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  • 1
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    ISSN: 0044-8249
    Keywords: Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The Human Combinatorial Antibody Library (HuCAL) was screened for antibodies specific to human leukocyte antigen-DR (HLA-DR) that induce programmed death of lymphoma/leukemia cells expressing the target antigen. The active Fab fragments were affinity-matured, and engineered to IgG4 antibodies of ...
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  • 3
    ISSN: 1072-8368
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The catalytic activity of Src family tyrosine kinases is inhibited by intramolecular interactions between the regulatory SH3 and SH2 domains and the catalytic domain. In the inactive state, the critical αC-helix in the catalytic domain is positioned such that the formation of the Glu ...
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  • 4
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Neurodegeneration ; Demenz ; Tau ; Synuclein ; Hirngewebebank ; Keywords Neurodegeneration ; Dementia ; Tau ; Synuclein ; Brain bank
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Neurodegenerative and dementing disorders such as Parkinson disease and Alzheimer disease are among the most common diseases of advanced age. Despite progress in the clinical diagnosis of neurodegenerative disorders, definite diagnosis for most of these disorders is still possible only by neuropathological examination of the brain. The neuropathological diagnosis and classification of neurodegenerative disorders has made clear advances in recent years, particularly due to the results of genetic and biochemical studies, resulting in the development of new disease-specific antibodies. Internationally recognized consensus criteria for most neurodegenerative disorders allow a definite and standardized diagnosis to be made. To obtain further knowledge about the etiopathogenesis, particularly with regard to new therapeutic strategies, studies with clinically and neuropathologically well-documented cases are needed. The project “Brain-Net” has therefore been established with the aim of setting up a German Brain and Tissue Bank for Diseases of the Central Nervous System. The project is funded by the Federal Ministry of Education and Research.
    Notes: Zusammenfassung Neurodegenerative und demenzielle Erkrankungen wie Morbus Parkinson und Morbus Alzheimer zählen zu den häufigsten Erkrankungen im höheren Lebensalter. Trotz Fortschritte in der klinischen Diagnostik ist eine sichere Diagnosestellung derzeit nur durch eine neuropathologische Untersuchung des Gehirns möglich. Die neuropathologische Diagnostik und Einteilung der neurodegenerativen Erkrankungen hat dabei in den letzten Jahren deutliche Fortschritte gemacht. Zum Großteil ist dies neuen Erkenntnissen aus genetischen und biochemischen Studien zu verdanken, die die Entwicklung neuer krankheitsspezifischer Antikörper ermöglicht haben. Für zahlreiche neurodegenerative Erkrankungen stehen nun international verwendete Diagnosekriterien zur Verfügung, die eine sichere und standardisierte Diagnostik erlauben. Für weitere Fortschritte in der Erforschung der Ätiopathogenese und der Therapie neurodegenerativer Erkrankungen sind weitere Untersuchungen an Hirngewebe von klinisch und neuropathologisch gut dokumentierten Fällen nötig. Um dies zu gewährleisten, wurde das vom Bundesministerium für Bildung und Forschung geförderte Projekt “Brain-Net” ins Leben gerufen mit dem Ziel, eine Deutsche Hirngewebebank aufzubauen.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Key words NBIA type 1 ; Hallervorden-Spatz ; syndrome ; α-synuclein ; Lewy body
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied a 27-year-old woman who died after a 6-year history of progressive dementia, dystonia, ataxia, apraxia, spasticity, choreoathetosis, visual and auditory hallucinations, and optic atrophy. Magnetic resonance imaging showed decreased intensity in the globus pallidus, substantia nigra, and dentate nuclei in T2-weighted images, supporting the clinical diagnosis of neurodegeneration with brain iron accumulation type 1 (NBIA-1; formerly known as Hallervorden-Spatz syndrome). At autopsy the brain showed mild frontotemporal atrophy and discoloration of the globus pallidus and the substantia nigra pars reticularis. Histologically, features typical of NBIA-1 were found including widespread axonal spheroids and large deposits of iron pigment in the discolored regions. Additionally, excessive numbers of Lewy bodies (LBs) were found throughout all examined brain stem and cortical regions. LBs of both types, as well as Lewy neurites in this case of NBIA-1, were strongly labeled by antibodies against α-synuclein. These findings give further evidence that accumulation of α-synuclein is generally associated with LB formation, i.e., in Parkinson’s disease, dementia with Lewy bodies and NBIA-1. The case presented here is particularly notable for its high number of LBs in all areas of the cerebral cortex.
