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  • Achromatopsia  (2)
  • Apolipoprotein E  (2)
  • Autoreceptors  (2)
  • 1
    ISSN: 1364-6753
    Schlagwort(e): Key words Alzheimer disease ; Apolipoprotein E ; Low-density lipoprotein receptor-related protein ; LRP1 gene ; Chromosome 12
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: ABSTRACT The low-density lipoprotein receptor-related protein gene (LRP1) is often mentioned as a candidate gene for Alzheimer disease (AD) because of its role as a receptor for apolipoprotein E (apoE), a major genetic risk factor for late-onset familial and sporadic AD. A recent association study of a tetranucleotide repeat polymorphism located 5′ to the LRP1 gene detected an increase in the 87 base pair allele in AD cases compared to unaffected controls. Additionally, an independent study involving a genomic screen for genes associated with late-onset AD identified a region as a possible location of a late-onset AD gene on chromosome 12p between D12S373 and D12S390, about 10 cM proximal to LRP1. We examined 144 late-onset multiplex AD families, 436 sporadic AD cases, and 240 controls and found no evidence of linkage or association of LRP1 and AD. Our data indicate that genetic variation of the LRP1 gene is not a major risk factor in the etiology of AD.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1364-6753
    Schlagwort(e): Key words HLA ; Apolipoprotein E ; Alzheimer disease
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: ABSTRACT The apolipoprotein E (APOE)-4 allele is a major risk factor for late-onset Alzheimer disease (AD), but it does not account for all the genetic variation in late-onset AD; thus, other genetic markers must be examined. Previous studies suggest an HLA-A2 allele association with risk and earlier onset age of AD. Because these effects may be additive to those of APOE-4, we studied HLA-A2 and APOE-4 frequencies in AD patients and cognitively intact controls. A total of 712 unrelated Caucasian subjects included 479 patients with AD (435 sporadic, 44 familial) and 233 controls. Patients (mean±SD age 73.9±7.9 years, range 42–93 years) had probable AD, according to standard diagnostic criteria; controls (mean±SD age 70.4±8.5 years, range 37–92 years) were cognitively intact. APOE and HLA-A2 typing used polymerase chain reaction to indicate the number of APOE-4 alleles present as well as the presence (A1/A2, A2/A2 genotypes) or absence (A1/A1 genotype) of HLA-A2. A two-way analysis of variance was used to assess the effect of the HLA-A2 allele on age at onset of dementia. No association between HLA-A2 and APOE-4 was found, and the presence of HLA-A2 allele did not increase AD risk. There was also no evidence for an association between HLA-A2 and earlier onset age of AD. Examination age, sex, family history of AD, and recruitment site had no influence on these results. In conclusion, the HLA-A2 allele did not influence AD risk or onset age in this study population. A2 heterozygosity, and population differences, including stratification sub-structures, and other undetermined factors could contribute to discrepant findings among studies.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-1912
    Schlagwort(e): Key words Microdialysis ; 5-HT release ; Chronic antidepressant ; Citalopram ; 5-HT reuptake inhibitor ; Tolerance ; Autoreceptors ; Frontal cortex ; Dorsal hippocampus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rats were administered the selective serotonin (5-HT) uptake blocker citalopram or saline for 14 days to determine if prolonged treatment would lead to changes in extracellular 5-HT or autoreceptor sensitivity. One day after drug withdrawal, dialysis probes were implanted in the frontal cortex and dorsal hippocampus. Dialysis experiments were carried out using chloral hydrate anesthetized rats. The experimental protocol comprised the administration of three consecutive drug challenges: (1) After stable baseline levels were obtained, citalopram was infused through the dialysis probes to locally block uptake in the forebrain. (2) Subsequently, a 5-HT1B receptor agonist (RU24969 or CP93,129) was infused through the probe to test for changes in terminal autoreceptor sensitivity. (3) Last, citalopram was administered systemically to test the effect of indirect activation of somatodendritic autoreceptors. Under these conditions, with uptake already blocked locally in the forebrain, systemic citalopram produces a decrease in extracellular 5-HT, an effect that can be inhibited by pretreatment with antagonists of 5-HT1A receptors. The results indicate that during local infusion of citalopram extracellular 5-HT was significantly higher in the dorsal hippocampus of the chronic citalopram as compared to saline treatment group. This difference persisted throughout the full time course of the experiment. However, the decreases in 5-HT levels produced by local infusion of a 5-HT1B receptor agonist or after systemic citalopram administration were not significantly different between the chronic citalopram and saline treated groups. There were no significant differences between chronic citalopram and saline treated animals in frontal cortex. These results suggest that prolonged inhibition of 5-HT uptake may produce a selective change in the regulation of release from median raphe 5-HT neurons, but this change could not be clearly linked to a change in nerve terminal or somatodendritic autoreceptor sensitivity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    ISSN: 1432-1912
