bluuebunny/crossref_metadata_2025 huggingface dataset:
Death of septal cholinergic neurons produced by chronic exposure to glutamate is prevented by the noncompetitive NMDA receptor/channel antagonist, MK‐801: Role of nerve growth factor and nitric oxide
Authors: Michel P. P. , Agid Y.
Published: January 2005

To study the sequence of degenerative events possibly associated with cholinergic cell death in Alzheimer's disease, septal cholinergic neurons derived from rat embryonic brains were exposed to chronic excitotoxic stress by glutamate. Counts of choline acetyltransferase (ChAT)‐immunopositive neurons and measurement of ChAT activity revealed that concentrations of glutamate on the order of 70 μM killed 50% of cholinergic neurons after 24 hr of treatment. Neurotoxic effects were not aimed at cholinergic neurons specifically, since other populations of cells present in these cultures were also affected at similar concentrations. The noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor channel antagonist MK‐801 (10 μM) abolished acute neuronal swelling and rescued from late degeneration both cholinergic and non‐cholinergic cells when concentrations of glutamate up to 500 μM were added to the cultures. Protective effects declined progressively with increasing concentrations of the amino acid, even when MK‐801 was raised to its highest nontoxic levels, e.g., 50 μM. The kainate/quisqualate receptor antagonist CNQX provided no protection alone or in combination with MK‐801. Nerve growth factor (NGF), used in standard culture conditions to stimulate the expression of the cholinergic phenotype, was shown not to influence excitotoxic neurodegenerative changes. Several observations suggested that nitric oxide (NO) may act as an intercellular messenger of NMDA‐mediated cell death in septal cultures: (1) Most of the cholinergic neurons contained the NO synthase enzyme as characterized by NADPH‐diaphorase (NADPH‐d) staining; (2) sodium nitroprusside (SNP) [a chemical with the ability of generating NO] was capable of mimicking some of the aspects of the glutamate‐induced degenerative process; (3) the rise in cyclic GMP which was observed in the presence of toxic levels of glutamate and which is usually taken as an index of NO production, was antagonized by MK‐801 and by the inhibitor of the NO synthase enzyme, L‐NOARG. Yet, the fact that L‐NOARG and its congener, L‐NAME, were ineffective in preventing glutamate‐induced neurodegenerative changes in our culture system did not substantiate our working hypothesis. Altogether these results suggest that glutamate‐induced cholinergic neuronal death is the consequence of an overstimulation of NMDA receptors and that neither NGF nor NO plays a key role in the degenerative process. © 1995 Wiley‐Liss, Inc.
Regeneration of specific nerve cells in lesioned visual cortex of the human brain: An indirect evidence after constant stimulation with different spots of light
Authors: Potthof R. D.
Published: January 2005

The defective parts of the visual field of two braininjured patients were stimulated with different spots of light. There is evidence for at least five independent visual functions which can be restored due to constant stimulation of the blind part of the visual field: (1) The constant stimulation of the blind part of the visual field with spots of white light leads to an increase of the visual field for the perception of white light only. (2) The constant stimulation with spots of light of different wavelengths leads to an increase of the visual field for different color perception. To enlarge the visual field for the perception of the color red, a light stimulus with the wavelength of 656 nanometers (nm) was used; for the visual field for the perception of the color green 525 nm; for yellow 578 nm; and for blue 450 nm. (3) The constant stimulation of the blind visual field with black and white light bars of different orientations and constellations leads to an increase of the foveal acuity and an improvement of form perception in the periphery of the visual field.

