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  • 1
    ISSN: 1432-0533
    Keywords: Key words Alzheimer’s disease ; Substantia nigra ; Striatum ; Parkinson’s disease ; Neurofibrillary tangles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although Alzheimer’s disease may involve both the substantia nigra and the striatum, there is little information concerning the relationship between the resulting abnormalities in these reciprocally interconnected regions of the brain. We have examined the correlation between plaque density in the striatum and counts of neurons and neurofibrillary tangles in the pars compacta of the substantia nigra, in 12 cases of “pure” Alzheimer’s disease (i.e. without clinical or neuropathological evidence of Parkinson’s or cortical Lewy body disease) and 11 normal controls. Diffuse plaques in the striatum and neurofibrillary tangles in the substantia nigra were consistent findings in all of the Alzheimer brains. However, quantitation did not reveal a statistically significant correlation between the density of striatal plaques and the numbers of either neurofibrillary tangles or neurons in the substantia nigra. Although the mean number of neurons in the substantia nigra of Alzheimer brains was lower than that in controls, the difference did not reach statistical significance. We suggest that previous assessments of substantial loss of nigral neurons in Alzheimer’s disease may have been skewed by the inclusion of cases with coexistent cortical Lewy bodies.
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  • 2
    ISSN: 1432-0533
    Keywords: Key words Neurofibrillary tangles ; Microtubule-associated protein tau ; Heparan sulphate ; α-Synuclein ; Neurodegenerative diseases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Microtubule-associated protein tau forms neurofibrillary lesions in Alzheimer’s disease and several other neurodegenerative disorders, such as Niemann-Pick disease type C, subacute sclerosing panencephalitis, argyrophilic grain disease, myotonic dystrophy and motor neuron disease with neurofibrillary tangles. In this study we have compared the characteristics of tau pathology in these diseases using immunohistochemistry and phosphorylation-dependent and phosphorylation-independent anti-tau antibodies. The pattern of staining for heparan sulphate and α-synuclein was also investigated. We show that in all of these diseases tau deposits were stained by all anti-tau antibodies used, with the exception of argyrophilic grains which do not stain with antibody 12E8, confirming our previous findings. Heparan sulphate staining was present to a variable extent in all of these diseases, with the exception of subacute sclerosing panencephalitis, in which no staining was observed. Heparan sulphate staining coexisted with tau staining. In some cases it was more extensive than the tau staining. α-Synuclein staining was present in presynaptic terminals with the exception of one case of Alzheimer’s disease, in which α-synuclein-positive Lewy bodies were observed in the hippocampal formation. These findings indicate that tau deposits are antigenically similar in several neurodegenerative diseases and that tau staining is often associated with heparan sulphate staining, supporting the concept that heparan sulphate may be involved in the assembly of tau protein into filaments.
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  • 3
    ISSN: 1432-0533
    Keywords: Venom ; Sodium channel ; Node of Ranvier ; Myelinated nerve fibre ; Myelin sheath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The venoms of the spiderPhoneutria nigriventer and the scorpionsLeiurus quinquestriatus andCentruroides sculpturatus cause acute, transient swelling of axons at nodes of Ranvier. The changes in the morphology of the node and paranode were studied in the mouse. Venom was injected into the sciatic nerve by means of a glass micropipette. After survival times ranging from 15 min to 3 weeks the nerves were examined by light and electron microscopy. The increase in nodal axoplasmic volume led within an hour to disruption of neurofilaments and microtubules, swelling of the paranodes and displacement of the terminal loops of myelin away from the node. Axonal calibre recovered within a few hours, but restoration of nodal width took several days and seemed to be accomplished by elongation and remodelling of the paranodal myelin. Occasional internodes were interrupted by node-like discontinuities in the myelin sheath. These developed within a few hours and persisted for the duration of the study.
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  • 4
    ISSN: 1432-0533
    Keywords: Key words Spinal cord injury ; Stroke ; B7 molecules ; Macrophage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lesion-induced microglial/macrophage responses were investigated in post-mortem human spinal cord tissue of 20 patients who had died at a range of survival times after spinal trauma or brain infarction. Caudal to the spinal cord injury or brain infarction, a strong increase in the number of activated microglial cells was observed within the denervated intermediate grey matter and ventral horn of patients who died shortly after the insult (4–14 days). These cells were positive for the leucocyte common antigen (LCA) and for the major histocompatibility complex class II antigen (MHC II), with only a small proportion staining for the CD68 antigen. After longer survival times (1–4 months), MHC II-immunoreactivity (MHC II-IR) was clearly reduced in the grey matter but abundant in the white matter, specifically within the degenerating corticospinal tract, co-localising with CD68. In this fibre tract, elevated MHC II-IR and CD68-IR were still detectable 1 year after trauma or stroke. It is likely that the subsequent expression of CD68 on MHC II-positive microglia reflects the conversion to a macrophage phenotype, when cells are phagocytosing degenerating presynaptic terminals in grey matter target regions at early survival times and removing axonal and myelin debris in descending tracts at later survival times. No T or B cell invasion or involvement of co-stimulatory B7 molecules (CD80 and CD86) was observed. It is possible that the up-regulation of MHC II on microglia that lack the expression of B7 molecules may be responsible for the prevention of a T cell response, thus protecting the spinal cord from secondary tissue damage.
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  • 5
    ISSN: 1432-0533
    Keywords: Encephalomyeloneuropathy ; Sensory neuropathy ; Brain stem encephalitis ; Limbic encephalitis ; Ganglioradiculitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical and postmortem findings in three cases of encephalomyeloneuropathy are reported. Two patients presented with subacute sensory neuropathy and one with amnesia and confusion. In none of these cases was a tumour detected clinically or at autopsy. Neuropathological examination showed inflammatory lesions in the brain, spinal cord and posterior root ganglia indistinguishable from encephalomyeloneuropathy occurring as a remote effect of carcinoma.
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  • 6
    ISSN: 1432-0533
    Keywords: Amyotrophic lateral sclerosis ; Neurofilaments ; Spinal muscular atrophy ; Neuromuscular diseases ; Motor neurons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A caucasian male with a history of mental retardation and intractable epilepsy since birth, developed progressive wasting and weakness of skeletal muscles, leading to death at 4 years of age. A biopsy of gastrocnemius muscle at 2 years of age revealed severe neurogenic atrophy. Sural nerve biopsies at 2 and 3 years showed progressive atrophy and loss of large myelinated nerve fibers with a paucity of neurofilaments in remaining nerve fibers. Postmortem immunohistochemical and ultrastructural examination showed that neurons were markedly distended by phosphorylated neurofilaments. Whereas large lower motor neurons were most severely involved, dorsal root ganglia and neurons in the cerebral cortex and deep gray nuclei were also affected. It is suggested that this disease is caused by a disorder of neurofilament phosphorylation and transport.
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  • 7
    ISSN: 1432-0584
    Keywords: Acute myeloid leukemia ; Cytosine arabinoside ; Elderly ; Mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (〉 59 years) referred over a 3.5-year period, 33 patients (age range 60–78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1–37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/ Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.
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  • 8
    ISSN: 1432-0584
    Keywords: Key words Acute myeloid leukemia ; Cytosine arabinoside ; Elderly ; Mitoxantrone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (〉59 years) referred over a 3.5-year period, 33 patients (age range 60–78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1–37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/ Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 9 (1954), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1434-6052
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract We list all dimension sixSU(3)×SU(2)×U(1) invariant operators which can be used in a phenomenological analysis of deviations from the standard model due to a new interaction scale. Specific attention is focused on modifications to the masses of theW andZ bosons.
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