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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 44 (1985), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: A number of 5-hydroxytryptamine (5-HT) uptake inhibitors have been shown to displace the binding of [3H)imipramine to rat cortical membranes in a complex manner with Hill slopes less than unity. Norzimeldine displaced the binding of [3H]imipramine in a biphasic manner with IC50 values for the two components of about 30 nM and 30 μM. This latter site alone was found in tissues that had been treated with a protease. Binding to both of these sites was displaced by 10μM desipramine. The protease-sensitive [3H]imipramine binding sites were found to be saturable, high-affinity binding sites with a KD of 8 nM. The number of these sites varied between brain regions and was positively correlated with the regional distribution of [14C]5-HT but not [3H]noradrenaline uptake. This was not the case however for the protease resistant but desipramine-displaceable binding sites. Since most previous [3H]imipramine binding studies have been performed with high concentrations of desipramine (10 μ. M) to define “specific binding,” these data would suggest that either protease-sensitivity or displaceability by 1 μM norzimeldine would give more reliable estimates of the specific binding.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 39 (1982), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Human caudate nucleus, putamen, substantia nigra, and nucleus accumbens were analyzed for the effects of age on dopaminergic binding sites. Decreases in the number of dopaminergic binding sites were detected with age in caudate nucleus (44 specimens from three sample groups) and substantia nigra (n = 12). In caudate nucleus, the decline in [3H]2-amino-6,7-dehydroxy-1,2,3,4-tetrahydronaphthalene sites was three times greater than for [3H]spiperone, but age changes were significant in only two of the three sampling groups. No age changes in binding were detected in the putamen (n = 44) or nucleus accumbens. Age, sex, and tissue source all significantly contributed to variance. However, cause of death, time from death to tissue freezing, and length of storage did not influence dopaminergic binding in the caudate nucleus or putamen. Relative to the life-span, the age-correlated decrease in dopaminergic binding sites of human brain approximates that in aging rodent striatum. Comparisons of altered dopaminergic binding with other age-correlated changes suggest that neuronal loss may not be involved in the loss of binding sites before midlife.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 131 (1994), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 22 (1985), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Peripheral blood mononuclear cells from altogether 45 nickel-sensitive patients and 37 controls were assayed for various T and B cell variables. All the patients, but none of the controls, fulfilled our in vitro criteria for a positive response to nickel sulphate (NiSO4). We report normal T and B lymphocyte counts, normal spontaneous plaque-forming cell (PFC) numbers, normal serum immunoglobulin levels, and no demonstrable specific cytotoxic T lymphocyte activity associated with nickel sensitivity. We could detect only a slight increase in the number of PFC and in the number of cytoplasmic immunoglobulin positive (cIg+) cells following stimulation of the patients' cells with NiSO4 for 6 days in culture. A part from a transient increase in the [3H] thymidine uptake by patients' cells stimulated with NiSO4 in vitro, and a transient drop in the OKT4/OKT8 ratio, there were no major differences in the values of the above variables before and after in vivo challenge of 3 patients with NiSO4. Blood from only 2 of the latter 3 patients was tested in the DNA synthesis test. We conclude that apart from the DNA synthesis test, none of these tests is of any use as an aid to diagnosis in patients with nickel sensitivity. A careful attitude towards patch testing should be maintained.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 105 (1998), S. 575-586 
    ISSN: 1435-1463
    Keywords: Keywords: 5-HT4 ; human brain ; BIMU 1 ; BIMU 8 ; ondansetron ; tropisetron.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. In this study, drug inhibition and saturation experiments on the binding of the highly selective 5-HT4 antagonist [3H]GR 113808 were performed in human brain membranes so as to better characterize this binding site. Drug competition studies were carried out by incubating 0.2 nM [3H]GR 113808 in the presence of increasing concentrations of six different drugs, i.e. 5-HT, 5-CT, ondansetron, tropisetron, BIMU 1 and BIMU 8 (mixed 5-HT3 and 5-HT4 agonists). The binding displaced by 5-HT showed a drug inhibition constant (Ki) value of 197 nM. The use of 5-CT or ondansetron also showed the existence of single-site models albeit with Ki values in the micromolar range (11,5 μM). Tropisetron, BIMU 1 and BIMU 8 displaced bound [3H]GR 113808 according to a two-site binding model, with the high affinity component in the nanomolar range and the low affinity site in the micro or mili-molar range. Saturation experiments revealed high binding densities in basal ganglia (187 fmol/mg in putamen, and 149 fmol/mg in caudate nucleus), while lower densities were observed in cortical regions (49 fmol/mg in temporal cortex, 45 fmol/mg in parietal cortex and 71 fmol/mg in cingulate cortex). The apparent affinity (Kd) was similar in the brain regions studied, ranging from 0.13 to 0.34 nmol/l. Despite the enrichment of 5-HT receptors in human brain, their functional correlate in brain diseases remains to be clarified.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-1463
    Keywords: Human brain ; age ; monoamine oxidase ; genetic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of age upon monoamine oxidase -A and -B (MAO-A and -B) in 23 different regions of human brain was determined. There was a significant positive correlation with age in 19 out of 23 regions for MAO-B, but no positive correlation with age was found for MAO-A. The increased MAO-B activity was found, in 5 out of 5 regions tested, to be due entirely to an increased enzyme concentration, rather than due to an increased molecular turnover number of the enzyme. The responses of the mitochondrial marker enzymes succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were studied in 5 brain regions, and no consistent change in activity found with age. The lysosomal enzyme acid phosphatase was found to tend towards an increased activity with age. No difference in either the specific activities or molecular characteristics of MAO were found between men and women. Cross-correlation studies of the data, after compensation for the effects of age, indicated that the activities of the two enzyme forms are under some form of organized control across the whole brain. Such a finding is consistent with a genetic regulation of the enzyme forms.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-1463
    Keywords: Human brain ; cerebral microvessels ; radioligand binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral microvessels were prepared from fresh and frozen human brain samples obtained from autopsy cases. Structural integrity and purity of the microvessels were confirmed by light and electron microscopy, and by measurement of the enzymatic marker γ-glutamyltranspeptidase. Similar morphological and enzymatic characteristics were found for the microvessels prepared from fresh and frozen brain samples. Radioligand binding experiments indicated the presence both in the “fresh” and “frozen” microvessel preparations of specific alpha1-, alpha2-, and beta-adrenergic, histamine H1, serotonin S1 and imipramine binding sites, although the density of beta-adrenergic and histamine h1 specific binding sites were lower in the frozen samples than in the fresh samples. Low levels of specific binding to muscarinic, GABAergic and serotonin S2 sites (with respect to the specific binding densities in the crude homogenates) were found in the microvessel preparations.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 103 (1996), S. 101-115 
    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
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 106 (1999), S. 1141-1149 
    ISSN: 1435-1463
    Keywords: Keywords: GAT-1, GABA transporters, Alzheimer's disease.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The presynaptically located γ-aminobutyric acid (GABA) transporter (GAT-1) was studied in a group of patients with Alzheimer's disease (AD) and in a control group using the GAT-1 selective radioligand [3H]tiagabine. Post mortem brain tissue from frontal cortex, temporal cortex, and caudate nucleus from 18 AD patients and 23 age-matched controls were studied. The binding was saturable (Kd 26 nM) and region specific. There were no significant differences between the groups with respect to the binding capacity (Bmax) and binding affinity (Kd). The unaltered [3H]tiagabine binding to GAT-1 protein indicates that intrinsic GABA neurons are spared in Alzheimer's disease.
    Type of Medium: Electronic Resource
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  • 10
    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
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