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies. Here we analysed in detail the effect of recombinant PrPC and N- and C-terminal fragments of PrPC on the whole-cell current amplitude through voltage-gated calcium channels (VGCCs) of cultured wild-type cerebellar granule cells. With the application of full-length recombinant PrPC (50–500 nm), a highly significant reduction of the whole-cell current amplitude was observed in a dose-dependent manner. Amplitude reduction was abolished when cells were pre-incubated with nifedipine, a specific blocker of voltage-gated L-type calcium channels. N-terminal PrP fragments also led to a dose-dependent reduction of the maximal current amplitude, whereas a C-terminal fragment did not affect the current amplitude. These data demonstrate that nanomolar concentrations of PrPC modulate L-type VGCCs in mouse cerebellar granule cells, an effect that is dependent upon the copper-binding amino-terminal domain of PrPC.
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Previous studies have indicated that recombinant cellular prion protein (PrPC), as well as a synthetic peptide of PrPC, affects intracellular calcium homeostasis. To analyze whether calcium homeostasis in neurons is also affected by a loss of PrPC, we performed microfluorometric calcium measurements on cultured cerebellar granule cells derived from prion protein-deficient (Prnp0/0) mice. The resting concentration of intracellular free calcium ([Ca2+]i) was found to be slightly, but significantly, reduced in Prnp0/0 mouse granule cell neurites. Moreover, we observed a highly significant reduction in the [Ca2+]i increase after high potassium depolarization. Pharmacological studies further revealed that the L-type specific blocker nifedipine, which reduces the depolarization-induced [Ca2+]i increase by 66% in wild-type granule cell somas, has no effect on [Ca2+]i in Prnp0/0 mouse granule cells. Patch-clamp measurements, however, did not reveal a reduced calcium influx through voltage-gated calcium channels in Prnp0/0 mice. These data clearly indicate that loss of PrPC alters the intracellular calcium homeostasis of cultured cerebellar granule cells. There is no evidence, though, that this change is due to a direct alteration of voltage-gated calcium channels.
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  • 9
    Electronic Resource
    Electronic Resource
    350 Main Street , Malden , MA 02148-5018 , USA , and 9600 Garsington Road , Oxford OX4 2DQ , UK . : Blackwell Futura Publishing, Inc.
    ISSN: 1540-8159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: External electrocardiographic loop recording permits extended cardiac rhythm monitoring and ECG storage before and after device activation. The purpose of the study was to assess the diagnostic yield of external loop recorders in patients with more than two syncopal events within the last 6 months and a negative tilt table test. Twenty-four consecutive patients (51 ± 14 years, male n = 9) were enrolled with 3 ± 4 recurrent syncopal events within the last 6 months and no overt structural heart disease. The loop recorder CardioCall continuously records a two-channel ECG via skin electrodes. When activated, up to 4.5 minutes of the ECG preceding activation is stored. The time between tilt table testing and monitoring was 5 ± 4 weeks. The average monitoring period covered 50 ± 22 days. Recording was either unsuccessful or terminated prematurely in 5 patients. The reasons were skin irritation secondary to the electrodes in two patients, cable damage in one patient, and two patients inadvertently erased the stored data when replacing the batteries. Fourteen patients activated the loop recorder at least once. Symptoms leading to device activation were syncope (n = 1), dizziness (n = 11), feeling unwell (n = 7), palpitations (n = 5), headaches (n = 1), and chest pain (n = 1). The loop recorder documented sinus tachycardia during the syncopal event. Sinus tachycardia was also observed in 7 other patients, and atrial flutter in two patients. Eight patients had recurrent syncope with two patients experiencing syncope prior to the monitoring period, one syncope occurred in a patient who inadvertently erased the stored data, one event coincided with sinus tachycardia, and 4 (17%) patients had syncope during 15 ± 10 months after termination of loop monitoring. The external loop recorder was not very useful for arrhythmia detection in patients with syncopal events, no overt heart disease, and a negative tilt table test because the cardiac rhythm was stored in only 1 of 8 (13%) patients with recurrent syncope. Reasons for the low diagnostic yield of external loop recorders were infrequent syncopal events after the baseline evaluation, with rare events during the limited monitoring period in particular, and premature termination or unsuccessful recording in 21% of patients. (PACE 2003; 26:1837–1840)
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