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  • Polymer and Materials Science  (7)
  • Mitochondria  (5)
  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Bognor Regis [u.a.] : Wiley-Blackwell
    Journal of Polymer Science Part B: Polymer Physics 29 (1991), S. 1607-1612 
    ISSN: 0887-6266
    Keywords: neutron scattering (SANS) from hot stretched polystyrene ; polystyrene, hot stretched, SANS study of ; chain deformation in hot stretched polystyrene, SANS study of ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Small-angle neutron scattering (SANS) has been used to investigate macromolecular orientation of uniaxially hot-stretched partially deuterated polystyrene. Principle radii of gyration and degree of eccentricity were measured over a range of hot-stretch temperatures, strain rates, and external draw ratios (EDR). Results show affine deformation for EDR 〈4 and an increase in the degree of local molecular orientation with increasing rate of strain and decreasing stretching temperature. It also is found that although the macromolecules follow the external stretching affinely on average, they do not deform uniformly.
    Additional Material: 3 Ill.
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  • 7
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Chemie Ingenieur Technik - CIT 60 (1988), S. 152-153 
    ISSN: 0009-286X
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
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  • 8
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 39 (1998), S. 539-548 
    ISSN: 0021-9304
    Keywords: cytokine delivery via covalent binding ; tissue repair ; biomaterials ; collagen ; transforming growth factor β ; polyethylene glycol ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To overcome rapid diffusion and clearance from the implant site and to increase stability, recombinant transforming growth factor β2 (TGF-β2) was covalently bound to injectable bovine dermal fibrillar collagen (FC) and its activity compared to admixed TGF-β2. Covalent binding was achieved in a two-step procedure: First, TGF-β2 was reacted with the difunctional polyethylene glycol (PEG) linker, and then the PEG-attached TGF-β2 (PEG-TGF-β2) was bound to the fibrillar collagen (FC-PEG-TGF-β2). Initial binding of TGF-β2 to difunctional succinimidyl glutarate (D-SG-PEG) or succinimidyl propionate polyethylene glycol (D-SE-PEG) linkers was completed after reacting for 8 or 10 min as monitored by reverse-phase high-performance liquid chromatography. After reaction with injectable fibrillar collagen, extraction of unbound PEG-TGF-β2 and Western blot analysis, using a TGF-β specific antibody, demonstrated that at least 85% of the TGF-β2 was bound to the fibrillar collagen. The activity of PEG-TGF-β2 was fully stable in phosphate-buffered saline at 4°C and 37°C for at least up to 4 weeks. Unmodified TGF-β2 mixed with fibrillar collagen was completely inactivated after 1 week of incubation, as measured by the mink lung epithelial cell (Mv1Lu) growth inhibition assay. Formulations of FC-PEG-TGF-β2 containing 40 μg/mL TGF-β2 were implanted subcutaneously into rats and analyzed after days 7, 21, and 42. All TGF-β2-containing formulations showed the TGF-β typical fibroblastic response at the day 7 time point. Covalent binding of TGF-β2 to collagen with both difunctional PEG crosslinkers resulted in a significantly stronger and longer-lasting TGF-β2 response than that observed with admixed formulations of collagen and TGF-β. The TGF-β response with FC-PEG-TGF-β2 lasted up to day 42 but was not seen after day 7 for TGF-β2 admixed to FC. These findings clearly demonstrate that TGF-β2 remains fully active after being covalently bound to collagen via difunctional PEG. In addition, covalent binding potentiates and prolongs in vivo TGF-β responses and stabilizes the TGF-β in vitro. Results suggest that this method of formulation could be useful to stabilize and deliver similar peptide growth factors or biologically active agents. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 539-548, 1998.
    Additional Material: 10 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Polymer Science 47 (1960), S. 417-433 
    ISSN: 0022-3832
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Phosphorus trichloride and oxygen react readily with polyethylene to introduce phosphonic dichloride ( - POCl2) groups into the polymer (chlorophosphonation). Treatment of the resulting intermediate with water, alcohols, and amines yields polymeric alkylphosphonic acids, esters and amides, respectively. Derivatives containing as much as 16% phosphorus have been prepared. With increasing degree of phosphonation, polyethylene crystallinity is reduced, the acid and amide derivatives become stiffer, less extensible, and less soluble in nonpolar solvents, and internal plasticization is observed in the ester derivatives. No significant decrease in flammability is effected by phosphonation unless chlorine is introduced also. The ester and amide derivatives crosslink under mild conditions by an unknown mechanism, the acid derivative will crosslink on heating with litharge. The chlorophosphonation reaction is sensitive to inhibitors and no highly active catalyst was found. The rate appears to be governed by the rate at which oxygen dissolves in the mixture. Substitution of air or chlorine for oxygen, phenyldichlorophosphine or diphenylchlorophosphine for phosphorus trichloride results in introduction of phosphorus-containing groups into polyethylene, also, but at reduced rates. In sharp contrast to polyethylene's apparent stability toward the phosphonation conditions, polystyrene, poly(methyl methacrylate), and polyisobutylene undergo a rapid decrease in molecular weight on treatment with phosphorus trichloride and oxygen. The fact that these four polymers exhibit the same relative behavior, i.e., polyethylene is stable whereas the other three polymers are unstable, in various free radical processes argues for a free radical mechanism in the chlorophosphonation reaction.
    Additional Material: 8 Tab.
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  • 10
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Polymer Science 46 (1960), S. 547-550 
    ISSN: 0022-3832
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Additional Material: 1 Ill.
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