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  • 1
    ISSN: 1432-2072
    Keywords: GM1 ; Haloperidol ; Glutamate synapses ; Perforated PSD ; Striatum ; Dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Haloperidol, a typical antipsychotic drug, causes an increase in the mean percentage of synapses within the striatum containing a discontinuous, or perforated, postsynaptic density (PSD) following 1 month of treatment (Meshul et al. 1994). This effect is not observed with the atypical antipsychotic drug, clozapine, following subchronic administration (Meshul et al. 1992a). This morphological change is also associated with an increase in the density of dopamine D2 receptors. The synapses containing the perforated PSD are asymmetrical and the nerve terminals contain the neurotransmitter, glutamate, as demonstrated by immunocytochemistry. We have also shown that subchronic treatment with haloperidol (0.5 mg/kg per day, 30 days) results in a decrease in the density of glutamate immunoreactivity within asymmetric nerve terminals associated with perforated and non-perforated PSDs (Meshul and Tan 1994). This could be due to an increase in glutamate release, perhaps due to activation of corticostriatal synapses. Agnati et al. (1983a) reported that administration of GM1 ganglioside blocks the increase in dopamine D2 receptors following haloperidol treatment. GM1 has also been shown to attenuate the release of glutamate (Nicoletti et al. 1989). In order to determine if similar treatment with ganglioside could block the haloperidol-induced ultrastructural changes noted above, rats were coadministered GM1 (10 mg/kg per day) and haloperidol (0.5 mg/kg per day) for 30 days. We report that GM1 blocked the haloperidol-induced increase in striatal asymmetric synapses containing a perforated PSD, but had no effect on the increase in dopamine D2 receptors or the decrease in nerve terminal glutamate immunoreactivity. GM1, either alone or co-administered with haloperidol, also caused a small, but significant, increase in the density of all asymmetric synapses within the striatum. It is possible that the effect of GM1 in attenuating the haloperidol-induced change in glutamate synapses with perforated PSDs is primarily postsynaptic, since GM1 did not block the change in density of glutamate immunoreactivity within asymmetric nerve terminals.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Haloperidol ; Vacuous chewing movements ; Glutamate synapses ; Perforated postsynaptic density ; Striatum ; Tardive dyskinesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term treatment with the typical antipsychotic drug, haloperidol, can lead to a sometimes irreversible motor disorder, tardive dyskinesia (TD). It has been hypothesized that increased release of glutamate due to prolonged neuroleptic drug treatment may result in an excitotoxic lesion in specific neuronal populations within the basal ganglia, leading to TD. We reported that treatment with haloperidol for 1 month results in an increase in the mean percentage of striatal asymmetric synapses containing a perforated postsynaptic density (PSD) and that these synapses are glutamatergic. Using quantitative immunocytochemistry, we found that depending on how long the animals had been off haloperidol following subchronic (30d) treatment, there was either a decrease (1 day off) or increase (3–4 days off) in the density of glutamate immunolabeling within the presynaptic terminals of synapses with perforated PSDs. Using a rat model for TD, animals in the current study were treated for 1 year with haloperidol and spontaneous oral dyskinesias (i.e. vacuous chewing movements, VCMs) were recorded. In these long-term treated animals we wanted to determine if there was a correlation between glutamate function, as measured by changes in synapses with perforated PSDs and the density of nerve terminal glutamate immunoreactivity, and VCM behavior. In drug treated rats which demonstrated either a high or low rate of VCMs, there was a significant increase in the mean percentage of asymmetric synapses in the dorsolateral striatum with perforated PSDs in both haloperidol-treated groups compared to vehicle-treated rats. There was a small but significant increase in the density of glutamate immunolabeling within striatal nerve terminals of the high VCM group compared to the low VCM group. There was, however, no difference in the density of glutamate immunolabeling between the high VCM group compared to the vehicle-treated animals. One reason for this lack of difference was partially due to a significant increase in nerve terminal area within the high VCM group compared to either the low VCM- or vehicle-treated groups. The larger nerve terminal size in the high VCM group may be due to a small but sustained increase in glutamate neurotransmitter release with the ability of the terminal to maintain its supply of glutamate, while the terminals in the low VCM group showed evidence of glutamate depletion. This finding would be consistent with the hypothesis that increased glutamatergic activity may be associated with TD.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 274 (1993), S. 135-144 
    ISSN: 1432-0878
    Keywords: Trophoblast ; Uterus ; Veins ; Basement membrane ; Placenta ; Macaca fascicularis (Primates) ; Macaca mulatta (Primates)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Trophoblast cells invade and modify the uterine vasculature to provide circulation of maternal blood through the placenta. Although evidence indicates fundamental differences between trophoblast modification of arteries and veins, interactions between trophoblast cells and uterine veins have not been addressed. In this report we describe the processes by which trophoblast cells invade and restructure uterine veins during placentation in the macaque. Antibodies were used to identify trophoblast, endothelium, and basement membranes. During early gestation, trophoblast migrated from the trophoblastic shell and, by intravasation, replaced portions of the wall and endothelium of veins in the vicinity of the shell; this is in contrast to invasion by extravasation reported for the arteries in this species. These areas had discontinuous endothelial basement membranes and the endothelial cells were variably hypertrophied. Deeper portions of veins were not invaded; this too is in contradistinction to the spiral arteries where trophoblastic modification extends to the myometrial segments. Later in gestation, those portions of veins interacting with trophoblast were contained within the trophoblastic shell or situated such that one side abutted the shell. These regions of the veins were lined by endothelium, but it could not be determined whether this represented re-endothelialization of regions formerly lined by trophoblast or if these endothelial cells were never displaced.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0878
