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  • 1
    ISSN: 1573-6903
    Keywords: [35S]GTPγS ; autoradiography ; rat ; brain ; guanine nucleotides ; GTPases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The binding of [35S]GTPγS was characterised with autoradiography in rat brain. The binding was saturable, but the rate of dissociation was very slow. Analysis of binding isotherms revealed one class of binding sites with a Kd of 0.8 μM. The specific binding was 98%. Different guanine nucleotides were all able to compete with [35S]GTPγS binding. However, no displacement was seen by the ATP-analogue App[NH]p, indicating that [35S]GTPγS does not bind to ATP-sites. Autoradiograms showed a highly homogenous distribution of [35S]GTPγS binding, in grey as well as in white matter. However, the pattern changed dramatically in the presence of GTP, which, unlike the non-hydrolysable GTP-analogues Gpp[NH]p and GTPγS, did not displace [35S]GTPγS binding throughout the brain. In white matter areas the binding was potently displaced, while in many grey matter areas, e.g., the striatum, the binding was seen to increase. This GTP-induced increase in [35S]GTPγS binding was strongly Mg2+-dependent, with an optimum at 10 mM. This, together with the finding that the regional effects of GTP correspond well to previously reported distribution of low Km GTPase, suggest that the levels of binding of [35S]GTPγS in the presence of GTP may reflect functional G-protein activity.
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  • 2
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A recently described procedure of freezing and thawing, which allows retention of metabolic and functional integrity, has been applied in the study of serotonin and dopamine uptake into frozen rat and post mortem human frozen tissue. TheK m andV max for the serotonin uptake into human hypothalamus were estimated to be 0.12 μM and 0.03 nmol/g/min respectively. TheK m andV max for the dopamine uptake into human putamen were estimated to be 0.28 μM and 0.13 nmol/g/min respectively. The results indicate that the freezing procedure does not affect the uptake sites for these transmitters. The storage time before freezing is however of importance for theV max value. TheK m value for the uptake, on the other hand, seems to be rather resistant to storage time before freezing.
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  • 3
    ISSN: 1573-4919
    Keywords: Alzheimer's disease ; receptors ; G-proteins. adenylyl cyclase ; phosphoinositide breakdown ; inositol (1,4,5)-trisphosphate ; protein kinase C ; β-amyloid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Many of the treatments directed towards alleviation of symptoms in Alzheimer's disease assume that target receptor systems are functionally intact. However, there is now considerable evidence that this is not the case. In human post-mortem brain tissue samples, the function of the GTP-binding protein Gs in regulating adenylyl cyclase is severely disabled, whereas that of Gi is intact. This difference in the function of the two G-protein types is also found in G-protein regulation of high- and low-affinity receptor recognition site populations. Measurement of G-protein densities using selective antibodies has indicated that the dysfunction in Gs-stimulation of cAMP production correlates with the ratio of the large to small molecular weight isoforms of the Gsα subunit. With respect to intracellular second messenger effects, there is a dramatic decrease in the density of brain receptor recognition sites for Ins(1,4,5)P3 that is not accompanied by a corresponding change in the Ins(1,3,4,5)P4 recognition site density. Protein kinase C function is also altered in Alzheimer's disease, a finding that may be of importance for the control of β-amyloid production. These studies indicate that signal transduction processes are severely compromised in Alzheimer's disease. Some of these disturbances are also seen in cultured fibroblasts from Alzheimer's disease patients, indicating that they are neither restricted to areas of histopathological change, nor non-specific changes found late in the course of the disease. Cellular models to investigate the relation between amyloid production and deficits in signal transduction are also discussed.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    BioMetals 13 (2000), S. 311-317 
    ISSN: 1572-8773
    Keywords: cadmium ; blood pressure ; BMI ; cognitive function ; elderly
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Concentration of cadmium in blood in an elderly population with a mean age of 87 years was studied in relation to age, blood pressure, BMI, cognitive function, gender and smoking. This population-based study consisted of 804 subjects both men and women. Clinical examination included medical and social history, physical and neurologic examination, and assessment of cognitive functions with Mini-Mental State Examination (MMSE). Information on prescription and non-prescription drug use was collected. Anti-hypertensive drugs included all medicines potentially used for treating high blood pressure. Blood pressure was measured. Whole blood from 763 subjects was analysed for cadmium by atomic absorption spectrophotometry (GFAAS) with Zeeman background correction and with a graphite furnace using the L'vov platform technique including quality control. Differences in cadmium concentrations were related to non- smokers (3.9 nmol/l), previous smokers (4.4 nmol/l) and current smokers (7.5 nmol/l). There were no relations between cadmium and age, blood pressure or cognitive functions. In conclusion, increased cadmium levels were found in smokers. A possible contribution from previous occupational exposure needs to be further evaluated.
