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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Anatomy and embryology 165 (1982), S. 315-328 
    ISSN: 1432-0568
    Keywords: Rabbit photoreceptor ; Retina ; Microtubules ; Protofilaments ; Connecting cilium ; Outer doublets ; Microtubule assembly ; Tubulin of oligomers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The connecting cilium of the rabbit photoreceptor rod is composed of nine outer doublets, lacking dynein side arms. The central singlet microtubules are absent. In cross section, there is an inner dense ring situated between the doublets and the center core of the cilium. As the doublet microtubules progress from the connecting region into outer segments, the cylindrical array of the nine pairs of doublets spreads out as a brush-like arrangement into the incisure cavity of the outer segment. The microtubules continue as doublets for much of the length of the outer segment. The B-tubules terminate first; the A-tubules extend as single tubules into the apical region of the photoreceptor. Before the B-tubules end, they open up, forming hook-shaped projections from the A-tubules. The gradual reduction in length of these hook-shaped structures suggests that near their distal ends each B-tubule opens because of the separation of protofilament 1 of the B-tubule from protofilament 1 of the adjacent A-tubule. Subsequently, the B-tubule protofilaments terminate individually.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 53 (1981), S. 107-112 
    ISSN: 1432-0533
    Keywords: Dendrites ; Purkinje cells ; Golgi stain ; Experimental phenylketonuria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparison was made of cerebellar dendritic development in the normal rat and in a new model of phenylketonuria, the phenylacetate-treated suckling rat. Golgi stain analysis of the Purkinje cells shows striking regional variations in the dendritic growth. These variations were observed in both the control and phenylacetate-treated animals and were especially striking before 15 days of life. Quantitative analysis of the dendritic tree revealed, in the phenylacetate-treated rat, a significant reduction in the total number of dendritic branches. However, the individual terminal dendritic length was largely unaltered. These effects of phenylacetate differ from those of deafferentation and starvation. Results of this investigation clearly define the harmful effects of phenylacetate on developing neurons and are compatible with the clinical observation that brain damage in phenylketonuria occurs mainly during the first few years of life, the critical period of neuronal development.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 68 (1985), S. 175-184 
    ISSN: 1432-0533
    Keywords: Aluminum localization ; Nucleolus ; Ribosomal RNA ; DNA ; Astrocytic process
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Aluminum was observed in the nucleolus, interchromatin granules, rough endoplasmic reticulum, free ribosomes, euchromatin, and the heterochromatin of the neuron. The association of aluminum with the first four r-RNA-containing cellular components and with the last two DNA-containing chromatins suggests the association of aluminum with the nucleic acids. The aluminum may interfere with the normal mechanism of the protein synthesis of r-RNA and of the transcription or gene modulation of DNA. Aluminum was also observed in the astrocytic process and in the nuclei of endothelial cells, pericytes, and the muscle cells of the blood vessels. The detection of aluminum in the pyrimidal cells of the cerebral cortex and hippocampus and in the spinal cord neurons, was observed 1 h after i. v. injection, indicating a rapid entry of aluminum from the injection site through the blood-brain barrier (BBB) to the neurons. Using Morin stain, pyramidal neurons of the cerebral cortex and hippocampus, motoneurons of spinal cord, ganglion cells, and bipolar cells of retina and Purkinje cells of cerebellum, exhibited yellow fluoroscence, with peak intensitiy at 560 nm. Tangles were observed in these six types of neurons. The granule cells of hippocampus and cerebellum and the photoreceptors of the retina exhibited green fluorescence with the peak intensity at 490–500 nm. Tangles were not observed in these three types of neurons.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Synaptic density ; Phenylketonuria ; Phenylacetate neurotoxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In experimental phenylketonuria, induced in the rat by exposure to phenylacetate during the first 21 days of life, there was a significant reduction of boutons, a decrease of an average of 25% in the whole cerebellar molecular layer. Both the density of synaptic profiles per square unit and the number of synapses per unit volume were decreased in the phenylacetatetreated rat as compared to the age-matched control. Neuronal density was unaffected. Results are interpreted to show a deficit of synapses per neuron, probably due to a decrease in synaptic formation in phenylacetate-induced phenylketonuria. Undernutrition was eliminated as a contributing factor.
