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  • 1
    Electronic Resource
    Electronic Resource
    Induction of the morphologic changes of both acute and chronic experimental myasthenia by monoclonal antibody directed against acetylcholine receptor (1984)
    Springer
    Acta neuropathologica 63 (1984), S. 131-143 
    Details
    ISSN: 1432-0533
    Keywords: Anti-acetylcholine receptor antibody ; Experimental autoimmune myasthenia gravis ; Monoclonal antibody ; Myasthenia gravis ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To investigate pathogenic mechanisms in experimental autoimmune myasthenia gravis (EAMG) and myasthenia gravis (MG), we studied the acute and chronic effects in rats of injection of rat monoclonal antibodies (MCABs) directed against the acetylcholine receptor (AChR). Animals were severely weak 12 h after a single injection, at which time macrophages were found invading endplate regions of muscle and cholinesterase-stained regions were separted from the underlying muscle fibers. Ultrastructural studies showed findings identical to the acute phase of EAMG: degenerating postsynaptic membranes and invasion and phagocytosis of endplate regions by macrophages. Animals receiving sublethal doses of MCAB recovered clinically by 4–5 days after injection. Recovery was accompanied by a progressive decrease in the number of macrophages associated with endplates and reapposition to the myofibers of the cholinesterasestained regions. Animals injected once, or repeatedly over several months, remained clinically and electromyographically normal after recovery from the initial episode of weakness, but their endplate ultrastructure was highly simplified with blunted or absent synaptic folds and shallow or absent secondary synaptic clefts. These studies demonstrate that anti-AChR MCABs can induce the changes of both acute and chronic EAMG. There is good correlation between the inflammatory changes and the acute clinical disease but poor correlation between morphological and clinical parameters in the chronic syndrome. The latter observation suggests that severe ultrastructural changes, similar to those seen in chronic EAMG and MG, cannot account, at least in rats, for the clinical and electrophysiologic abnormalities of MG.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00697195
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    A comparative study between cosolvent and cononsolvent ternary polymer systems through the preferential adsorption coefficient (1993)
    Springer
    Colloid & polymer science 271 (1993), S. 30-37 
    Details
    ISSN: 1435-1536
    Keywords: Ternary polymeric systems ; preferential adsorption coefficient ; cosolvent ; cononsolvent ; ternary interactions ; excess free energy ; intensity light scattering
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Sorption equilibrium of polystyrene and poly (dimethyl siloxane) in mixed solvents has been monitored by means of the preferential adsorption coefficient experimentally determined from intensity light scattering measurements. The pairs of solvents used to dissolve each polymer sample have been selected for the purpose to perform cosolvent and cononsolvent ternary polymer systems. Flory-Huggins formalism including ternary interactions has been used to predict the sorption equilibrium for the cosolvent system and, for the first time, for cononsolvent ones. Moreover, the proportionality between binary and ternary interactions, recognized by Pouchly, is also corroborated for both ternary polymer systems. From a thermodynamic standpoint, the sorption equilibrium has been described by approaching the behavior of the “bulk solvent” to the binary liquid mixture through the excess Gibbs free energy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00652300
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Viscometric behaviour of polymer blends based on poly (vinylidene fluoride) (1994)
    Springer
    Colloid & polymer science 272 (1994), S. 497-503 
    Details
    ISSN: 1435-1536
    Keywords: Poly(vinylidene fluoride) ; intrinsic viscosity ; polymer blood compatibility ; polymer-solvent inteaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The viscosity behaviour of dilute dimethylformamide solutions of poly(vinylidene fluoride)-poly (methyl methacrylate) and poly(vinylidene fluoride)-polystyrene has been studied at 25°C. The polymer concentration ranges are such that neither phase separation nor microgel formation occurs, although we are very close to theta conditions. The intrinsic viscosity and viscosity interaction parameter of the ternary mixtures have been calculated. The estimation of the compatibility of the above polymer pairs has been studied based on: a) specific viscosities; b) viscosity interaction parameters, according to Krigbaum and Wall formalism, and c) viscosity interaction parameters of a system formed by a dilute probe polymer in the presence of a matrix polymer and a small molecule solvent.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00653213
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  • 4
    Electronic Resource
    Electronic Resource
    Correlation between transport and equilibrium properties through the ternary interaction parameter for cosolvent and cononsolvent polymeric systems (1992)
    Springer
    Colloid & polymer science 270 (1992), S. 197-206 
    Details
    ISSN: 1435-1536
    Keywords: Ternarypolymericsystems ; secondvirialcoefficient ; intrinsicviscosity ; excessGibbsenergy ; cosolvent ; cononsolvent ; ternaryinteractionparameter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract A study of the ternary polymer systems dimethyl formamide-ethyl acetate-polystyrene, chloroform-1,4 dioxane-polystyrene and tetrahydrofuran-chloroform-polystyrene was carried out by viscosity and light scattering at 298 K. A good correlation has been found between the excess intrinsic viscosity, unperturbed polymer dimensions, second virial coefficient and the excess Gibbs free energy by using a ternary interaction parameter, dependent on molecular weight. This modification enables the conversion between transport and equilibrium properties.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00655470
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  • 5
    Electronic Resource
    Electronic Resource