The results suggest that the recovery of visual functions, different color perception and form perception, may depend upon neuronal regeneration in the human visual cortex; regeneration occurs with adequate and constant stimulation of its specific neurons. © 1995 Wiley‐Liss, Inc.
Site‐directed mutagenesis of human CNTF: Functional analysis of recombinant variants
Authors: Thier M. , Simon R. , Krüttgen A. , Rose‐John S. , Heinrich P. C. , Schröder J. M. , Weis J.
Published: January 2005

Ciliary neurotrophic factor (CNTF), interleukin‐6 (IL‐6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) share functional properties, a predicted common helical framework, and partially identical receptor components. CNTF is a survival promoting factor for various types of neurons in vitro and in vivo. In the present study, structural features essential for the biological function of human CNTF were investigated. Several recombinant CNTF variants were constructed by PCR and expressed in E.coli. Their survival promoting activities were determined using cultures of embryonic chick and newborn rat dorsal root ganglion cells. Deletion of 14 N‐terminal and 18 C‐terminal amino acids significantly increased bioactivity compared to wild‐type (wt) CNTF. Further truncation of the CNTF molecule at the N‐ or C‐terminus resulted in a significant reduction or complete loss of activity. Substitution of two amino acids (Lys154Glu and Trp157Pro) abolished the survival promoting effect. Recently described analogous substitutions in IL‐6 had resulted in a partial IL‐6 receptor antagonist. However, the double substitution variant had no significant inhibitory effect on wtCNTF activity in assays with both wt and mutant factor. The CNTF variants constructed had almost identical effects on both chick and rat neurons indicating a close similarity of the avian and the mammalian CNTF receptor complex. The present results also demonstrate that a core segment of the CNTF molecule is indispensable for biological function. Analogous segments important for activity have already been identified in the related molecules IL‐6, LIF, and OSM. Thus, our data confirm the close structural relationship of CNTF to these “neuropoietic” cytokines. In addition, they demonstrate that site‐directed mutagenesis of recombinant human CNTF can yield molecules which show increased survival promoting activity on mammalian neurons. © 1995 Wiley‐Liss, Inc.
Axonal atrophy in aging is associated with a decline in neurofilament gene expression
Authors: Parhad I. M. , Scott J. N. , Cellars L. A. , Bains J. S. , Krekoski C. A. , Clark A. W.
Published: January 2005

Neurofilaments (Nfs) are major determinants of axonal caliber. Nf transcript levels increase during development and maturation, and are associated with an increase in Nf protein, Nf numbers, and caliber of axons. With aging there is axonal atrophy. In this study we asked whether the axonal atrophy of aging was associated with a decline in Nf transcript expression, Nf protein levels, and Nf numbers. Expression of transcripts for the three Nf subunits was evaluated in dorsal root ganglia (DRG) of Fischer‐344 rats aged 3–32 months by Northern and in situ hybridization. There was an approximately 50% decrease in Nf subunit mRNA levels in DRG of aged (>23 months) as compared to young and mature (3 and 12 months) rats, whereas expression of another neuronal mRNA, GAP‐43, showed no decline. Western analysis showed a corresponding decrease in Nf subunit proteins and no decline in GAP‐43. Morphometric analysis showed a 50% decrease in Nf numbers within axons. The decrease in Nf gene expression and Nf numbers was accompanied by a decrease in cross‐sectional area and circularity of all myelinated fibers, with the largest fibers showing the most marked changes, and a shrinkage in the perikaryal area of large neurons. Furthermore, we found a concomitant decrease in the expression of transcripts for the nerve growth factor receptors trkA and p75 with aging. Although the mechanisms leading to the decrease in Nf gene expression with aging are not known, a decrease in the availability of growth factors, or the neuron's ability to respond to them, may play a role in this process. © 1995 Wiley‐Liss, Inc.
Bilateral gliosis in unilaterally lesioned septohippocampal system: Changes in GFAP immunoreactivity and content
Authors: Jegliński W. , Koczyk D. , Zaremba M. , Oderfeld‐Nowak B.
Published: January 2005

Unilateral damage to the lateral fimbria led to a bilateral gliosis in the septum and hippocampus. The gliosis was manifested by an increase in GFAP staining, accompanied by an increased number of glial fibrillary acidic protein (GFAP)(+) cells and GFAP content; the latter however was not visible in the contralateral septum. In general, the contralateral reaction appeared weaker than the ipsilateral one.

