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  • 1
    Electronic Resource
    Electronic Resource
    Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: immunological aspects, spontaneous and drug-induced behaviour, and dopamine release (1988)
    Springer
    Experimental brain research 70 (1988), S. 192-208 
    Details
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Spontaneous behaviour ; Human fetus ; Dopamine release ; Intracerebral dialysis ; Immunization Cyclosporin A ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have used a rat model of Parkinson's disease (PD) to address issues of importance for a future clinical application of dopamine (DA) neuron grafting in patients with PD. Human mesencephalic DA neurons, obtained from 6.5–8 week old fetuses, were found to survive intracerebral cell suspension xenografting to the striatum of rats immunosup-pressed with Cyclosporin A. The grafts produced an extensive new DA-containing terminal network in the previously denervated caudate-putamen, and they normalized amphetamine-induced, apomorphine-induced and spontaneous motor asymmetry in rats with unilateral lesions of the mesostriatal DA pathway. Grafts from an 11.5-week old donor exhibited a lower survival rate and smaller functional effects. As assessed with the intracerebral dialysis technique the grafted DA neurons were found to restore spontaneous DA release in the reinnervated host striatum to normal levels. The neurons responded with large increases in extracellular striatal DA levels after the intrastriatal administration of the DA-releasing agent d-amphetamine and the DA-reuptake blocker nomifensine, although not to the same extent as seen in striata with an intact mesostriatal DA system. DA fiber outgrowth from the grafts was dependent on the localization of the graft tissue. Thus, grafts located within the striatum gave rise to an extensive axonal network throughout the whole host striatum, whereas grafted DA neurons localized in the neocortex had their outgrowing fibers confined within the grafts themselves. In contrast to the good graft survival and behavioural effects obtained in immunosuppressed rats, there was no survival, or behavioural effects, of human DA neurons implanted in rats that did not receive immunosuppression. In addition, we found that all the graft recipients were immunized, having formed antibodies against antigens present on human T-cells. This supports the notion that the human neurons grafted to the non-immunosuppressed rats underwent immunological rejection. Based on an estimation of the survival rate and extent of fiber outgrowth from the grafted human fetal DA neurons, we suggest that DA neurons that can be obtained from one fetus may be sufficient to restore significant DA neurotransmission unilaterally, in one putamen, in an immunosuppressed PD patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00271860
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of xamoterol after intravenous and oral administration to volunteers (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 469-473 
    Details
    ISSN: 1432-1041
    Keywords: xamoterol ; cardiac failure ; beta1-adrenoceptor partial agonist ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of xamoterol, a β-adrenoceptor partial agonist under clinical evaluation for the treatment of mild to moderate heart failure, have been studied in 12 healthy male subjects. They received 14 mg i.v. and oral doses of 50 and 200 mg as a tablet and 200 mg as a solution in a 4 way cross-over design. After i.v. dosing the elimination half-life was 7.7 h, the total body clearance was 224 ml·min−1 and the volume of distribution at steady-state (Vss) was 48 l. Sixty-two percent of the dose was recovered unchanged in urine. After oral doses, the absolute bioavailability of xamoterol was shown to be 5% irrespective of whether the dose was administered as a tablet or solution. Peak plasma concentrations occurred at about 2 h for the tablet dose and slightly earlier (1.4 h) for the solution. Peak plasma concentration, AUC and urinary recovery of unchanged drug increased in proportion to dose. The apparent elimination half-life after oral doses (16 h) was significantly longer than that observed after an intravenous dose. Despite the low bioavailability, the degree of inter-subject variability of oral bioavailability was small probably indicating that the controlling factor is the hydrophilic nature of the molecule rather than extensive first pass metabolism or poor dissolution of xamoterol from the tablet formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01046704
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  • 3
    Electronic Resource
    Electronic Resource
    Grain Boundaries in Polycrystalline Ceramics (1987)
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Materials Research 17 (1987), S. 57-74 
    Details
    ISSN: 0084-6600
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1146/annurev.ms.17.080187.000421
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  • 4
    Electronic Resource
    Electronic Resource
    Host Corticostriatal Fibres Establish Synaptic Connections with Grafted Striatal Neurons in the Ibotenic Acid Lesioned Striatum (1989)
