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  • 1
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The learning process of imprinting involves morphological, electrophysiological and biochemical changes in a region of the chick (Gallus gallus domesticus) forebrain known as the intermediate and medial part of the hyperstriatum ventrale (IMHV). The alterations include increases in the mean length of postsynaptic density profiles of axospinous synapses and the number of N-methyl-d-aspartate (NMDA) receptor binding sites, and changes in spontaneous and evoked electrical activity. Recent immunocytochemical and behavioural studies have suggested that inhibitory GABAergic neurotransmission plays a role in learning. In this context, it has previously been reported that a novel avian γ-aminobutyric acid (GABA) type A (GABAA) receptor gene, encoding the γ4 subunit, is highly expressed in the hyperstriatum ventrale. In this study, we have used in situ hybridization to map, in detail, the expression of the γ4-subunit gene in the chick brain, and to assess the effect of imprinting training on the level of the corresponding transcript. Our results reveal that the γ4-subunit mRNA has a restricted distribution, and demonstrate a highly significant, time-dependent effect of training on its steady-state level. At 10 h but not at 5 h after training there is a decrease (25–32%) in the amount of this transcript in parts of the medial hyperstriatum ventrale, including the IMHV. A decrease (28–39%) is also seen in certain visual and auditory pathway areas but no effect was observed in other forebrain regions such as the hyperstriatum intercalatus superior (HIS). These results suggest that imprinting training leads to a time-dependent down-regulation of GABAergic transmission, and raise the possibility that this down-regulation plays a role in learning.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    ISSN: 1365-2524
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Young people with disabilities are often excluded from the labour market. The present paper describes an evaluation of an innovative 2-year pilot initiative called Vocational Opportunities in Training for Employment (VOTE) implemented in Northern Ireland to provide employment training and support for vulnerable young adults with a wide range of disabilities. The principal aims of the study were to assess the impact of the new service in the extent to which: (1) it had created and developed training and employment opportunities for young people; and (2) promoted inclusive working partnerships. Documentary analysis was used as a basis for describing and assessing the project objectives in combination with face- to-face interviews with a small number of key stakeholders. A total of 122 young people participated in the initiative in the pilot period, during which time 160 qualifications were obtained. Key stakeholders expressed positive views about the initiative, and in particular, its therapeutic benefits and the extent of interagency working and shared learning. The VOTE initiative achieved considerable success in enabling a significant proportion of young adults to engage in society by developing social and employment skills, and by improving their employment opportunities and prospects. Factors critical to the continued success of this and similar initiatives include: the close involvement of parents; addressing the concerns of local employers; the sympathetic treatment of workplace issues; and effective partnership working.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Peripheral corticotropin-releasing factor (CRF) receptor ligands inhibit gastric acid secretion and emptying while stimulating gastric mucosal blood flow in rats. Endogenous CRF ligands are expressed in the upper gastrointestinal (GI) tissues pointing to local expression of CRF receptors. We mapped the distribution of CRF receptor type 1 (CRF1) and 2 (CRF2) in the rat upper GI. Polyclonal antisera directed against the C-terminus of the CRF receptor protein were generated in rabbits and characterized by western blotting and immunofluorescence using CRF1- and CRF2-transfected cell lines and in primary cultured neurons from rat brain cortex. A selective anti-CRF1 antiserum (4467a-CRF1) was identified and used in parallel with another antiserum recognizing both CRF1 and CRF2 (4392a-CRF1&2) to immunostain gastric tissue sections. Antiserum 4467a-CRF1 demonstrated specific immunostaining in a narrow zone in the upper oxyntic gland within the stomach corpus. Conversely, 4392a-CRF1&2 labeled cells throughout the oxyntic gland and submucosal blood vessels. Pre-absorption with the specific antigen peptide blocked immunostaining in all experiments. Doublestaining showed co-localization of 4392a-CRF1&2 but not 4467a-CRF1 immunoreactivity with H/K-ATPase and somatostatin immunostaining in parietal and endocrine cells of the oxyntic gland. No specific staining was observed in the antrum with either antisera, whereas only antiserum 4392a-CRF1&2 showed modest immunoreactivity in the duodenal mucosa. Finally, co-localization of CRF2 and urocortin immunoreactivity was found in the gastric glands. These results indicate that both CRF receptor subtypes are expressed in the rat upper GI tissues with a distinct pattern and regional differences suggesting differential function.