The pattern of contralateral increase in GFAP‐immunoreactivity (IR) matched almost exactly that observed on the ipsilateral side in the hippocampus (the most evident increase was seen in the oriens and pyramidal layers of cornu Ammonis 3 and in polymorphie area of gyros dentatus). In the septum the bilateral increase in GFAP‐IR was mainly visible in the dorsolateral quadrant of the structure; however in the ipsilateral side it spread over the whole half of the structure.

The astrocytic responses in the septum and hippocampus were not equivalent: they differed mainly with regard to the increase of GFAP(+) cells (over 300% of control in the anterior part of the septum and only about 120% in the dorsal hippocampus). The differences between astrocytic response in the septum and hippocampus were also manifested by different relations between the percentage increases of other gliotic indices: GFAP‐IR and GFAP content.

Various possibilities that may account for the occurrence of contralateral gliosis are discussed, the most plausible being the contribution of interhemispheric and intraseptal links and the action of some diffusible agents. We suggest that bilateral gliosis may have an impact on compensatory postlesion processes, possibly by providing trophic support to impaired neurons. © 1995 Wiley‐Liss, Inc.
Glutamate‐induced antigenic changes of phospholipase C‐δ in cultured cortical neurons
Authors: Shimohama S. , Akaike A. , Tamura Y. , Matsushima H. , Kume T. , Fujimoto S. , Takenawa T. , Kimura J.
Published: January 2005

Phosphoinositide‐specific phospholipase C (PLC) is a key enzyme in signal transduction. It was previously demonstrated that an antibody to an isozyme of PLC, PLC‐δ, produces intense staining of neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores and neuropil threads in the brains of patients with Alzheimer's disease (AD). Although the etiology of neuronal degeneration in AD is still to be defined, excitotoxic glutamate might be a candidate. In the present study, an anti‐PLC‐δ antibody was used to examine the influence of glutamate on PLC‐δ immunoreactivity in cultured rat cortical neurons. Exposure to glutamate caused the death of cultured cortical neurons and exhibited increased immunostaining with the anti‐PLC‐δ antibody. Subtoxic doses of glutamate also increased PLC‐δ immunoreactivity in a dose‐dependent manner. Both glutamateinduced neuronal degeneration and the increases in PLC‐δ immunoreactivity were prevented by removal of extracellular Ca2+ or the application of an N‐methyl‐D‐aspartate (NMDA) receptor antagonist, MK801. The glutamate‐induced increase in PLC‐δ immunoreactivity was also prevented by Nω‐nitro‐Larginine, a nitric oxide (NO) synthase inhibitor. These results suggest that NO formation secondary to Ca2+ influx by NMDA receptor activation leads to similar modifications of PLC‐δ to those seen in AD. © 1995 Wiley‐Liss, Inc.
Studies on T‐cell receptors involved in experimental autoimmune encephalomyelitis using the complementary peptide recognition approach
Authors: Xian C. J. , Simmons R. D. , Willenborg D. O. , Vandenbark A. A. , Hashim G. A. , Carnegie P. R.
Published: January 2005

Based upon Blalock's complementary recognition approach, a complementary or antisense peptide (CP) was designed to the experimental autoiramune encephalomyelitis (EAE) epitope peptide, rat myelin basic protein (MBP) peptide 72‐82. This peptide (EAE CP) was shown to have some sequence similarities to T‐cell receptors (TCR) and MHC II molecules in a sequence homology search. Solid‐phase binding as‐says demonstrated specific and high affinity binding (3 and 4 μM) between the EAE CP and the rat and guinea pig EAE epitope peptides (Rt72‐82 and Gp69‐82), respectively. This EAE CP was also found to be immunogenic in rats in an ear swelling test for delayed type hypersensitivity (DTH) reactions and an ELISA for antibody responses. However, a rabbit antibody generated to EAE CP was shown to be unable to stain the Vβ8+ EAE susceptible T‐cells in immunofluorescence analyses. This EAE CP was also used in attempts to down‐regulate EAE and the results showed that prior immunization with EAE CP in complete Freund's adjuvant could not prevent the Lewis rats from developing EAE. Although the data on sense‐antisense peptide interaction were positive and the EAE CP was immunogenic, the inability of EAE CP to regulate EAE indicates that the CP approach may not be generally applicable. © 1995 Wiley‐Liss, Inc.
Mitogn induced proliferation of isolated adult mouse schwann cells
Authors: Zhang B. T. , Hikawa N. , Horie H. , Takenaka T.
Published: January 2005

