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  • 1
    Electronic Resource
    Electronic Resource
    Detection of cerebrospinal fluid leakage by isoelectric focusing on polyacrylamide gels with silver staining using the PhastSystem™ (1995)
    Springer
    Acta neurochirurgica 136 (1995), S. 135-139 
    Details
    ISSN: 0942-0940
    Keywords: Cerebrospinal fluid (CSF) ; iso-electric focusing (IEF) ; liquorrhea ; tau protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebrospinal fluid (CSF) leakage, which sometimes occurs after skull trauma, is a life-threatening condition. A prompt start with antibiotics and/or prompt surgical treatment of fistulas is essential to avoid severe complications. This requires a fast and reliable method for detecting CSF leakage. This paper describes a fast (〈2 h) method based on the identification of the tau protein (β2-transferrin) band(s). Tau protein is a brain-specific variant of transferrin that is characteristic of CSF. The method includes iso-electric focusing (IEF) on pre-cast polyacrylamide gels and silver staining using the PhastSystem™, an automated instrument for electrophoresis and staining. In the present study, this technology was applied on 200 consecutive CSF samples, 32 of which were from healthy volunteers. Tau protein was detected in all CSF samples but 5 (2.5%), all of which were from patients with blood-brain barrier (BBB) damage. In these cases, the tau protein band was indistinct when direct silver staining was used. Therefore, immunofixation with an antitransferrin antibody was performed, and after that the tau protein band was easy to detect. The specificity of the method was high, since no brain-specific tau protein band was detected in serum, tears, saliva, or nasal secretion. As IEF of CSF using the PhastSystem™ is increasingly used as the routine method for detection of oligoclonal bands of IgG in neurological disorders, it could readily be used in the clinical (neuro) chemical laboratory also for the less frequent cases of suspected CSF leakage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01410615
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  • 2
    Electronic Resource
    Electronic Resource
    Lipid analyses of human brain rafts (2003)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Few studies of lipid rafts have investigated gangliosides in brain tissue. This study focus on analyses of lipids and the major brain gangliosides (GM1, GD1a, GD1b, GT1b) in human cortex (frontal, temporal) and corresponding detergent resistant membranes (DRMs), i.e. rafts. A high proportion of the gangliosides (18–26%) as well as of cholesterol (21%) and sphingomyelin (38%) was found in rafts, while lower yields was observed for ganglioside GM2 (9%), phospholipids (8%) and in particular proteins (2%). Significant alterations in lipid composition was noticed in rafts from Alzheimer brain tissue. These results show that sphingolipids and cholesterol are major constituents of rafts also in the human brain and that the main brain gangliosides are distributed in rafts to a similar degree. Moreover, lipid rafts might be considered in the pathology of Alzheimer's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.85.s2.22_1.x
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  • 3
    Electronic Resource
    Electronic Resource
    Cold-induced photoinhibition and growth of seedling snow gum (Eucalyptus pauciflora) under differing temperature and radiation regimes in fragmented forests (1998)
    Oxford, UK : Blackwell Publishing Ltd
    Plant, cell & environment 21 (1998), S. 0 
    Details
    ISSN: 1365-3040
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Fluorescence characteristics and growth of seedling snow gum (Eucalyptus pauciflora Sieb. ex Spreng.) during autumn and winter were related to variation in radiation and temperature regime in a fragmented forest. Seedlings were planted in four treatments along transects perpendicular to tree island edges to characterize plant responses to microclimates ranging from those of cleared areas to those beneath forest canopies. Three-dimensional mapping of seedling leaf display, in combination with information retrieved from hemispherical photographs about shading from overstory canopies, were used to calculate the intercepted amounts of direct radiation energy for unit area of leaves on clear days (IDRE). IDRE was highest on the outside, most variable at the edges and lowest well inside the tree islands. Minimum temperature decreased with increasing view of the sky. Photoinhibition, measured as decrease in Fv/Fm, was correlated with spatial and seasonal differences in weekly minimum temperature and IDRE. Seedlings in the open and under the most canopy cover, with low variability in IDRE in a scale of weeks, exhibited less variability in photoinhibition than those growing along forest edges. Seedlings in the open tended to be most photoinhibited and grew the most. The combination of increased IDRE with reduced minimum temperatures resulted in persistent and strong photoinhibition as the season progressed. Results are discussed in relation to the potential for seedling establishment following forest fragmentation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3040.1998.00291.x