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 1 (1989), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The connections between host corticostriatal afferents and neurons in intrastriatal grafts of foetal striatal tissue have been studied with electron microscopic immunocytochemistry using Phaseolus vulgaris leucoagglutinin (PHA-L) as a label of the host corticostriatal fibres. Adult rats with unilateral ibotenic acid lesions of the head of the caudate putamen received foetal cell suspension grafts from E14–15 rat embryos into the lesioned striatal area. Ten months after transplantation, multiple iontophoretic injections of PHA-L were made into the host frontal cortex. These injections labelled large numbers of corticostriatal fibres which extended across the graft - host border to form a rich axonal network mainly in the peripheral portions of the grafts. At the ultrastructural level a total of 134 PHA-L-labelled terminals were identified to form asymmetric synaptic contacts with neurons within the grafts. Of these contacts, 83% were in contact with dendritic spines, 12% with dendritic shafts, and 5% with small shafts or spines. The synaptic contacts were similar to those identified in intact regions of the host striatum that were spared by the lesion. However, the synapses in the host striatum were almost exclusively in contact with spines (98%). These results demonstrate that the corticostriatal projection, which constitutes a major source of afferent control in the normal striatum, not only extends axons into the intrastriatal striatal grafts, but also establishes synaptic connections with the implanted neuronal elements.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1460-9568.1989.tb00787.x
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  • 5
    Electronic Resource
    Electronic Resource
    Synaptogenesis of Grafted Cholinergic Neurons (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 495 (1987), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1987.tb23680.x
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  • 6
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    Corneille's Differences with the Seventeenth-Century Doctrinaires over the Moral Authority of the Poet (1985)
    Cambridge : Periodicals Archive Online (PAO)
    The Modern language review. 80:3 (1985:July) 550 
    Details
    ISSN: 0026-7937
    Topics: Linguistics and Literary Studies
    URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pao:&rft_dat=xri:pao:article:0094-1985-080-03-000003
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  • 7
    Electronic Resource
    Electronic Resource
    High-temperature deformation of a polycrystalline alumina containing an intergranular glass phase (1985)
    Springer
    Journal of materials science 20 (1985), S. 1321-1332 
    Details
    ISSN: 1573-4803
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract The high-temperature creep and flexural deformation of a model alumina-glass ceramic is reported over the temperature range in which the glass phase softens (from a viscosity of ~107 to ~103 P). Under both loading conditions the deformation is accompanied by extensive cavitational damage throughout the material. The cavitation is inhomogeneously distributed and at high stresses can be localized into bands. In addition, crack propagation at high temperature results in the formation of a cavitational zone on either side of the fracture and measurements of its size are presented as a function of deformation temperature. On the basis of the microstructural observations of the deformed material, the sequence by which isolated cavities grow and link up prior to failure, is described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01026328
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  • 8
    Electronic Resource
    Electronic Resource
    Human fetal dopamine neurons grafted in a rat model of Parkinson's disease: ultrastructural evidence for synapse formation using tyrosine hydroxylase immunocytochemistry (1988)
    Springer
    Experimental brain research 73 (1988), S. 115-126 
    Details
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Dopamine neurons ; Human fetus ; Tyrosine hydroxylase immunocytochemistry ; Synaptic contacts ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Human fetal mesencephalic dopamine (DA) neurons, obtained from 6.5–9 week old aborted fetuses, were grafted to the striatum of immunosuppressed rats with 6-hydroxydopamine lesions of the ascending mesostriatal DA pathway. The effects on amphetamine-induced motor asymmetry were studied at various timepoints after grafting. At eight weeks, functional graft effects were not evident but after 11 weeks small effects on motor asymmetry could be monitored and rats tested 19–21 weeks after grafting exhibited full reversal of the lesion-induced rotational behaviour. Four rats were sacrificed at different timepoints between 8 and 20 weeks and the grafted DA neurons were studied in tyrosine hydroxylase (TH) immunocytochemically stained sections at the light and electronmicroscopic level. The grafts contained a total of 500–700 TH-positive neurons in each rat. In one rat sacrificed 8 weeks after grafting the grafted neurons were TH-positive but exhibited virtually no fiber outgrowth. In another rat, sacrificed after 11 weeks, a sparse TH-positive fiber plexus was seen to extend into the adjacent host neostriatum. Two rats sacrificed after 20 weeks both contained TH-positive neurons that gave rise to a rich fiber network throughout the entire host neostriatum, and this fiber network