The proliferation of neonatal Schwann cells (SCs) in response to mitogenic agents has been well analyzed in vitro, but a limited range of mitogens have been defined. We investigated whether three identified neonatal SC mitogens [glial growth factor (GGF), platelet‐derived growth factor BB (PDGF‐BB), and basic fibroblast growth factor (bFGF)] are required to stimulate mitosis of adult SCs. Adult SCs were isolated from mouse sciatic nerves by mechanical and chemical dissociation, following three experimental steps: (1) culturing the dissociated cells for 24 hr in 10% FCS‐F12 medium, (2) culturing these cells in serum‐free medium for the next 48 hr, and (3) purifying adult SCs by differential adhesion. We describe a new method for preparation of SCs from peripheral nerves of adult mouse that provides 99.5% pure SCs populations at cell yields of greater than 3 × 103 cells/mg of starting nerve wet weight within 5 culture days. Although mitosis of SCs in culture in response to mitogens requires the presence of serum, the complex nature of serum renders difficult a complete analysis of mitogens required for SCs DNA synthesis, so we examined the proliferating response of adult SCs to GGF, PDGF‐BB, and bFGF in serum‐free medium. GGF alone had mitogenicity for adult SCs in a dose‐dependent manner, and synergistic activation coupling with forskolin was not observed. Neither PDGF‐BB nor bFGF was mitogenic for adult SCs when used alone or with forskolin. Measurement of intracellular cyclic AMP levels in SCs cultured with these growth factors showed that cAMP levels were not changed by GGF and bFGF, and PDGF‐BB reduced the cAMP level to half of basal one. This study demonstrated that adult SCs could proliferate without serum factors and forskolin in response to GGF, and adult SCs were activated by GGF through a signal transduction pathway separate from the cyclic AMP‐dependent system. In addition, PDGF‐BB or bFGF has no mitogenic effect on adult SCs under serum‐free conditions. © 1995 Wiley‐Liss, Inc.
Noradrenaline‐induced stimulation of glutamine metabolism in primary cultures of astrocytes
Authors: Huang R. , Hertz L.
Published: January 2005

Effects of noradrenaline and of adrenergic subtype specific agonists on the uptake and metabolism of [14C]glutamine and [14C]glutamate in primary cultures of mouse astrocytes have been investigated. The total uptake of radioactivity from extracellular [14C]glutamine into the cells was enhanced during exposure to 100 μM noradrenaline, isoproterenol, or clonidine. This is partly dag to an increased radioactivity in the glutamile pool and partly due to an increased formation of labeled glutamate from glutamine, which had become very marked (66%) after 240 min of incubation. The CO2 formation from labeled glutamine during 4 hr of incubation was enhanced about twofold in the presence of noradrenaline. Ten millimolar amino oxyacetic acid (AOAA), a transamination inhibitor, had no effect on CO2 formation from glutamine, indicating that the formation of α‐ketoglutarate from glutamate occurs as an oxidative deamination. The stimulation of 14CO2 production from labeled glutamine was at least as large when glucose was deleted from medium, suggesting that the increased 14CO2 formation represents a stimulation of glutamine metabolism as such and is not only a reflection of an increase in oxidative metabolism of glucose and a bidirectional exchange between α‐ketoglutarate and glutamate. The opposite process, incorporation of radioactivity from labeled glutamate into glutamine, was not enhanced in the presence of noradrenaline. The findings suggest that noradrenaline stimulates the rates of glutamine uptake, glutamate synthesis, and CO2 production from glutamine and thus increases energy supply to astrocytes but has no effect on the opposite reaction, i.e., glutamine formation from glutamate, a reaction of importance for neuronal‐astrocytic interations. © 1995 Wiley‐Liss, Inc.
Early neuroblasts are pluripotential: Colocalization of neurotransmitter and neuropeptides
Authors: Kentroti S. , Vernadakis A.
Published: January 2005