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  • 4
    Electronic Resource
    Electronic Resource
    Growth-associated protein GAP-43 in the frontal cortex and in the hippocampus in Alzheimer's disease: an immunohistochemical and quantitative study (2000)
    Springer
    Journal of neural transmission 107 (2000), S. 463-478 
    Details
    ISSN: 1435-1463
    Keywords: Keywords: Dementia, neuromodulin, rab3a, senile plaques, synapse, APOE, Western blotting.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. We studied the growth-associated protein, GAP-43 (also called neuromodulin and B-50) in post-mortem brain tissue using immunohistochemistry and quantitative Western blotting, from patients with Alzheimer's disease (AD) and age-matched control subjects. By immunohistochemistry, we found a clear reduction of GAP-43 in the frontal cortex, while in the hippocampus, there was a marked reduction in some areas (dentate molecular layer, stratum moleculare and radiale of CA1 and CA4), while not in other areas (stratum lacunosum, pyramidale and oriens of CA1). Moreover, in the hippocampus, neuritic staining was prominent, and was often associated with senile plaques. Quantitative analysis showed that GAP-43 was significantly reduced in AD, both in the frontal cortex (70% of the control value, p 〈 0.01) and in the hippocampus (81% of the control value, p 〈 0.05). In the frontal cortex, there was a significant negative correlation between GAP-43 and duration of dementia (r = −0.58; p 〈 0.02) and a positive correlation between GAP-43 and the synaptic vesicle-specific protein rab3a (r = 0.62; p 〈 0.05), while no such correlation were found in the hippocampus. In contrast, a significant positive correlation was found between GAP-43 and the number of senile plaques in the hippocampus (r = 0.64; p 〈 0.05), but not in the frontal cortex. GAP-43 is known to be involved in maintenance of synapses and in neuritic regeneration. Our findings may suggest that in the frontal cortex, GAP-43 levels decline as a consequence of the synaptic degeneration, while in the hippocampus, sprouting processes, involving GAP-43, are active.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007020070088
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  • 5
    Electronic Resource
    Electronic Resource
    CSF levels of tau, β-amyloid1–42 and GAP-43 in frontotemporal dementia, other types of dementia and normal aging (2000)
    Springer
    Journal of neural transmission 107 (2000), S. 563-579 
    Details
    ISSN: 1435-1463
    Keywords: Keywords: Alzheimer's disease, frontotemporal dementia, vascular dementia, subcortical, white matter, Parkinson's disease, cerebrospinal fluid, GAP-43, tau, β-amyloid, biochemical marker.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Cerebrospinal fluid (CSF) levels of tau, β-amyloid1–42 and growth-associated protein 43 (GAP-43) were studied in patients with frontotemporal dementia (FTD; n = 17), Alzheimer's disease (AD; n = 60), subcortical white-matter dementia (SWD; n = 24), Parkinson's disease (PD; n = 23) and dysthymia (n = 19) and in age-matched controls (n = 32). CSF-tau was significantly increased only in AD, and CSF-β-amyloid1–42 was significantly decreased in AD and SWD as compared to controls, and in AD compared to FTD. CSF-GAP-43 was significantly decreased only in PD. The GAP-43/tau ratio was decreased in all the patient groups except the dysthymia group compared to controls. A positive correlation was found between CSF-GAP-43 and CSF-tau in all groups. The results suggest normal levels of CSF-tau and CSF-β-amyloid1–42 in FTD, which will aid in the clinical separation of FTD from AD. In SWD, decreased levels of CSF-β-amyloid1–42 suggest concomitant involvement of vascular and amyloid protein mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007020070079
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  • 6
    Electronic Resource
    Electronic Resource
    Reduction of the synaptic protein rab3a in the thalamus and connecting brain regions in post-mortem schizophrenic brains (2000)
