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  • 1
    ISSN: 1432-0533
    Keywords: Amyloid ; Alzheimers disease ; Scrapie ; EM ; Isolation ; Gerstmann-Sträussler syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The structure of partially purified, CNS amyloid fibrils from three different sources have been compared by negative stain EM. The fibrils isolated from brains with senile dementia of Alzheimer type were 4–8 nm in diameter, narrowing every 30–40 nm and apparently composed of two 2–4 nm filaments. The fibrils from a Gerstmann-Sträussler syndrome brain were 7–9 nm in diameter, narrowing every 70–80 nm and with a suggestion that they are composed of two 3–5 nm filaments. The fibrils isolated from 87V scrapie-affected mouse brains were 4–8 nm in diameter with a twist every 15–25 nm presumably composed of two 2–4 nm filaments. The fibrils from the scrapie brains were usually observed in pairs. The shape of the clusters of the isolated amyloid fibrils observed in each disease was similar in negative stain and thin section EM preparations and was related to the characteristic morphology of the amyloid fibrils in the neuritic and amyloid plaques in situ. The structural differences between the CNS amyloid fibrils from the various diseases studied by us may reflect differences in the polypeptides which comprise the fibril and/or a different pathogenesis in the formation of the amyloid fibrils.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0533
    Keywords: Alzheimer amyloids ; Synthetic peptide ; Antibodies ; Fibril formation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An antibody was raised to a synthetic peptide corresponding to a published sequence for the first 24 residues of a cerebrovascular amyloid peptide (CVAP). Immunohistochemical staining of tissue sections revealed that the antibody bound extensively to cerebrovascular amyloid in Alzheimer disease (AD/SDAT) and Down's syndrome cases. The antibody bound less extensively to neuritic plaques (primitive and mature) and indetectably to neurofibrillary tangles. The antibody did not label scrapie plaques, scrapie-associated fibrils, or Gerstmann-Sträussler syndrome plaques. Immunoblotting experiments showed that the cerebrovascular amyloid peptide epitopes contaminating the neurofibrillary tangle preparations could be extracted with urea, leaving the neurofibrillary tangles intact. These data confirm that the cerebrovascular amyloid peptide is a component of cerebrovascular amyloid, and suggest that its epitopes are also components of neuritic plaque amyloid. The reduced level of immunostaining on amyloid cores in tissue sections suggests that either the cerebrovascular amyloid peptide epitopes are a minor component of amyloid cores, or that their mode of packing or state of processing in amyloid cores renders them relatively inaccessible to the antibody. We also conclude that the cerebrovascular amyloid peptide is not a component of neurofibrillary tangles. The synthetic cerebrovascular amyloid peptide possesses amyloid-like properties: at neutral pH it forms insoluble aggregates consisting of 5–7-nm fibrils, which form red-green birefringent adducts with Congo red and fluoresce with thioflavine S.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0533
    Keywords: Alzheimer disease/senile dementia of the Alzheimer type ; Neurofibrillary tangles ; Paired helical filaments ; Intermediate filaments ; Neurofibrous proteins ; Cytoskeleton
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A method has been developed for the bulk isolation of Alzheimer neurofibrillary tangles (ANT) of paired helical filaments (PHF) from histopathologically confirmed cases of Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). The fresh or frozen autopsied cerebral cortex affected with Alzheimer neurofibrillary changes is dissociated by homogenization and sieving through nylon bolting cloth and the ANT are separated by a combination of sucrose discontinuous density gradient centrifugation, glass bead column chromatography, and sodium dodecyl sulfate (SDS) treatment. The isolated ANT produce red-green birefringence when viewed through polarized light after staining with Congo red. Ultrastructurally, the isolated PHF are well preserved and have the dimensions of the PHF seen in situ. Two major Populations of ANT which exist in different proportions in AD/SDAT brains are identified on the basis of their solubility in SDS. The ANT I and the ANT II are soluble and insoluble respectively on treatment with 2% SDS at room temperature for 5 min. Solubilization of the ANT II requires several repeated extractions with a solution containing 10% each of SDS and β-mercaptoethanol (BME) at 100°C for 10 min. Sonication of the ANT II greatly facilitates their solubilization. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the isolated ANT reveals the presence of two major polypeptides with molecular weights (MW) of 62,000 and 57,000, several minor polypeptides with MW below 57,000, and a significant amount of material not entering the stacking and the resolving gels. Re-electrophoresis of polypeptides extracted from various areas of the resolving gel or of the material which does not enter the gel generates the same polypeptide profile as on the first gel, suggesting that the PHF material which does not enter the gel may result from the reaggregation of the polypeptides that enter the resolving gel. None of the polpeptides observed in the isolated PHF comigrate in the SDS-PAGE with any of the neurofilament polypeptides, tubulin, actin, or myosin.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 54 (1981), S. 63-74 