    Prediction of maxima and minima in the curve of total sorption parameter in ternary polymer systems. Influence of ternary interaction parameter (1993)
    Springer
    Colloid & polymer science 271 (1993), S. 372-379 
    Details
    ISSN: 1435-1536
    Keywords: Ternary polymer systems ; extrema thermodynamic behavior ; total sorption parameter ; Flory-Huggins theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract Flory-Huggins theory modified by Pouchly has been applied to predict maxima and minima in the curve of total sorption in ternary polymer systems formed by a polymer and two liquids. In this work, different diagrams based on experimental magnitudes easily obtained such as the difference in affinities of liquids, solvents and non solvents, and the solvent molar volume ratio. Total sorption parameter has been considered to be the decisive magnitude to define extrema conditions in both cosolvent and cononsolvent ternary polymer systems. The theoretical prediction is not altered by the inclusion of ternary interactions. Different examples of ternary systems dealing with vinyl polymers and polydimethyl siloxane have been used to test the above formalism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00657418
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  • 6
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    A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity and increased susceptibility to proteostatic insult (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-07
    Description: The autosomal dominant spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of disorders exhibiting cerebellar atrophy and Purkinje cell degeneration whose subtypes arise from 31 distinct genetic loci. Our group previously published the locus for SCA26 on chromosome 19p13.3. In this study, we performed targeted deep sequencing of the critical interval in order to identify candidate causative variants in individuals from the SCA26 family. We identified a single variant that co-segregates with the disease phenotype that produces a single amino acid substitution in eukaryotic elongation factor 2. This substitution, P596H, sits in a domain critical for maintaining reading frame during translation. The yeast equivalent, P580H EF2, demonstrated impaired translocation, detected as an increased rate of –1 programmed ribosomal frameshift read-through in a dual-luciferase assay for observing translational recoding. This substitution also results in a greater susceptibility to proteostatic disruption, as evidenced by a more robust activation of a reporter gene driven by unfolded protein response activation upon challenge with dithiothreitol or heat shock in our yeast model system. Our results present a compelling candidate mutation and mechanism for the pathogenesis of SCA26 and further support the role of proteostatic disruption in neurodegenerative diseases.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Selective inhibition of caspases in skeletal muscle reverses the apoptotic synaptic degeneration in slow-channel myasthenic syndrome (2013)
    Oxford University Press
    Details
    Publication Date: 2013-12-11
    Description: Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca 2+ overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgenic mouse models for SCS (mSCS), the endplate regions are shrunken, and there is evidence of DNA damage in the subsynaptic region. Activated caspase-9, -3 and -7 are intensely co-localized at the NMJ, and the Ca 2+ -activated protease, calpain, and the atypical cyclin-dependent kinase (Cdk5) are overactivated in mSCS. Thus, the true mediator(s) of the disease process is not clear. Here, we demonstrate that selective inhibition of effector caspases, caspase-3 and -7, or initiator caspase, caspase-9, in limb muscle in vivo by localized expression of recombinant inhibitor proteins dramatically decreases subsynaptic DNA damage, increases endplate area and improves ultrastructural abnormalities in SCS transgenic mice. Calpain and Cdk5 are not affected by this treatment. On the other hand, inhibition of Cdk5 by expression of a dominant-negative form of Cdk5 has no effect on the degeneration. Together with previous studies, these results indicate that focal activation of caspase activity at the NMJ is the principal pathological process responsible for the synaptic apoptosis in SCS. Thus, treatments that reduce muscle caspase activity are likely to be of benefit for SCS patients.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    DnaJ-1 and karyopherin {alpha}3 suppress degeneration in a new Drosophila model of Spinocerebellar Ataxia Type 6 (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-07
    Description: Spinocerebellar ataxia type 6 (SCA6) belongs to the family of CAG/polyglutamine (polyQ)-dependent neurodegenerative disorders. SCA6 is caused by abnormal expansion in a CAG trinucleotide repeat within exon 47 of CACNA1A , a bicistronic gene that encodes α1A, a P/Q-type calcium channel subunit and a C-terminal protein, termed α1ACT. Expansion of the CAG/polyQ region of CACNA1A occurs within α1ACT and leads to ataxia. There are few animal models of SCA6. Here, we describe the generation and characterization of the first Drosophila melanogaster models of SCA6, which express the entire human α1ACT protein with a normal or expanded polyQ. The polyQ-expanded version of α1ACT recapitulates the progressively degenerative nature of SCA6 when expressed in various fly tissues and the presence of densely staining aggregates. Additional studies identify the co-chaperone DnaJ-1 as a potential therapeutic target for SCA6. Expression of DnaJ-1 potently suppresses α1ACT-dependent degeneration and lethality, concomitant with decreased aggregation and reduced nuclear localization of the pathogenic protein. Mutating the nuclear importer karyopherin α3 also leads to reduced toxicity from pathogenic α1ACT. Little is known about the steps leading to degeneration in SCA6 and the means to protect neurons in this disease are lacking. Invertebrate animal models of SCA6 can expand our understanding of molecular sequelae related to degeneration in this disorder and lead to the rapid identification of cellular components that can be targeted to treat it.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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