    Springer
    Journal of neural transmission 107 (2000), S. 1085-1097 
    Details
    ISSN: 1435-1463
    Keywords: Keywords: Limbic system ; rab3a ; schizophrenia ; synapse ; synaptic ; thalamus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Although the psychotic symptoms in schizophrenia can be alleviated by treatment with dopaminergic receptor antagonists, the etiology and underlying neurochemical pathology remains obscure. Both neuropathological and magnetic resonance imaging studies have found evidence for neuronal loss and atrophy in the thalamus in schizophrenia, implicating this key structure for gating information to cortical areas in the pathophysiology. Recent studies have also found evidence of synaptic loss in the thalamus in schizophrenia. To further examine possible synaptic disturbances, we studied the synaptic related protein rab3a as a marker for synaptic density, using both quantitative Western blotting and immunohistochemistry. The material consisted of brains from 22 schizophrenic patients (mean age 79.3 years), and 24 control subjects (74.8 years). Reduced rab3a protein levels were found in the left thalamus in schizophrenia (0.47 ± 0.17 vs. 1.00 ± 0.18; p 〈 0.0001), while a less marked decrease was found also in the right thalamus (0.75 ± 0.13 vs. 1.00 ± 0.09; p 〈 0.0001). Immunohistochemistry, performed on two schizophrenic and two control brains, revealed that rab3a immunoreactivity was most reduced in the left anterior and mediodorsal thalamic nuclei. Therefore, we extended the study to brain regions connected these thalamic nuclei. Reduced rab3a protein levels were found schizophrenia also in the frontal cortex, hippocampus, gyrus cinguli, and parietal cortex, while no significant differences were found in the temporal cortex, or in cerebellum. The reduction in rab3a was not found to be secondary to confounding factors such as age-differences, post-mortem delay time, generalized brain atrophy, or antipsychotic medication. Therefore, the reduction of rab3a probably reflects synaptic disturbances, possibly synaptic loss, in the limbic system and neocortical areas, in schizophrenia. This part of the brain is known to be in-volved in behavioral and emotional control, and thus to be crucial for higher mental functions, suggesting that synaptic disturbances in the limbic system may be of importance in the development of psychotic symptoms in schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007020070054
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  • 7
    Electronic Resource
    Electronic Resource
    Brain monoaminergic and neuropeptidergic variations in human aging (1996)
    Springer
    Journal of neural transmission 103 (1996), S. 101-115 
    Details
    ISSN: 1435-1463
    Keywords: Human brain ; aging ; monoamines ; neuropeptide Y ; somatostatin ; corticotropin-releasing factor ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of age on the monoamines 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA), their metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3,4-dihydr-oxyphenylacetic acid (DOPAC), and the 5-HT precursor 5-hydroxy-L-tryptophan (5-HTP), together with the peptides neuropeptide Y (NPY), somatostatin (SOM), and corticotropin-releasing factor (CRF), was studied in frontal cortex, gyrus cinguli and hypothalamus from 23 healthy control subjects, aged 16–75 years. After correcting for postmortem interval, significant decreases in gyrus cinguli NA, NPY and CRF, and hypothalamic DA, HVA, and 5-HIAA concentrations were obtained with advancing age. The involvement of the monoaminergic system in several functional abnormalities appearing in senescence is suggested. Furthermore, evidence is given of the participation of the peptidergic systems in the aging process.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01292620
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  • 8
    Electronic Resource
    Electronic Resource
    Synaptic pathology in Alzheimer's disease: Relation to severity of dementia, but not to senile plaques, neurofibrillary tangles, or the ApoE4 allele (1996)
    Springer
    Journal of neural transmission 103 (1996), S. 603-618 
    Details
    ISSN: 1435-1463