    Keywords: Trophoblast ; Placenta ; Laminin ; Collagen ; Fibronectin ; Extracellular matrix,-structures ; Macaca fascicularis (Primates)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The cytotrophoblastic cell columns and trophoblastic shell of macaque placentas accumulate progressively greater amounts of intercellular material during early gestation. We studied the composition of this material in placentas collected from 22–34 days of gestation by using immunoperoxidase techniques directed to the extracellular matrix molecules fibronectin, type IV collagen, and laminin. These antigens co-localized within the intercellular deposits at all stages studied. At day 22 the proximal cell columns were composed of cells with narrow interstices and which lacked immunoreactivity for the 3 antigens. Distally the cells were vacuolated and the intercellular spaces increased in size and contained dense matrix deposits. The trophoblastic shell consisted of closely packed, non-vacuolated cytotrophoblast cells with only a delicate meshwork of matrix. By day 27 the matrix deposits of the distal cell columns increased markedly in size. The trophoblastic shell contained larger numbers of vacuolated cells and was occupied by accumulations of matrix. By 34 days the matrix deposits of the cell columns expanded substantially along the longitudinal axes of the columns. These deposits were often continuous with a matrix-dense, cell-deficient layer in the trophoblastic shell. This matrix-rich zone lay between a cellular layer adjacent to the intervilous space and a similar, but discontinuous, cell layer that formed the junctional zone with the endometrium.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York : Wiley-Blackwell
    Biopolymers 6 (1968), S. 1-25 
    ISSN: 0006-3525
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The kinetics of biopolymerization on nucleic acid templates is discussed. The model introduced allows for the simultaneous synthesis of several chains, of a given type, on a common template, e.g., the polyribosome situation. Each growth center [growing chain end plus enzyme(s)] moves one template site at a time, but blocks L adjacent sites. Solutions are found for the probability nj(t) that a template has a growing center that occupies the sites j  -  L + 1,…, j at time t. Two special sets of solutions are considered, the uniform-density solutions, for which nj(t) = n, and the more general steady-state solutions, for which dnj(t)/dt = 0. In the uniform-density case, there is an upper bound to the range of rates of polymerization that can occur. Corresponding to this maximum rate, there is one uniform solution. For a polymerization rate less than this maximum, there are two uniform solutions that give the same rate. In the steady-state case, only L = 1 is discussed. For a steady-state polymerization rate less than the maximum uniform-density rate, the steady-state solutions consist of either one or two regions of nearly uniform density, with the density value(s) assumed in the uniform region(s) being either or both of the uniform-density solutions corresponding to that polymerization rate. For a steady-state polymerization rate equal to or slightly larger than the maximum uniform-density rate, the steady-state solutions are nearly uniform to the single uniform-density solution for the maximum rate. The boundary conditions (rate of initiation and rate, of release of completed chains from the template) govern the choice among the possible solutions, i.e., determine the region(s) of uniformity and the value(s) assumed in the uniform region(s).
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Applied Polymer Science 18 (1974), S. 709-725 
    ISSN: 0021-8995
    Keywords: Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: The radiation-induced polymerization of methyl methacrylate was investigated with radiation sources of cobalt 60 and accelerated electrons at dose rates up to 3 Mrads/sec. Extrapolation of previous rates of polymerization at dose rates of 0.01-200 rads/sec coincided with the present results, the rates being approximately proportional to the square root of the dose rate throughout the entire set of dose rates measured. The molecular weights seemed to be independent of dose rate at the highest dose rates investigated. A combination of high polymer with a much higher molecular weight than expected was formed, together with a substantial portion of low molecular weight polymer. The reason for this behavior is not clear at this time. The G(M·) calculated from the molecular weights and fraction of polymer and resin was 6.0, which approaches that reported in previous investigations at low dose rates. There was no significant effect of air on the polymerization kinetics of methyl methacrylate at above 1 Mrad/sec. Nitrogen also did not influence the measured rates. Conversions to polymer were not substantially reduced by the presence of inhibitor at above 1.26 × 105 rads/sec. Water did not influence the rates of polymerization, except at the highest temperature (50°C) investigated. A large posteffect was observed in sealed degassed ampoules after 25% conversion to polymer. Only 3.4% additional polymer was formed in 24 hr after irradiation in the presence of air. The activation energy for the electron beam polymerization of methyl methacrylate was about 7.0 kcal/mole. This value, considering the complications in technique such as beam heating, did not differ from literature data enough to suggest any mechanistic difference in the polymerization at high dose rates.
    Additional Material: 13 Ill.
    Type of Medium: Electronic Resource
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