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  • 5
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The interaction of the substrate-selective irreversible inhibitor J-508 [N-methyl-N-propargyl-(1-indanyl)-ammonium hydrochloride] with the B form of human brain monoamine oxidase has been investigated, and the conditions necessary for this inhibitor to “titrate” the concentration of this enzyme form determined. It was found that the concentration of monoamine oxidase-B determined in this way was the same when either benzylamine or β-phenethylamine was used to assay for activity, which would indicate that this enzyme form is not heterogeneous. Furthermore, the variation in activity from sample to sample was found to be due to a variation in the concentration of available monoamine oxidase-B active centers, rather than due to a variation in the molecular turnover numbers of this enzyme form towards its amine substrates.
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  • 6
    ISSN: 1432-1106
    Keywords: Alzheimer's disease ; Cortical layers ; Ibotenic acid ; Muscarinic receptor subtypes ; Nucleus basalis magnocellularis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cholinergic system in the central nervous system is an important component of the neural circuitry of learning, memory and cognition. A decline of cholinergic innervation in the human brain is a characteristic feature of dementia of Alzheimer's type. In this study, changes in cholinergic markers were studied after a unilateral lesion of the nucleus basalis magnocellularis (nbM). Acetylcholinesterase (AChE) histochemistry showed a loss of cortical AChE-containing neurons, and choline acetyltransferase (ChAT) immunohistochemistry demonstrated a loss of cholinergic cells in nbM. The localizations of muscarinic Ml and M2 receptors using [3H]pirenzepine ([3H]PZ) and [3H]AF-DX 384, respectively, were studied by quantitative autoradiography 1, 2, 4 and 6 weeks following unilateral ibotenic acid lesion of nbM. A significant decrease in [3H]PZ binding sites was observed at postlesion week 1 in the parietal and temporal cortices. The decrease in [3H]AF-DX 384 binding sites on the lesioned side was observed throughout frontal, parietal and temporal cortices after postlesion week 1, with a significant increase after 6 weeks, possibly as result of loss of presynaptic receptors and upregulation of postsynaptic ones. Moreover, laminar distribution after nbM lesion shows that M1 and M2 receptor binding sites are more affected in superficial layers (I,II,III) than in the deep layers (IV,V,VI), depending on ligand, postlesion period and cortical region. Furthermore, nbM lesion causes a higher deficit of M2 receptors than of M1 receptors. These data suggest the existence of a presynaptic population as well as a postsynaptic population of M1 and M2 receptors which are differently affected after unilateral nbM lesion.
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  • 7
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This study was planned to determine the number of origins of the mutation underlying Huntington's disease (HD) in Sweden. Haplotypes were constructed for 23 different HD families, using six different polymorphisms [(CCG) n , GT70, 674, BS1, E2 and 4.2], including two within the gene. In addition, extensive genealogical investigations were performed, and the geographical origin of the haplotypes was studied. Ten different haplotypes were observed suggesting multiple origins for the HD mutation in Sweden. Analysis of the two polymorphic markers within the HD gene (the CCG repeat and GT70) indicates that there are at least three origins for the HD mutation in Sweden. One of these haplotypes (7/A) accounts for 89% of the families, suggesting that the majority of the Swedish HD families are related through a single HD mutation of ancient origin. Furthermore, three of the families that were previously considered to be unrelated could be traced to a common ancestor in the 15th century, a finding that is consistent with this hypothesis.
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  • 8
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Mutations at codon 717 in exon 17 of the β–amyloid precursor protein (APP) gene have previously been shown to segregate with early onset Alzheimer's disease in some families. We have identified a double mutation at codons 670 and 671 (APP 770 transcript) in exon 16 which ...
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  • 9
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
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  • 10
    ISSN: 1434-0879
    Keywords: Genital tuberculosis ; male ; experimental tuberculosis ; spread of genital tuberculosis ; experimental model-guinea pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spread of experimentally induced tuberculosis in the male genital organs was studied in guinea pigs. 40 animals were inoculated with H37Rv into the epididymis or seminal vesicle. Half of the animals in each series were prepared by resection of the ductus deferens before inoculation. — Canalicular, haematogenous and lymphatic spread are discussed. It is concluded that lymphatic spread is possible and often occurs.
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