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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 107 (2000), S. 1-29 
    ISSN: 1435-1463
    Keywords: Keywords: Parkinson's disease, neurodegeneration, programmed cell death, TUNEL method, apoptosis, apoptosis regulating proteins, stress proteins.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Objective. While the causes of neuronal death in Parkinson's disease (PD) and other neurodegenerative disorders are still unknown, several mechanisms are under discussion: programmed vs. passive cell death (apoptosis vs. necrosis), mainly based on conflicting results on the rare presence or absence of DNA fragmentation in substantia nigra neurons using the in situ DNA-labeling (TUNEL) method. Design/Methods. In 4 cases of Parkinson's disease (PD), 2 cases of Dementia with Lewy bodies (DLB) and 3 age-matched controls, the TUNEL/ISEL method was used to detect DNA fragmentation in substantia nigra locus coeruleus and cerebral cortex [method by Gold et al. (1994)]. In addition, immunohistochemistry was performed for an array of apoptosis-related proteins, i.e. the recently described apoptosis specific protein cJun/AP1 (ASP), the proto-oncogenes c-Jun, c-Jun AP1, Bcl2, Bax, Bcl-x, p53, CD 95 (Fas/Apo-1), activated caspase 3, several heat shock proteins (α-B crystallin, ubiquitin), and α-synuclein. Results. None of the cases of PD, DLB, and controls showed convincing TUNEL-positivity nor morphologic signs of apoptosis in nigral, locus coeruleus or cortical neurons with or without Lewy bodies but variable numbers of TUNEL-positive astrocytes and microglial cells in substantia nigra of PD and DLB. There were no significant differences in the expression of c-Jun, ASP, Bcl-2, Bax, and Bcl-x in substantia nigra neurons between PD, DLB, and controls nor between cortical and subcortical neurons with and without Lewy bodies. No expression of p53, and activated caspase 3, or any of the examined stress proteins was seen in neurons, while reactive astroglia and microglia were decorated by antibodies to Bcl-2, Bax, α-B-crystallin and less, to Bcl-x and caspase 3. Lewy bodies, dystrophic neurites and axonal spheroids, all being negative for the applied apoptosis regulating proteins, showed strong expression of the examined stress proteins and of α-synuclein. Conclusions. These findings which are in line with previous results in Alzheimer's disease (Stadelmann et al., 1998) and Parkinson's disease (Banati et al., 1999) suggest that mechanisms distinct from classical apoptosis play a central role in the pathogenesis of PD and related neurodegenerative diseases. Further studies are warranted to elucidate the intracellular cascade of events leading to cell death in these disorders showing slow progression over many years.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Der Nervenarzt 71 (2000), S. 929-935 
    ISSN: 1433-0407
    Keywords: Schlüsselwörter Demenz mit Lewy-Körperchen ; Demenz vom Alzheimer-Typ ; Parkinson-Krankheit ; L-Dopa ; Neuroleptika ; Azetylcholinesterase-Hemmer ; Keywords Dementia with Lewy bodies ; Dementia of the Alzheimer type ; Parkinson's disease ; L-Dopa ; Acetylcholine esterase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, parkinsonian syndrome, fluctuations of cognitive functions, alertness, and attention, visual hallucinations (usually detailed and well described), depression, REM sleep behavior disorder, adverse responses to standard neuroleptics doses, falls, syncopes, systematized delusions, and other modalities of hallucinations. Specificity of the clinical diagnostic criteria is high (95%), and sensitivity is considerably lower. Mean age at disease onset ranges between 60 and 68 years. The male gender prevails. Disease duration is 6 to 8 years. The differential diagnoses of DLB are dementia of the Alzheimer type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and rarely Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. Controlled pharmacological studies have so far not been published. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha receptor-blocking medications to improve neurogenic bladder dysfunction.
    Notes: Zusammenfassung Die Demenz mit Lewy-Körperchen (DLK) ist die zweithäufigste neuropathologisch diagnostizierte degenerative dementielle Erkrankung. Ihre klinischen Charakteristika sind progrediente Demenz, Parkinson-Symptome, Schwankungen der Hirnleistungen und Vigilanz, detaillierte wiedergegebene visuelle Halluzinationen, Depression, REM-Schlaf-Verhaltensstörungen, Überempfindlichkeit auf die Dosen üblicher Neuroleptika, Stürze, Synkopen, systemisierter Wahn und Halluzinationen anderer Art. Die klinischen Kriterien haben eine hohe Spezifität (95%) und eine deutlich geringere Sensitivität. Die Erkrankung beginnt im Schnitt zwischen dem 60. und 68. Lebensjahr, betrifft Männer häufiger als Frauen und dauert 6–8 Jahre. Differenzialdiagnosen sind Demenz vom Alzheimer-Typ (DAT), Parkinson-Krankheit (PK), subkortikale arteriosklerotische Enzephalopathie, progressive supranukleäre Parese, Multisystematrophie und bisweilen die Creutzfeldt-Jakob-Erkrankung. Der genetische Hintergrund der Erkrankung ist ungeklärt. Bildgebende Diagnostik (Magnetresonanz-Imaging, Single-Photon-Emission-Tomographie) kann zur Differenzialdiagnose beitragen. Systematische Therapiestudien liegen noch nicht vor. Die Erkrankung wird mit L-Dopa, atypischen Neuroleptika, Azetylcholinesterase-Hemmern, blutdrucksteigernden Medikamenten, sowie zur Verbesserung der neurogenen Blasenstörungen mit peripheren Anticholinergika und α-Rezeptorenblockern behandelt.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 99 (2000), S. 583-584 
    ISSN: 1432-0533
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Key words Human brain ; Hippocampus ; Alzheimer’s disease ; Chromogranin B ; Synapse loss