    Type of Medium: Electronic Resource
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  • 5
    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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  • 6
    ISSN: 1432-0533
    Keywords: Neuritic (senile) plaque ; Alzheimer disease ; Down's syndrome ; Aging brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Quantitative studies of neuritic (senile) plaques in six cortical layers were carried out in brains from people with confirmed clinical and neuropathological diagnosis of senile dementia of the Alzheimer type (SDAT) and Down's syndrome (DS). The same studies were performed on brains of normal old-aged people. In Alzheimer disease (AD) and DS cases the highest numbers of neuritic plaques (NP) were observed in temporal lobe layers III and II and occipital lobe layers III, IV and II. In normal old-aged people the highest numbers of NP were found in temporal lobe III and V and in occipital lobe IV, III, and V layer. The plaque numbers in both temporal and occipital cortices of AD and DS were significantly higher than that of normal old-aged people but there was no difference between AD and DS.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Alzheimer's disease ; Amyloidosis ; β-protein ; Immunocytochemistry ; Paired helical filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Immunocytochemical staining with monoclonal antibodies to the β-protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the β-protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word “plaques” does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto-and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0533
    Keywords: Alzheimer disease ; Mental retardation ; Neuritic plaques ; Neurofibrillary tangles ; Paired helical filaments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the brains of 385 mentally retarded adults aged 23–90 years without Down's syndrome (DS), metabolic disorder, or hydrocephalus to extend our knowledge about the occurrence of Alzheimer-type neuropathology in this population. Relevant measures of neuropathology also were related to selected information available from clinical records. The presence of one or more neurofibrillary tangles (NFT) and/or neuritic plaques (NP) was observed in 63.4% of all cases and varied with age. The prevalence of positive cases was higher when mental retardation was due to head trauma, congenital malformation, or familial factors and when a history of seizures was reported. Comprehensive morphometric analyses of neocortical, hippocampal and parahippocampal areas indicated that recommended agespecific quantitative criteria for the diagnosis of Alzheimer disease [Khachaturian ZS (1985) Arch Neurol 42:1097–1105] were met in 9.5% of cases less than 50 years of age, 54.2% between 50 and 65, 70% between 66 and 75, and 87% of the cases greater than 75 years of age. However, a limited immunohistochemical study revealed that in most cases the NP did not have a neuritic component containing paired helical filaments and in this respect most of the plaques observed in this population may differ from those most strongly associated with Alzheimer disease. In addition, substantial numbers of NFT were seen in frontal cortex, contrasting with results reported in the literature for nonretarded populations. The number of NP per mm2 consistently increased with age for all areas examined, while the relationship between NFT density and age varied across areas, and was clearly not monotonic. Our studies show that the neuropathological lesions currently considered hallmarks of Alzheimer disease are prevalent among non-DS mentally retarded adults, and the regional density of these lesions is high. Thus, while people with DS are affected at an earlier age, clear Alzheimer neuropathology develops in many mentally retarded individuals.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 78 (1989), S. 22-27 
    ISSN: 1432-0533
    Keywords: Neuritic plaques ; Alzheimer disease ; Down syndrome ; Normal aging ; Immunostaining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The sensitivities of four staining methods for detecting the presence of neuritic plaques in the normal aging. Alzheimer disease (AD) and Down's syndrome (DS) brains were compared. The Bielschowsky method and immunostaining with monoclonal antibody (4G8, IgG2b) to β-amyloid revealed the highest numbers of plaques. The thioflavin S-staining method showed about 38%–70% of plaques as shown by the Bielschowsky method. The Bodian method is the least sensitive method revealing about 26%–39% of plaques as compared with the Bielschowsky method. In the first part of this study, serial sections (6 μm) of the plaques from AD and DS brains were cut and stained with Bielschowsky, thioflavin S and Bodian methods, respectively. In the second part, Bielschowsky and immunostaining methods were used to stain serial sections (6 μm) of plaques from the same block of brain tissue. A Zeiss Axiophot fluorescence microscope, coupled with the Cambridge Quantiment 970 and Zeiss Videoplan computerized image analyzers, was used to quantify the number of plaques. Both Bielschowsky and immunostaining methods revealed the presence of both the peripheral zone (halo) and the central core of a classical plaque and resulted in the highest plaque counts. The central core of the thioflavin S-stained plaques were still clearly present, but the peripheral zone was barely visible. In Bodian stain, however, both central core and peripheral zone were poorly stained and not detectable by computer. They were quantified by human eye observation. The Bielschowsky method and immunostaining with pretreatment with formic acid are, therefore, the most sensitive methods showing the highest contrast of plaque image and thus facilitate the quantification of plaque by computer. However, Bielschowsky method is not a specific method for plaques. It stains neurofibrillary tangles and blood vessels regardless of whether they have amyloid deposits or not. Immunostaining is a sensitive and specific method for amyloid and exhibits low background staining. It confirmed that all Bielschowsky-stained plaques contained amyloid deposit.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0533
    Keywords: Key words Amyloid β protein ; Skin biopsy ; Alzheimer's disease ; Down's syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A total of 66 skin biopsies from persons with Alzheimer's disease (AD) or Down's syndrome (DS) and from persons without AD were used in this study. The age range was from 7 to 89 years. Positive immunoreactivity of skin biopsies to monoclonal antibody 4G8, which is reactive to amino acid residue 17 – 24 of synthetic amyloid β protein (Aβ), and 4G8-Fab (the antigen-binding fragment of 4G8 IgG, reactive only to amyloid plaque) was observed in the epidermis-dermis junction or the basement membrane of the epidermis and in some blood vessels of the biopsy skins of 13/18 (72  %) AD, 9/10 (90  %) DS, and 14/38 (37  %) non-AD control cases. The Fisher exact probability test revealed a significant difference (P=0.0415 one-tailed) in immunoreactivity between AD and age-matched controls. There was also a significant difference (P=0.0152 one-tailed; P=0.0200 two-tailed) between DS and age-matched control in the same test. Immuno-gold electron microscopy examination of these cases with positive immunoreactivity revealed that the gold particles were deposited along the basement membrane of the epidermis. Amyloid fibrils were not observed in the regions with gold particles. Results of this study suggest that Aβ is associated with the basement membrane of skin and is present in amorphous, non-fibrillar form as soluble Aβ.
    Type of Medium: Electronic Resource
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