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  • Mitochondria  (5)
  • Neuropathy  (4)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 78 (1989), S. 649-661 
    ISSN: 1432-0533
    Keywords: Pyloric stenosis ; Myenteric plexus ; Smooth muscle ; Neuropathy ; Myopathic changes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The myenteric plexus and intramuscular nerve bundles in the circular muscle layer of the pylorus from 37 children with infantile hypertrophic pyloric stenosis (IHPS) obtained at pyloromyotomy were studied by light and electron microscopy and compared to six control cases without clinical evidence of IHPS. In certain IHPS cases degenerative alterations of the axons predominated. The axonal changes consisted of (1) severely increased variability of diameters with evidence of degeneration and regeneration of some axons, (2) accumulation of electron-dense bodies, lysosomes and pleomorphic membranous cytoplasmic bodies, (3) increase in the number of maloriented neurofilaments, and (4) aggregation of glycogen granules. Degenerative changes or immaturity of perikarya of neurons and glial cells in the myenteric plexus were not a significant feature. While axonal changes predominated in some IHPS cases there were severe changes of smooth muscle cells in others suggesting that a primarily neurogenic type of IHPS can be distinguished from a predominantly myogenic type. Although the etiology of the axonal changes in IHPS is not clear, it is suggested that they play an important role in the pathogenesis of pyloric stenosis and hypertrophy.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 80 (1990), S. 295-306 
    ISSN: 1432-0533
    Keywords: Pyloric stenosis ; Smooth muscle ; Myenteric plexus ; Visceral myopathy ; Neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Smooth muscle cell biopsies obtained at pyloromyotomy from 37 children with infantile hypertrophic pyloric stenosis (IHPS) were studied by light and electron microscopy and compared with 6 autopsy control cases without any clinical evidence of this disorder. In cases with IHPS an apparently irregular increase in the number of smooth muscle cells by mitosis was accompanied by an increase of the endoplasmic reticulum, proliferation of mitochondria and regressive changes, such as shrinkage, swelling, necrosis and apoptosis of smooth muscle cells. Other alterations, seen in some but not all cases consisted of large numbers of unusual dense granules some of which were clearly associated with actin filaments and, therefore, regarded as derivatives of the normally occurring dense bodies. Furthermore, intermyofibrillar and subsarcolemmal glycogen accumulations, various nuclear abnormalities and pleomorphic membranous cytoplasmic or nuclear bodies occurred. While smooth muscle cell abnormalities predominated in some cases of IHPS, in others there were more severe axonal changes in the myenteric plexus. It is suggested, therefore, that a primarily myogenic type of IHPS can be distinguished from a predominantly neurogenic type.
    Type of Medium: Electronic Resource
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 79 (1989), S. 190-199 
    ISSN: 1432-0533
    Keywords: Amyloidosis ; Neuropathy ; Immuno-electron microscopy ; Immunoglobulin light chains ; Perpheral nerve
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sural nerve specimens from ten patients with amyloidosis (hereditary, associated with lymphoproliferative disorders, or of unknown origin) and peripheral neuropathy were investigated by immunohistochemistry at the light and electron microscopic level. Peroxidase-antiperoxidase and immunogold techniques were applied to glutaraldehyde-fixed, osmicated and epoxy-embedded tissue. In five cases, four of which associated with lymphoproliferative disorders, amyloid deposits strongly and exclusively reacted with antibodies to kappa or lambda light chains, respectively. By electron microscopy, bundles of immunogold-labelled amyloid fibrils could be identified in coated and uncoated single membrane-bound vesicles of endoneurial macrophages. Schwann cells did not contain intracellular amyloid but their processes were entangled in amyloid fibrils and their basement membranes were sometimes fused with the fibrillar masses. It is concluded that immunoglobulin light chains in AL (amyloid of immunoglobulin light chain origin) amyloidosis precipitate, forming amyloid fibrils, in the presence of, and presumably with the assistence of, endoneurial cells. Inefficiency of phagocytosis appears to be one of the major causes for the deleterious effects of amyloid.
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  • 5
    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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  • 6
    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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  • 7
    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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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 65 (1985), S. 285-292 
    ISSN: 1432-0533
    Keywords: Thalidomide ; Neuropathy ; Conduction velocity ; Myelin sheath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Morphological studies of experimental thalidomide neuropathy have thus far failed to show any significant structural changes. The present investigation was performed on sural nerves of female New Zealand white rabbits showing a reduction of sensory conduction velocity after oral treatment with thalidomide (100 mg/kg b.wt. per day) for a period of 33 weeks. Rabbits of the same strain and equal sex, weight, and number served as controls. Very few nerve fibers were undergoing Wallerian degeneration in both groups, experimental animals and controls. Morphometry, however, revealed a statistically significant reduction of the mean myelin thickness of sural nerve fibers in the thalidomide group of rabbits as compared to controls. The mean myelin thickness of the largest nerve fibers was also significantly smaller than in the control group. On the other hand, axonal diameters were not significantly altered. The association between the decrease of the sensory conduction velocity, the reduction of the myelin sheath thickness, and the chronic thalidomide application is discussed.
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