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Synapse loss is crucially involved in cognitive decline in Alzheimer’s disease (AD). This study was performed to investigate the distribution and density of chromogranin B-like immunoreactivity in the hippocampus of control compared to AD brain. Chromogranin B is a large precursor molecule found in large dense-core vesicles. For immunocytochemistry we used an antiserum raised against a synthetic peptide (PE-11) present in the chromogranin B molecule. Chromogranin B-like immunoreactivity was concentrated in the terminal field of mossy fibers, the inner molecular layer of the dentate gyrus and in layer II of the entorhinal cortex. In AD, chromogranin B was detected in neuritic plaques. The density of chromogranin B-like immunoreactivity was significantly reduced in the inner molecular layer of the dentate gyrus and in layers II, III and V of the entorhinal cortex in AD brains. The present study demonstrates that chromogranin B is a marker for human hippocampal pathways. It is particularly suitable for studying nerve fibers terminating at the inner molecular layer of the dentate gyrus. It is present in neuritic plaques, and its density is reduced in a layer-specific manner.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Key words AIDS ; Extracerebral pathology ; Central nervous system lesions ; Opportunistic infections
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A retrospective study of 450 consecutive AIDS autopsy cases (397 males, 53 females; mean age at death 38.4 years) in Vienna, Austria, between 1984 and 1999 compares the central nervous system (CNS) findings in three cohorts: 1984–1992 (190 cases), 1993–1995 (162 cases) and 1996–1999 (98 cases, after introduction of triple antiretroviral therapy) and the relationship of CNS findings to systemic AIDS pathology in the latter two cohorts. In these two groups, following involvement of the lung (85% and 75%, respectively), the brain continued to be the second most frequently involved organ (decrease from 80% to 60%, respectively). Extracerebral protozoal (Pneumocystis carinii, toxoplasmosis), Mycobacterium avium complex, viral [e.g., cytomegalovirus (CMV)], multiple opportunistic organ and CNS infections, and Kaposi sarcoma significantly decreased over time. There was less decrease in fungal infections, while bacterial organ and CNS infections (except for mycobacteriosis), lymphomas, HIV-associated CNS lesions (around 30%), non HIV-associated changes (vascular, metabolic, etc.) and negative CNS findings (10–11%) remained unchanged. Nonspecific CNS changes (e.g., meningeal fibrosis) increased. Extracerebral pathology in subjects with advanced HIV-related CNS lesions showed more frequent but decreasing systemic bacterial and CMV infections than those with negative or nonspecific neuropathology, while other opportunistic and multiple organ infections and lymphomas showed no differences between both groups. In a cohort of drug abusers, HIV encephalitis, progressive multifocal leukoencephalopathy, bacterial infections, hepatic encephalopathy, and negative CNS findings were more frequent than in non-users who showed increased incidence of CMV, toxoplasmosis, or other opportunistic CNS infections, and nonspecific CNS findings; the frequency of lymphomas was similar in both drug abusers and non-users. Similar to a recent autopsy study from San Diego, these data suggest that despite the beneficial effects of modern antiretroviral combination therapy, involvement of the brain in AIDS subjects continues to be a frequent autopsy finding, while the increased incidence of HIV encephalitis in our small cohort of drug users was less than observed in other recent autopsy studies.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Der Internist 41 (2000), S. 524-537 
    ISSN: 1432-1289
    Keywords: Schlüsselwörter Demenz ; Alzheimer-Krankheit ; Neuropathologie ; genetische Marker ; Liquorparameter
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zum Thema Die Zunahme dementieller Erkrankungen und ihre Diagnose sind ein vordringliches Problem der modernen Altersmedizin. Die klinisch-diagnostischen Trefferquoten liegen bei Anwendung etablierter Konsenskriterien und Zusatzbefunde für die Alzheimer-Krankheit als häufigste Demenzursache bei rund 90%, für andere degenerative Demenzen weit niedriger. Der aktuelle Stand der Neuropathologie der wichtigsten degenerativen Demenzen, Alzheimer-Krankheit, Demenz mit Lewy-Körpern, frontotemporale Demenzen und andere Tauopathien (Progressive supranukleäre Lähmung, Kortikobasale Degeneration) und Chorea Huntington wurden in diesem Beitrag vorgestellt. Auch die wichtigsten genetischen Marker wie das ApoE-ɛ4-Allel sowie andere biologische Marker und ihr aktueller diagnostischer Aussagewert wurden diskutiert. Dabei sind Kombinationen von Markern bei der Diagnosestellung erfolgversprechender als einzelne Parameter.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neurology 247 (2000), S. 309-310 
    ISSN: 1432-1459
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1435-1463
    Keywords: Keywords: Alzheimer disease ; dementia ; nicotinamide adenosine dinucleotide ; blood brain barrier ; open clinical trial.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Reduced nicotinamide adenine dinucleotide (NADH) is advertised as an over-the-counter product or dietary supplement to treat Alzheimer's disease. We performed a 3-month open-label study with oral 10 mg/day NADH with 25 patients with mild to moderate dementia of the Alzheimer, vascular, and fronto-temporal types in addition to their current cholinomimetic drug medication. In 19 patients who completed the study, we found no evidence for any cognitive effect as defined by established psy-chometric tests. We conclude that NADH is unlikely to achieve cognitive improvements in an extent reported earlier, and present theoretical arguments against an effectiveness of this compound in dementia disorders.
    Type of Medium: Electronic Resource
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