    Keywords: Alzheimer's disease (AD) ; apolipoprotein E (ApoE) ; dementia ; neurofibrillary tangles ; rab3a ; senile plaques ; synapses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Alzheimer's disease (AD) is characterised by an increased number of senile plaques (SP) and neuroflbrillary tangles (NFT) as compared with that found in non-demented individuals of the same age, and a marked degeneration and loss of synapses. One of the main risk-factors for the disorder is inheritance of the apolipoprotein E4 (ApoE4) allele. To further study the relation between these pathogenetic substrates for AD, we quantified the synaptic vesicle membrane protein rab3a in brain tissue from 19 patients with AD and 9 age-matched control subjects. Rab3a levels were reduced in AD, both in the hippocampus (60% of control level, p 〈 0.0001), and in the frontal cortex (68% of control level, p 〈 0.01), but not in the cerebellum (92% of control level). Within the AD group, lower rab3a levels were found both with increasing duration and severity of dementia. These findings further support that synaptic pathology is closely correlated to the clinical dementia in AD. In contrast, no significant correlations were found between SP counts and duration or severity of dementia, while higher NFT counts in the frontal cortex were found with increasing severity of dementia (r=0.54, p 〈 0.05). There were no significant correlations between the rab3a level and SP or NFT counts, and by immunohistochemistry, reduced rab3a immunostaining was found throughout the neuropil in AD brain, without relation to SP or NFT. These findings suggest that the synaptic pathology in AD is not closely related to the presence of SP and NFT. No significant differences in rab3a levels were found in any brain region between AD patients possessing different numbers of the ApoE4 allele, suggesting that, although ApoE4 is a risk factor for earlier development of AD, the degree of synaptic pathology does not differ between patients with or without the ApoE4 allele.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01273157
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  • 9
    Electronic Resource
    Electronic Resource
    A new procedure for detecting brain-specific proteins in cerebrospinal fluid (1997)
    Springer
    Journal of neural transmission 104 (1997), S. 711-720 
    Details
    ISSN: 1435-1463
    Keywords: Alzheimer's disease (AD) ; amyloid ; cerebrospinal fluid (CSF) ; transthyretin ; brain-specific proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have developed a new procedure, including three affinity chromatography steps, micro-reversed phase high pressure liquid chromatography (mR-HPLC) and Western blotting/mass spectrometric analysis to study central nervous system (CNS) specific proteins in human cerebrospinal fluid (CSF) in order to find biochemical markers for neuronal and synaptic function and pathology in degenerative brain disorders. After the three affinity chromatography steps, intended to remove interfering serum proteins from CSF, mR-HPLC revealed four major peaks, which by both Western blotting and mass spectrometric analyses were found to correspond to β2-microglobulin, cystatin C, transthyretin (TTR) and asialotransferrin. When comparing these peaks in CSF from Alzheimer's disease (AD) patients and age-matched healthy controls, a reduction of the brain-specific TTR was found. Therefore we quantified TTR in CSF and serum samples from 8 patients with early onset AD (EAD), 18 patients with late onset AD (LAD), 8 patients with vascular dementia (VAD) and 18 healthy individuals using a nephelometric method. CSF-TTR was divided into barrier-dependent and barrier-independent TTR. The barrier-independent i.e. brain-specific TTR was significantly reduced in the EAD group compared to the controls. Transthyretin has been found to be present in the senile plaques in AD, and to specifically bind to β/A4 protein, the major component of the amyloid deposits in AD. Therefore, the reduction of the transthyretin-isoform in CSF in AD may reflect an absorption of transthyretin to the amyloid deposits in the senile plaques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01291888
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  • 10
    Electronic Resource
    Electronic Resource
    No association between the α2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression (2000)
    Springer
    Journal of neural transmission 107 (2000), S. 1065-1079 
    Details
    ISSN: 1435-1463
    Keywords: Keywords: Alzheimer's disease ; apolipoprotein E (apoE) ; senile plaques.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. A polymorphism consisting of a deletion near the 5′ splice site of exon 18 on the α2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p 〈 0.0001) in ApoE ε4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE ε4 allele. No change in A2M exon 17–18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007020070052
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