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  • 4
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Using the inactivation of mitochondrial and cytosolic aconitases as markers of compartment-specific superoxide (O2−) production, we show that oxygen-glucose deprivation (OGD) or excitotoxin exposure produce a time-dependent inactivation of mitochondrial, but not cytosolic, aconitase in cortical cultures. To determine if mitochondrial O2− production was an important determinant in neuronal death resulting from OGD, metalloporphyrins with varying superoxide dismutase (SOD) activity were tested for their ability to protect against mitochondrial aconitase inactivation and cell death. OGD-induced mitochondrial aconitase inactivation and cell death was inhibited by manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP), manganese tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) and NMDA receptor antagonists. By contrast, NMDA- or kainate (KA)-induced mitochondrial aconitase inactivation and cell death was inhibited by MnTBAP, but not MnTE-2-PyP. Moreover, both MnTBAP and MnTE-2-PyP penetrated mitochondrial fractions of cortical cells. These data suggest that mitochondrial aconitase inactivation closely correlates with subsequent neuronal death following excitotoxicity produced by OGD or NMDA/KA exposure. Assessment of biological rather biochemical antioxidant activities better predicted neuroprotection by metalloporphyrins. Moreover, antioxidants that protect oxidant-sensitive mitochondrial targets such as aconitase may be useful as therapies for disease states involving excitotoxicity.
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  • 5
    Electronic Resource
    Electronic Resource
    350 Main St , Malden , MA 02148 , USA , and PO Box 1354, Garsington Rd , Oxford OX4 2DQ , UK and PO Box 378 Carlton South , 3053 Victoria , Australia . : Blackwell Science Ltd
    Journal of prosthodontics 14 (2005), S. 0 
    ISSN: 1532-849X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Purpose: The purpose of this study was to compare the linear dimensional accuracy and the handling characteristics of 7 die materials. Materials and Methods: A master die analogous to a complete veneer crown preparation was machined from medical grade stainless steel, and 3 measurements (1: vertical; 2 and 3: horizontal) were made from 3 scribed reference lines. Individual polyvinylsiloxane impressions were made (n = 10) for each of the specimens. The fabricated dies were measured (50×) to the nearest 0.0001 mm. Data were subject to ANOVA/Duncan tests at significance level 0.05 and pairwise comparisons. Results: Type IV resin-impregnated dental stone and copper-plated dies most closely approximated the dimensions of the master die, and were not significantly different from each other in any of the pairwise comparisons. Conventional Types IV and V dental stone dies exhibited setting expansion within the range appropriate for gypsum. Epoxy resin die materials demonstrated shrinkage comparable to the expansion of the Types IV and V dies. Polyurethane dies displayed a combination of linear expansion and shrinkage. Bis-acryl composite resin dies had excessive shrinkage. Conclusions: Type IV resin-impregnated dental stone and copper-plated dies were more dimensionally accurate than the other die materials tested.
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Insulin-like growth factor-1 (IGF-1) plays important roles in the developing and mature retina and in pathological states characterized by retinal neovascularization, such as diabetic retinopathy. The effects of IGF-1 on glucose transport and proliferation and the signal transduction pathways underlying these effects were studied in a primary bovine retinal endothelial cell (BREC) culture model. IGF-1 stimulated uptake of the glucose analog 2-deoxyglucose in a dose-dependent manner, with a maximal uptake at 25 ng/mL (3.3 nm) after 24 h. Increased transport occurred in the absence of an increase in total cellular GLUT1 transcript or protein. IGF-1 stimulated activity of both protein kinase C (PKC) and phosphatidylinositol-3 kinase (PI3 kinase), and both pathways were required for IGF-1-mediated BREC glucose transport and thymidine incorporation. Use of a selective inhibitor of the β isoform of PKC, LY379196, revealed that IGF-1 stimulation of glucose transport was mediated by PKC-β; however, inhibition of PKC-β had no effect on BREC proliferation. Taken together, these data suggest that the actions of IGF-1 in retinal endothelial cells couple proliferation with delivery of glucose, an essential metabolic substrate. The present studies extend our general understanding of the effects of IGF-1 on vital cellular activities within the retina in normal physiology and in pathological states such as diabetic retinopathy.
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Presenilin-1 (PS1), implicated as the active component of the γ-secretase enzymatic complex, is known to cleave the cell surface receptor Notch1 after ligand binding. Here we directly visualize Notch1–PS1 interactions using a novel fluorescence lifetime imaging microscopy assay to monitor fluorescence resonance energy transfer. We demonstrate that endogenous Notch1 and PS1 move into close proximity at the cell surface after activation of Notch1 by the Delta1 ligand. A constitutively active N-terminally truncated form of Notch1, an immediate substrate of the γ-secretase complex, similarly is found in close proximity to PS1. Interestingly, this interaction remains in the presence of a potent γ-secretase active site inhibitor. Thus ligand binding to Notch1 appears to result in access of truncated Notch1 to a putative docking site on the PS1–γ-secretase complex. These results suggest a novel mechanism of ligand binding-mediated signal transduction of Notch1.
