zidovudine (formerly azidothymidine) is a potent inhibitor of the human immunodeficiency virus (HIV) reverse transcriptase and represents the first approved drug showing clinical efficacy in HIV-associated diseases. However, considerable toxicity causing macrocytic anemia, neutropenia, and myopathy has been reported, with severe mitochondrial alterations as a special feature of this myopathy. The mitochondrial changes are consistent with the fact that zidovudine acts as an inhibitor of the mitochondrial gamma-polymerase. Electron microscopically, we could confirm the presence of severely altered mitochondria in a 32-year-old male, who developed a necrotizing myopathy after daily administration of 1,000 mg zidovudine over a period of 15 months. In addition, there were even more severe nuclear changes that, for the most part, have not been documented electron microscopically in HIV-related myopathy either with or without zidovudine treatment, especially in non-necrotic and non-regenerating fibers. Since various in vitro studies have shown interference of zidovudine with nuclear DNA metabolism even in human cell lines, we assume that the nuclear changes that we observed are at least in part related to zidovudine treatment.
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  • 4
    ISSN: 1432-0533
    Keywords: Muscle spindle ; Denervation ; Reinnervation ; Muscle fiber atrophy ; Mitochondria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structure of normal, denervated, and reinnervated muscle spindles in lower lumbrical muscles of rats was studied morphometrically at time intervals ranging from 3–14 months. In control spindles, the mean transverse area of mitochondria was estimated to be more than twice as large in nuclear chain than in typical nuclear bag fibers. Following denervation, there was a severe decrease of the mean number and transverse area of mitochondria, and a moderate, but statistically significant decrease of the mean transverse area of intrafusal muscle fibers (IMFs) despite an increase of the number of IMFs. At 12–14 months of reinnervation, changes of the transverse areas of IMFs were statistically insignificant, but the mean values for the mitochondria were incompletely restored. At 4×3 months, after fourfold repeated crush injuries to the nerve, most of the values estimated (transverse area of mitochondria; number, shape, and transverse area of IMFs and nuclei) tended to approach those in denervated rather than in reinnervated IMFs. The differences of the reactions of intra- and extrafusal muscle fibers following complete motor and sensory denervation appeared to be in accordance with their normal dimensional dissimilarities.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 16 (1970), S. 324-341 
    ISSN: 1432-0533
    Keywords: Spinal Cord ; Spinal Ganglia ; Neuromuscular Spindles ; Mitochondria ; Isoniazid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Entgegen anderslautender Angaben in der Literatur werden bei der INH-Neuropathie auch die sensorischen Nervenendigungen in den Muskelspindeln betroffen. Die Veränderungen bestehen in einem Verlust der synaptischen Vesikel, in Mitochondrienschwellungen und-Verdichtungserscheinungen, in terminalen Axonfragmentationen und Reaktionen der zugehörigen intrafusalen Muskelfasern. Außerdem lassen sich schon in frühesten Stadium der INH-Neuropathie, am 4. Tag nach Beginn der INH-Applikation, Veränderungen in den lumbosacralen Spinalganglien und im Rückenmark nachweisen. Die Veränderungen in den Perikaryen gleichen denen bei der retrograden Zellveränderung weitgehend. Über die Spezifität der Alterationen an den sensorischen Nervenendigungen ist vorest keine sichere Aussage möglich, da vergleichbare Untersuchungen über pathologisch veränderte Muskelspindeln, insbesondere nach der einfachen Durchschneidung des Nerven, bisher fehlen.
    Notes: Summary In INH-neuropathy sensory nerve endings of distal muscle spindles may be severely altered. The changes are characterized by a disappearance of synaptic vesicles, mitochondrial swelling or condensation, fragmentation of axon terminals and reactions of the corresponding intrafusal muscle fibers. Also, occasional alterations in lumbosacral spinal ganglia and spinal cord were seen occurring already in the initial stage of INH-neuropathy at the 4th day after the beginning of INH application. The perikaryal changes resemble those of the retrograde cell reaction. Any specificness of the alterations seen in the sensory endings of muscle spindles cannot be ruled out at the present time since there are no comparable fine structural studies of pathological alterations in muscle spindles after simple nerve section or other nerve lesions.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 15 (1970), S. 156-175 
    ISSN: 1432-0533
    Keywords: Peripheral Nerve ; Nerve Degeneration ; Axon ; Mitochondria ; Isoniazid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im N. ischiadicus der Ratte kommen etwa doppelt so viele marklose als markhaltige Nervenfasern vor. Das normale zahlenmäßige Verhältnis dieser beiden Fasertypen schwankt in weiten Grenzen. Schon im ungeschädigten Nerven lassen sich bereits an einzelnen marklosen Nervenfasern verschiedenartige regressive Veränderungen wie Strukturverlust und perlschnurförmige Auftreibungen nachweisen; sie sind in der Regel von akuten, toxisch bedingten Veränderungen durch das Fehlen charakteristischer Schwann-Zellreaktionen zu differenzieren. Bei der INH-Neuropathie degenerieren anfangs im Verhältnis zu den markhaltigen nur wenige marklose Nervenfasern. Einige marklose Axone können unregelmäßig konturiert, geschwollen oder geschrumpft erscheinen; dabei lösen sich die Tubuli und Filamente auf; in manchen Fällen verdichtet sich ausch das Axolemm. Die Axonveränderungen werden von Störungen der normalen Axon-Schwann-Zellrelation begleitet. In den Anfangsstadien können manche Schwann-Zellen hochgradig deformiert sein; später verlieren sie ihre Oberflächendifferenzierung und runden sich (auf dem Querschnitt) ab. In der Regel zeigen die marklosen Nervenfasern bei der INH-Neuropathie die gleichen Veränderungen und Störungen der Axon-Schwann-Zellrelation wie bei der Wallerschen Degeneration. Extreme prolapsartige Verformungen von Axonen und Schwann-Zellen sowie mitochondriale Granula haben wir jedoch nur bei der INH-Neuropathie, nicht aber bei der Wallerschen Degeneration beobachtet.