This study was undertaken in order to establish the presence of pluripotential neuroblasts in the developing chick CNS. This has been suggested by our previous observations that expression of emerging neuronal phenotypes in the chick embryo CNS is affected by exposure to neurotrophic substances (i.e., GHRH, SRIF, NGF, EGF, muscle‐derived factors) or neurotoxins such as ethanol. We have proposed that one mechanism whereby these substances elicit their effects is by shifting phenotypic expression in populations of pluripotential neuroblasts. In order to establish the presence of significant populations of pluripotential neuroblasts, cultures obtained from 3‐day‐old whole chick embryos (E3WE) were doublestained with antibodies to markers specific for four neuronal phenotypes in various permutations. Cultures at 6 DIV were tested for the presence of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), γ‐aminobutyric acid (GABA), and somatostatin (SRIF) alone, and in various combinations. We observed a colocalization of all phenotypic markers within neuronal perikarya and processes in more than fifty percent of neuronal cells in these cultures. These data suggest that developing neuroblasts at this stage of embryogenesis possess the machinery necessary to adopt multiple neuronal phenotypes. The colocalization of neurotransmitter proteins in early neuroblasts (60 hr of embryogenesis) supports the recent concept that these substances themselves may influence phenotypic expression and also supports our idea that microenvironmental factors (i.e., ethanol, growth factors) provide signals which affect emerging phenotypes. © 1995 Wiley‐Liss, Inc.
Hydrocortisone influences voltage‐dependent L‐type calcium channels in cultured human skeletal muscle
Authors: Braun S. , Sarkozi E. , McFerrin J. , Askanas V.
Published: January 2005

The glucocorticoid hydrocortisone (HC), applied for up to 2 weeks to either aneurally or innervated cultured human muscle, produced 2‐fold increase of the number of dihydropyridine ([3H]PN200‐110) binding sites. The K+ ‐induced, nifedipine‐inhibited Ca2+ uptake was increased 40%. The effect of HC was concentration‐ and time‐dependent. [3H]PN200‐110 affinity for its receptor was not affected by HC treatment. HC did not exert significant influence on the total amount of protein, CK activity, and the number of myotubes. These results indicate that voltage‐dependent L‐type Ca2+ channel expression in human muscle is regulated by glucocorticoid. © 1995 Wiley‐Liss, Inc.
Reinnervation of a denervated slow muscle triggers high extrajunctional expression of the asymmetric molecular forms of acetyicholinesterase
Authors: Črne‐Finderle N. , Toplišek J. , Sketelj J.
Published: January 2005

Expression of acetylcholine receptor and of the asymmetric molecular forms of acetylcholinesterase (AChE) in the extrajunctional regions of rat muscles is suppressed during early postnatal development. In mature muscles, the extrajunctional synthesis of acetylcholine receptor, but not of the asymmetric molecular forms of AChE, becomes reactivated after denervation. The hypothesis that a denervated muscle needs reinnervation in order to revert transiently to an immature state characterized by high extrajunctional production of the asymmetric AChE forms, was examined in rat muscles recovering after nerve crush. Molecular forms of AChE were analysed by velocity sedimentation. Activity of the asymmetric A12 AChE form in the extrajunctional regions of the slow soleus (SOL) muscle increased during the first week after reinnervation to about 9 times its control level, remained high for about one week, and declined towards normal thereafter. If the nerve was crushed close to the muscle and reinnervation occured very rapidly, the extrajunctional increase of the A12 AChE form still occured but was less pronounced than after late reinnervation. In contrast, a transient paralysis of the SOL muscle due to acetylcholine receptor blockade by α‐bungarotoxin, followed by spontaneous recovery of muscle activity after 3–5 days, did not revert AChE regulation into an immature state. Disuse of the SOL muscle caused by leg immobilization, which is known to change the tonic pattern of neural stimulation of the SOL muscle into a phasic one, did not prevent the reversion of AChE regulation during reinnervation. This indicates that neural stimulation pattern is not crucial for this reversion. In contrast to slow SOL, the fast extensor digitorum longus muscle did not revert to an immature state in respect to AChE regulation after reinnervation. This muscle type‐specific response may be due to intrinsic differences between the myogenic cells of slow and fast muscle fibres. © 1995 Wiley‐Liss, Inc.
Inhibition of the ATP‐sensitive potassium channel in the guinea pig substantia nigra by BMS 181100 is not mediated by a sigma‐binding site
Authors: O'Callaghan J. F. X. , Greenfield S. A.
Published: January 2005