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  • 8
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In order to maintain normal metabolism, the neuroretina is completely dependent on the constant delivery of glucose across the retinal microvascular endothelial cells comprising the inner blood–retinal barrier. Glucose uptake into these cells is influenced by various stimuli, including hypoxia and growth factors. Recently, insulin-like growth factor-1 (IGF-1) was shown to enhance retinal endothelial glucose transport in a process that is dependent on protein kinase C (PKC) and phosphatidylinositol-3 kinase (PI3 kinase). In the current study, the role of mitogen-activated protein kinase (MAP kinase) in regulating IGF-1 effects on retinal endothelial cell glucose transport was investigated in a bovine retinal endothelial cell (BREC) culture model. IGF-1 (25 ng/mL) caused a rapid increase in MAP-kinase activity and ERK phosphorylation. Inhibition of MAP kinase with PD98059 (100 µm) blocked IGF-1 enhancement of 2-deoxyglucose uptake. In order to clarify the relationship between PKC, PI3 kinase and MAP kinase in IGF-1 signaling in retinal endothelial cells, the effects of selective inhibitors of MAP kinase (PD98059), PKC (GF109203X), and PI3 kinase (wortmannin, LY294002) on signal transduction by IGF-1 were studied. Inhibition of MAP kinase abolished IGF-1 stimulation of PKC but had no effect on PI3 kinase activity, whereas inhibition of either PKC and PI3 kinase had no effect on MAP kinase phosphorylation or activity in IGF-1-treated cells. Taken together, these data demonstrate that IGF-1 stimulation of BREC glucose transport requires activation of MAP kinase and that MAP kinase is upstream from PKC but is independent of PI3 kinase in mediating the actions of IGF-1 on retinal endothelial cells.
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  • 9
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: N-Methyl-d-aspartate (NMDA) receptors mediate increases in intracellular calcium that can be modulated by protein kinase C (PKC). As PKC modulation of NMDA receptors in neurons is complex, we studied the effects of PKC activation on recombinant NMDA receptor-mediated calcium rises in a nonneuronal mammalian cell line, human embryonic kidney 293 (HEK-293). Phorbol 12-myristate 13-acetate (PMA) pretreatment of HEK-293 cells enhanced or suppressed NMDA receptor-mediated calcium rises based on the NMDA receptor subunit composition. NR2A or NR2B, in combination with NR1011, conveyed enhancement whereas NR2C and NR2D conveyed suppression. The PKC inhibitor bisindolylmaleimide blocked each of these effects. The region on NR2A that conveyed enhancement localized to a discrete segment of the C terminus distal to the portion of NR2C that is homologous to NR2A. Calcium-45 accumulation, but not intracellular calcium store depletion, matched PMA effects on NMDA receptor-mediated calcium changes, suggesting that these effects were not due to effects on intracellular calcium stores. The suppression of intracellular calcium transients seen with NR2C was eliminated when combined with NR1 splice variants lacking C-terminal cassette 1. Thus, the intracellular calcium effects of PMA were distinguishable based on both the NR1 splice variant and the NR2 subunit type that were expressed. Such differential effects resemble the diversity of PKC effects on NMDA receptors in neurons.
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Pediatric anesthesia 12 (2002), S. 0 
    ISSN: 1460-9592
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Urinary retention occurring after caudal anaesthesia in children has a low incidence. Most children will void within 12 h of surgery, although the incidence of retention is higher after hypospadias repair. However, overdistention causing bladder atony that is temporary, or may become permanent, is described in adults. Long-term effects of overdistention in children have not been described. Urine volume, used to describe overdistention, is traditionally measured after catheterization.We report two children suffering from urine retention after caudal anaesthesia (bupivacaine 0.25%) was used to supplement a general anaesthetic. Ultrasound bladder monitoring was used to assist with the clinical diagnosis of bladder distension in the postanaesthesia care unit (PACU) and subsequent management.In–out catheterization was required in a 1-year-old-girl with a bladder volume of 12 ml·kg−1 after external manual compression over the bladder was unable express urine. Spontaneous micturation occurred within the subsequent 8 h. A 10-year-old boy suffered distress in PACU with a bladder volume, measured by ultrasound, of 5 ml·kg−1. Catheterization relieved distress and spontaneous micturation returned 18 h after surgery. Measured urine volumes were similar to those estimated by ultrasound.Ultrasound bladder monitoring is a simple, noninvasive technique that can be used to assist with the diagnosis and management of urinary retention in children. It may replace catheterization as the prefered technique to measure urine volume. The correlation between measured bladder volumes and urine volume appears reasonable. A volume of approximately 10 mg·kg−1 may be considered as causing overdistension.
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