was also seen to extend into the globus pallidus and nucleus accumbens. Very coarse TH-positive processes, identified as dendrites in the electron microscope, projected up to 1.5–2.0 mm from the graft into the host striatum. Ultrastructural analysis revealed that the grafted neurons had formed no TH-positive synaptic contacts with host striatal neurons after 8 weeks, and at 11 weeks some few TH-positive synapses were identified. Twenty weeks after transplantation, abundant TH-positive synaptic contacts with host neurons were seen throughout the neostriatum, and such contacts were identified in the globus pallidus as well. Thus, the present study provides tentative evidence for a time-link between the development of synaptic contacts and the appearance of functional graft effects. Similar to the normal mesostriatal DA pathway, ingrowing TH-positive axons formed symmetric synapses and were mainly seen to contact dendritic shafts and spines. However, in comparison to the normal rat striatum there was a higher incidence of TH-immunoreactive boutons forming synapses onto neuronal perikarya. The TH-positive dendrites that extended into the host striatum were seen to receive non-TH-immunoreactive synaptic contacts, presumably arising from the host neurons. These results suggest that human fetal DA neurons are able to develop a reciprocal synaptic connectivity with the host rat when grafted to the adult brain. Grafting of human fetal DA neurons may therefore be expected to provide a means of restoring regulated synaptic DA release in patients with Parkinson's disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279666
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  • 9
    Electronic Resource
    Electronic Resource
    Evidence for a receptor mediated action of norepinephrine distinct from alpha- and beta-adrenoceptors (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 261-266 
    Details
    ISSN: 1432-1912
    Keywords: Norepinephrine ; UK-14,304-18 ; St 587 ; Benextramine ; Adrenoceptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The mode of action of (-) norepinephrine (NE) and UK-14,304-18 has been investigated using the chohnergically-evoked ‘twitch’ response of the electrically stimulated guinea-pig ileum. St 587 and benextramine were employed as antagonists. St 587 acted as a competitive antagonist toward UK-14,304-18, yielding an apparent pA2 value of 7.3. In contrast, St 587 failed to act competitively toward NE. Similarly, benextramine (1×10−5 mol/l) blocked the inhibitory responses to UK-14,304-18 but was considerably less active toward NE. Remaining responses to NE after benextramine were not antagonized by St 587, even at a concentration of 3×10−5 mol/l. It is postulated that NE acts to inhibit the ‘twitch’ response be evoking two different receptor-mediated events: 1. agonism at the alpha2-adrenoceptor and 2. agonism at a site which is distinct from the alpha- and beta-subtypes. In the concentrations studied, UK-14,304-18, St 587 and benextramine age postulated to lack affinity for the proposed site. The effect of NE and UK-14,304-18 was also investigated on the contractile responses to exogenously applied histamine. These experiments were done in the presence of muscarinic cholinergic and adrenoceptor blockade. NE inhibited responses to histamine but UK-14,304-18 was inactive. Furthermore, the inhibitory action of NE was stereoselective with the (-) form being 25 times more potent than the (+) enantiomer. These findings suggest the presence of a receptor site for NE which is distinct from cholinergic mechanisms and established alpha and beta-adrenoceptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508780
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  • 10
    Electronic Resource
    Electronic Resource
    An inhibitory prejunctional 5-HT1-like receptor in the isolated perfused rat kidney (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 332 (1986), S. 8-15 
    Details
    ISSN: 1432-1912
    Keywords: Perfused rat kidney ; 5-Hydroxytryptamine ; 5-Hydroxytryptamine agonists ; 5-Hydroxytryptamine antagonists ; 5-Hydroxytryptamine receptors ; Prejunctional 5-HT1-like receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study has identified a receptor for 5-hydroxytryptamine (5-HT) which functions to inhibit the stimulus-induced release of [3H] noradrenaline following sympathetic periarterial nerve stimulation to the isolated perfused rat kidney. In addition to 5-HT (IC30=4.5×10−8 mol/l), both 5-carboxamidotryptamine (IC30=8×10−9 mol/l) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl) indole (RU-24969, IC30=2.5×10−7 mol/l) acted as agonists whereas 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was inactive. The inhibitory effect of 5-HT on the electrically-evoked release of tritium was antagonized in a concentration-dependent manner by methiothepin (IC50=4×10−9 mol/l), metergoline (IC50=4×10−8 mol/l) and methysergide (IC50=1.3×10−7 mol/l) but not by cyproheptadine, ketanserin, mesulergine, (−)-propranolol, (±)-pindolol, (±)-cyanopindolol, metoclopramide or phentolamine. It is concluded that the receptor to 5-HT conforms to general criteria defining 5-HT1-like receptors but at the present time the receptor site cannot be fitted to the designated 5-HT1A, 5-HT1B or 5-HT1C subtypes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00633190
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