Quantitative autoradiography of brain tissue has revealed a high density of binding sites for the K‐ATP channel antagonists, the sulphonylureas, and for σ‐ligands in the substantia nigra (SN). In view of the high density of the two binding sites in the SN the possibility has been investigated that the K‐ATP channel and the σ‐binding site are functionally linked. The K‐ATP channel‐mediated membrane hyperpolarisation and decrease in input resistance produced by hypoxia and by the metabolic inhibitor, cyanide, in rostral substantia nigra pars compacta neurons are antagonised by the σ‐ligand BMS 181100. In addition, BMS 181100 antagonises activation of the K‐ATP channel by diazoxide; cromakalim is found to be without effect in these neurons. Antagonism of the cyanide‐induced hyperpolarisation is dose dependent and is observed at concentrations of the drug which have no observable effect on the resting membrane properties of the neurons. By contrast, the nonselective sigma ligands 1,3‐di‐O‐tolylguanidine (10 μM) and ( +)‐3‐(3‐hydroxyphenyl)‐N‐(1 ‐propyl)piperidine (100 μM), and the selective σl‐ligand (+)‐pentazocine 5‐10 μM) have no effect on the cyanide‐induced hyperpolarisation. 5‐HT (50‐100 μM) and the selective 5‐HT1A receptor agonist 8‐OH‐DPAT (50 μM) also fail to antagonise the cyanideinduced hyperpolarisation. The antagonism of the cyanide‐induced hyperpolarisation by BMS 181100 persists in the presence of tetrodotoxin (1 μM) and in the presence of high concentrations of (+)‐3‐(3‐hydroxyphenyl)‐N‐(1‐propyl)piperidine, but not under conditions of reduced calcium (0.1‐0.2 mM) and raised magnesium (6 mM) concentrations, which block synaptic transmission. It is concluded that in substantia nigra phasic neurons the σ‐binding site does not regulate activation of the ATP‐sensitive channel. However, BMS 181100 antagonises K‐ATP channel activation in these neurons independently of σ‐binding sites and 5‐HT receptors. This action of BMS 181100 is TTX insensitive and Ca2+ dependent. © 1995 Wiley‐Liss, Inc.
Developmental regulation of Thy 1.2 rate of synthesis in the mouse cerebellum
Authors: Radrizzani M. , Carminatti H. , Pivetta O. H. , Vargas V. P. Idoyaga
Published: January 2005

Thy 1.2 is a well‐known major cell surface glycoprotein of the central nervous system (CNS). However, the regulation of the expression of this molecule as well as its function are yet to be determined. To approach these problems we studied the synthesis of the molecule in the developing cerebellum of wild‐type and staggerer mutant mice. We found the appearance of a [35S]‐methionine‐labeled band detected with specific Sepharose 4B‐bound monoclonal antibodies (Mabs). The Thy 1.2 activity increases progressively from postnatal day 9 (P9), reaching the highest rate at P12, subsequently decreasing sharply at P13, and remaining relatively low up to P16 in the wild type. Comparison of these data to the rates of total protein synthesis reveals a selective developmental regulation of Thy 1.2 expression, at least at the translational level. This correlates quite well with the timing of synaptic stabilization between parallel fibers and Purkinje cell dendritic spines. Furthermore, at P12 Thy 1.2 protein is preferentially located in the synaptosomal fraction. The parallel fiber:Purkinje cell synapsis is not stabilized in the staggerer mutant mouse. At P12 Thy 1.2 synthesis is 30% of the wild type, indicating that the translational regulation of Thy 1.2 is altered in the staggerer mutation. © 1995 Wiley‐Liss, Inc.
Characterization of synaptic vesicles and related neuronal features in nerve growth factor and ras oncogene differentiated PC12 cells
Authors: Tao‐Cheng J.‐H. , Dosemeci A. , Bressler J. P. , Brightman M. W. , Simpson D. L.
Published: January 2005