    Schlagwort(e): Microdialysis ; 5-HT release ; Chronic antidepressant ; Citalopram ; 5-HT reuptake inhibitor ; Tolerance ; Autoreceptors ; Frontal cortex Dorsal hippocampus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Rats were administered the selective serotonin (5-HT) uptake blocker citalopram or saline for 14 days to determine if prolonged treatment would lead to changes in extracellular 5-HT or autoreceptor sensitivity. One day after drug withdrawal, dialysis probes were implanted in the frontal cortex and dorsal hippocampus. Dialysis experiments were carried out using chloral hydrate anesthetized rats. The experimental protocol comprised the administration of three consecutive drug challenges: (1) After stable baseline levels were obtained, citalopram was infused through the dialysis probes to locally block uptake in the forebrain. (2) Subsequently, a 5-HT1B receptor agonist (RU24969 or CP93,129) was infused through the probe to test for changes in terminal autoreceptor sensitivity. (3) Last, citalopram was administered systemically to test the effect of indirect activation of somatodendritic autoreceptors. Under these conditions, with uptake already blocked locally in the forebrain, systemic citalopram produces a decrease in extracellular 5-HT, an effect that can be inhibited by pretreatment with antagonists of 5-HT1A receptors. The results indicate that during local infusion of citalopram extracellular 5-HT was significantly higher in the dorsal hippocampus of the chronic citalopram as compared to saline treatment group. This difference persisted throughout the full time course of the experiment. However, the decreases in 5-HT levels produced by local infusion of a 5-HT1B receptor agonist or after systemic citalopram administration were not significantly different between the chronic citalopram and saline treated groups. There were no significant differences between chronic citalopram and saline treated animals in frontal cortex. These results suggest that prolonged inhibition of 5-HT uptake may produce a selective change in the regulation of release from median raphe 5-HT neurons, but this change could not be clearly linked to a change in nerve terminal or somatodendritic autoreceptor sensitivity.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Documenta ophthalmologica 37 (1974), S. 119-144 
    ISSN: 1573-2622
    Schlagwort(e): Achromatopsia ; visual threshold ; dark adaptation ; photopic and scotopic mechanisms ; spectral luminous efficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract In three of the five achromats examined psychophysically, evidence of three plateaux was found at certain areas of the retina during the normally photopic phase of dark adaptation while the scotopic plateau was normal. These high intensity plateaux coincided fairly well with the photopic phase of our standard dark adaptation curve and the fourth plateau with its scotopic phase. This points to three photopic submodalities and to a normal scotopic mechanism in these achromats. However, the spectral sensitivities, both in the retinal periphery and in the fovea, were maximal between 500 nm and 510 nm for the three photopic plateaux and for the scotopic one and fitted satisfactorily with the 1951 CIE scotopic standard. The mechanisms underlying the appearance of the up to three fast, high-intensity plateaux in the achromats' dark adaptation curves do not fulfill normal requirements completely since they are photopic as to the kinetics of their recovery and scotopic as to their spectral luminous efficiency. The data from the subjects examined indicate three types of receptors with cone kinetics during dark adaptation but containing rhodopsin. The theoretical significance of the findings is discussed, especially why rhodopsin seems to regenerate faster in cones than in rods or in the test tube. Other cases were found, one only illustrated, with only one fast high-intensity plateau similar to those described in the literature.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    Documenta ophthalmologica 37 (1974), S. 79-117 
    ISSN: 1573-2622
    Schlagwort(e): Achromatopsia ; rod monochromatism ; nystagmus ; photophobia ; color vision tests ; ERG recovery during dark adaptation ; ERG photopic components ; scotopic components ; photopic activity in purely scotopic ERGs ; ERG as function of intensity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract 39 patients suffering from congenital achromatopsia were investigated by various methods, including electroretinography, during both light and dark adaptation. This condition was typically expressed by the presence of photophobia, low visual acuity, nystagmus and various degrees of ametropia. The fundus was normal in 9 cases. Most of the other cases showed various macular or foveal abnormalities. 24 patients showed complete absence of color vision, and practically all displayed the ‘scotopic line’ in the Farnsworth Panel D-15 test. The electroretinogram (ERG) was almost always extinct in light. In the dark, in most patients the ERG displayed the scotopic mechanism solely, but some ERGs indicated subnormal photopic components either at the beginning or during all dark adaptation. This presence of photopic activity in the ERG of achromats was verified by 2 additional experiments. In one, the recovery of the positive wave of four achromats was compared on a percentage scale with that of four normal subjects and found to be similar, although the slightly faster course in achromats indicates less photopic activity than in normals. In the second, the positive amplitudes of the ERGs of 12 achromats with purely scotopic ERGs were recorded at completed dark adaptation as function of increasing stimulus intensities, all above the photopic threshold, and compared with those of 16 normal subjects. The amplitudes increased linearly with the 1.2 log intensity range in both groups, though the slope of the curve of the achromats was 1/4 that of the normals. In another experiment, the positive wave of the ERG, as elicited by light over 5 log units in the scotopic range, was found in an achromat to be of very similar shape as that of a normal, indicating scotopic acitivity to be similar in both subjects. The fact that, nevertheless, photopic components were not demonstrable in most ERGs, despite present photopic activity, can be explained by the relatively insensitive electrical method coupled with the subnormality of the retinal photopic mechanism in every achromat.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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