    ISSN: 1432-0533
    Keywords: Scrapie ; Fibrils ; Amyloid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Abnormal fibrillary structures, designated “scrapie-associated fibrils” (SAF), have been observed using negative stain techniques in subfractions of brains from scrapie-affected animals. SAF have been observed in all combinations of strain of scrapie agent and strain or species of host examined, regardless of their histopathology, in particular the presence or absence of amyloid plaques. SAF consist either of two or four filaments. They are morphologically dissimilar to the normal brain fibrils — microtubules, neurofilaments, glial filaments, and F actin. However, SAF do bear a resemblance to amyloid.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 583-586 
    ISSN: 1432-1041
    Keywords: Carvedilol ; Drug interaction ; digitoxin ; phenprocoumon ; pharmacokinetic interaction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The possibility of a pharmacokinetic interaction between carvedilol and digitoxin (Study I) or phenprocoumon (Study II) has been evaluated in groups of 12 healthy volunteers. The bioavailability (Cmax, tmax, AUC) of digitoxin and phenprocoumon were assessed after a single dose, given once alone and once on day 6 of treatment with carvedilol 25 mg o.d. Cmax, tmax, AUC and Ut of carvedilol and desmethylcarvedilol were also investigated after the fifth dose of carvedilol and after the sixth dose given concomitantly with digitoxin or phenprocoumon. In Study I, the 95% confidence intervals of the ratio test versus the reference findings were; digitoxin Cmax 0.80–1.20, tmax 0.56–1.14, AUC 0.97–1.33, and for carvedilol Cmax 0.81–1.22; tmax 0.66–1.23; AUC 0.91–1.17. Formation of the active metabolite desmethylcarvedilol and the urinary recovery of carvedilol and esmethylcarvedilol were not influenced by digitoxin. In Study II Cmax and AUC of phenprocoumon were not changed after carvedilol. Cmax of carvedilol was decreased after phenprocoumon. The kinetic parameters of phenprocoumon were Cmax 0.80–1.05, tmax 0.47–2.00, AUC 0.78–1.05, and for carvedilol Cmax 0.59–1.06, tmax 0.71–1.73; AUC 0.80–1.08, respectively. The plasma levels of desmethylcarvedilol and the urinary recovery of carvedilol and desmethylcarvedilol were not influenced by phenprocoumon. The blood pressure and heart rate after carvedilol alone were not affected by concomitant administration of digitoxin or phenprocoumon.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physica B: Physics of Condensed Matter 180-181 (1992), S. 1035-1038 
    ISSN: 0921-4526
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Applied crystallography online 23 (1990), S. 444-445 
    ISSN: 1600-5767
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Geosciences , Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    The European physical journal 348 (1994), S. 147-150 
    ISSN: 1434-601X
    Keywords: 06.20.Hq ; 42.50.Wm ; 29.20.Dh
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The transition frequencies of thei-component of the R(99)15-1 and thew-component of the R(85)26-0 transition in the B-X system of molecular127I2 have been determined with an overall relative standard uncertainty of 1.3 · 10−10. For this purpose a commercial linear dye laser has been modified and stabilized to the corresponding iodine line. This dye laser serves as a transportable frequency standard which is compared with the wavelength standards of the PTB. The evaluation of an experiment for testing special relativity at the test storage ring (TSR) in Heidelberg is based on the precision of the reported interferometric wavelength comparison.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0649
    Keywords: 03.30.+p ; 29.20Dh ; 42.50.Wm
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Laser spectroscopy at the heavy ion storage ring TSR in Heidelberg allows for precision experiments testing the limits of the special theory of relativity. With an opticalΛ-type three-level system of7Li+ the Doppler shift has been measured by saturation spectroscopy as a test of the time dilatation factor γ = (1 −β 2)−1/2 at an ion velocity ofυ = 6.4% c. A precision ofΔν/ν 〈 9 × 10−9 has been obtained, which sets a second-order limit of 1.1 × 10−6 for any deviation from the time dilatation factor. The fourth-order limit of this deviation is set below 2.7 × 10−4 by the present experiment. These limits are given at a 1 σ confidence level.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1434-601X
    Keywords: 03.30.+p ; 29.20.Dh ; 32.90.+a
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We have performed for the first time precision spectroscopy on a coasting fast7Li+ ion beam in a storage ring. The ion beam moving with 6.4% speed of light was first electron cooled and then merged with two counterpropagating laser beams acting on two different hyperfine transitions sharing a common upper level (λ-system). One laser was frequency locked to thea 3 127J2 hfs frequency component established as a secondary frequency standard at 514 nm. The second laser was tuned over theλ-resonance, which was recorded relative to127J2 hfs components. This experiment is sensitive to the time dilation in fast moving frames and will lead to new limits for the verification of special relatively. The present status of the experiment and perspectives in accuracy are discussed.
    Type of Medium: Electronic Resource
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