PC12 cells can differentiate into neuron‐like cells after treatment with either nerve growth factor (NGF) or transduction with a retrovirus which expresses the K‐ras oncogene. The concomitant treatment of NGF plus ras differentiates PC12 cells further than either agent alone with respect to neurite outgrowth, acetylcholinesterase levels, and most strikingly, the number of synaptic vesicle (SV) clusters. These SV clusters in PC12 cell neurites closely resemble those in the presynaptic terminals of neurons. Such SV clusters have not been described in cell lines previously. The SV clusters from all three differentiated groups (NGF, ras, and NGF plus ras) were similar in size, shape, and configuration, except that the ones in the doubly treated group occur in higher frequency and have more vesicles. The synaptic nature of these vesicle clusters was demonstrated by their regulated depletion after potassium stimulation. Furthermore, these vesicle clusters stained positively for two SV‐associated proteins, synapsin I and synaptophysin, by EM immunocytochemistry (ICC). Such SV clusters in a cell line are very useful for characterizing the regulated release of SVs and the distribution of SV‐related antigens in intact cells. Analysis by SDS‐gel electrophoresis and immunoblotting indicated that synapsin I levels are higher in all three differentiated groups compared to untreated cells; whereas synaptophysin levels are lower in cells exposed to NGF alone or with NGF and ras double treatment. Possible convergence and/or divergence on the mechanisms of NGF and ras differentiation in PC12 cells are discussed. © 1995 Wiley‐Liss, Inc.

This article is a US Government work and, as such, is in the public domain in the United States of America.
Response of olfactory Schwann cells to intranasal zinc sulfate irrigation
Authors: Chuah M. I. , Tennent R. , Jacobs I.
Published: January 2005

The response of olfactory Schwann cells was assessed at 2, 4, and 7 days following intranasal zinc sulfate irrigation in 1‐month‐old mice. Ultrastructural and immunohistochemical observations showed dramatic differences between experimental and control mice which had been washed with saline intranasally. Two days after zinc sulfate treatment, many olfactory nerve bundles contained patchy areas of axonal degeneration, while the cell bodies of the olfactory Schwann cells appeared to have increased in electron density and to have shifted peripherally. Some of the cell bodies protruded from the surface of the axon fascicle, suggesting that the olfactory Schwann cells were in the initial process of migrating away. On the fourth day when most of the olfactory axons had degenerated, some olfactory Schwann cells were aligned immediately beneath the basal lamina of the olfactory epithelium. These cells were immunopositive for the S‐100 protein and possessed an expanded perinuclear space. Many olfactory Schwann cells were present in the region beneath the cribriform plate, while some appeared to have passed through the gaps between the bony plates to reach the olfactory bulb. Hence, the results showed that many olfactory Schwann cells migrated towards the olfactory bulb following loss of axonal contact. Furthermore, on the seventh day following zinc sulfate treatment, some olfactory Schwann cells in the vicinity of the olfactory bulb appeared phagocytic, as indicated by their extension of processes around fragments of cell debris and the presence of lysosome‐like organelles in the perikaryon. The control mice which had been intranasally irrigated with saline did not demonstrate massive olfactory axonal degeneration, and the morphology of the nasal cavity region was similar to that of normal mice. © 1995 Wiley‐Liss, Inc.
Selective block of Ca2+‐dependent K+ current in crayfish neuromuscular system and chromaffin cells by sea anemone Bunodosoma cangicum venom
Authors: Araque A. , Urbano F. J. , Cerveñansky C. , Gandía L. , Buño W.
Published: January 2005