    Notes: Summary In sciatic nerves of rats, there are more than twice as much unmyelinated than myelinated axons. Their ratio varies in a wide range from one area to the other. Some regressive changes are seen already in unmyelinated axons of normal controls (loss of structural components, axonal beading). Usually, these alterations can be distinguished from early experimental lesions by the lack of characteristic Schwann cell reactions. In the beginning of INH-neuropathy, fewer unmyelinated than myelinated nerve fibers are degenerating. Some of the unmyelinated axons may become irregularily folded, swollen, or shrunken while there is a progressive loss of tubules, filaments, normal mitochondria, and sometimes an increase in the thickness of the axolemma. The axonal changes are accompanied by a disturbance of the normal axon-Schwann cell relation. Initially, some Schwann cells may become extremely irregular; later they lose their surface differentiation while their cross sectional contour becomes rather rounded. In general, unmyelinated axons in INH-neuropathy show similar alterations and disturbances of the axon-Schwann cell relation as seen in Wallerian degeneration. Yet extremely deformed unmyelinated nerve fibers, axons as well as Schwann cells, and mitochondrial granules were only observed in INH-neuropathy.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 290 (1997), S. 31-37 
    ISSN: 1432-0878
    Keywords: Key words: Sural nerve ; Blood vessels ; Angiopathic neuropathy ; Vasculitis ; Peripheral neuropathy ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The number and dimensions of epineurial blood vessels in normal human sural nerves have, thus far, not been determined using systematic, reproducible morphometric methods, although this nerve is most frequently used for diagnostic biopsies. Quantitative changes in epineurial blood vessels appear to be major parameters for identifying angiopathy and angiopathic peripheral neuropathy. Therefore, we examined the epineurial blood-vessel number in relation to the age of the patients and to the number and size of the nerve fascicles in each of 51 human sural nerve biopsies. The data from a control group were compared with pathological cases. We found that the number of epineurial blood vessels (normal mean: 57.7) increased significantly (up to 196) in biopsies where there were signs of angiopathy (P≤0.01) or vasculitis (P≤0.05). The increase in the number of epineurial blood vessels usually resulted from a proliferation of capillaries. The fascicular cross-sectional area did not appear to be related to the number of epineurial blood vessels, although it increased significantly in cases with vasculitis (P≤0.05) or an axonal type of neuropathy (P≤0.05). Thus, this study shows that the number of epineurial blood vessels is a helpful parameter in verifying angiopathy and angiopathic peripheral neuropathy.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 273 (1993), S. 499-509 
    ISSN: 1432-0878
    Keywords: Ranvier's node ; Development ; Sural nerve ; Axon ; Myelin sheath ; Paranodal junctions ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Developmental alterations of paranodal fiber segments have not been investigated systematically in human nerve fibers at the light- and electron-microscopic level. We have therefore analyzed developmental changes in the fine structure of the paranode in 43 human sural nerves during the axonal growth period up to 5 years of age, and during the subsequent myelin development up to 20 years and thereafter. The nodal, internodal, and paranodal axon diameters reach their adult values at 4–5 years of age. The ratio between internodal and paranodal axon diameters remains constant at 1.8–2.0. Despite a considerable increase in myelin sheath thickness, the length of the paranodal myelin sheath attachment zone at the axon does not increase correspondingly, because of attenuation, separation from the axolemma, and piling up of myelin loops in the paranode. Separation of variable numbers of terminal myelin loops from the underlying axolemma results in the formation of bracelets of Nageotte, whereas the transverse bands of these loops disappear. The adaptation of the paranodal myelin sheath to axonal expansion during development probably occurs by uneven gliding of the paranodal myelin loops simultaneously with internodal slippage of myelin lamellae. Since mechanically stabilizing structures (tight junctions and desmosomes between adjacent paranodal myelin processes; transverse bands between myelin loops and paranodal axolemma) are unevenly arranged, especially during rapid axonal growth, paranodal axonal growth with simultaneous adaptation of the myelin sheath is probably discontinuous with time.
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