The effects of the nematocyst venom of the sea anemone Bunodosoma cangicum on depolarization‐activated currents were studied in opener crayfish muscle fibers and in cultured bovine chromaffin cells. The venom selectively and reversibly blocked the Ca2+ ‐dependent K+ current (IK(Ca)) present in crayfish muscle in a dose‐dependent manner without affecting voltage‐gated Ca2+ or K+ currents. Furthermore, the venom also reduced IK(Ca) in chromaffin cells, without modifying voltage‐gated Na+, Ca2+, or K+ currents. Synaptic transmission in crayfish muscle was also affected by the venom. Repetitive excitatory and inhibitory postsynaptic currents (each associated with a presynaptic action potential) were evoked by each nerve stimulus, suggesting that presynaptic IK(Ca) may control the electrical activity of excitatory and inhibitory presynaptic fibers. We conclude that B. cangicum venom includes a toxin that selectively and reversibly blocks Ca2+ ‐dependent K+ currents in crayfish muscle and in bovine chromaffin cells, and modifies excitatory and inhibitory synaptic transmission, probably abolishing a similar conductance at the presynaptic fibers. © 1995 Wiley‐Liss, Inc.
Seed reserves of chickpea in relation to molybdenum supply
Authors: Nautiyal Nirmala , Singh Soni , Chatterjee Chitralekha
Published: January 2005

Chickpea (Cicer arietinum L), cv K75 plants were grown till maturity at 0.00001, 0.0001, 0.001 (deficient), 0.02 (adequate), 0.2 (supranormal) and 2.0 (excess) mg dm−3 Mo in refined sand. The pod and seed yield of chickpea were at a maximum at 0.2 mg dm−3 Mo, which is ten times higher than the usual Mo requirement. The seed weight of chickpea was decreased more by low (<0.02 mg dm−3) than excess (2 mg dm−3) Mo. In chickpea seeds, the concentrations of starch, reducing, non‐reducing and total sugars were highest at 0.02 mg dm−3 Mo and decreased by Mo stress (<>0.02–0.2 mg dm−3). In comparison, the content of methionine, lysine, legumin, vicilin, total proteins, protein and non‐protein nitrogen in seeds of chickpea decreased variably both at low (<0.02 mg dm−3) and high (>0.2 mg dm−3) Mo. Both deficiency and excess of Mo deteriorated the quality of seeds by increasing the content of phenols, cysteine and albumin and decreasing that of methionine, lysine, legumin and vicilin protein fractions, apart from reducing the seed weight. The quality of seeds deteriorated more by deficiency than excess of Mo in chickpea. Copyright © 2004 Society of Chemical Industry
Parkinsonism following dystonia in three patients
Authors: Katchen Marc , Duvoisin Roger C.
Published: January 2005

Three patients who presented initially with dystonia and subsequently developed typical idiopathic parkinsonism were evaluated: One patient presented with a writer's cramp, one with axial dystonia, and one with Meige syndrome. All three displayed amelioration of their dystonia with progression of their parkinsonism over a period of 2 to 15 years. Treatment with levodopa gave some relief of the parkinsonism symptoms in two patients but exacerbated or reactivated the dystonia. It is suggested that both the dystonia and the parkinsonism represent the changing clinical expression of the same disorder at different times in its evolution.
Sudden onset of confusion with severe exacerbation of parkinsonism during levodopa therapy
Authors: Sage Jacob I. , Duvoisin Roger C.
Published: January 2005

Two patients with Parkinson's disease presented with unprovoked, abrupt onset of hallucinations, confusion and the simultaneous worsening of parkinsonian symptoms. This clinical syndrome appears to be a rare complication of dopaminergic therapy since improvement occurred gradually with reduction of Sinemet dosage.
Acetazolamide responsive hereditary paroxysmal ataxia
Authors: Friedman J. H. , Hollmann P. A.
Published: January 2005

The fourteenth family with an apparently autosomal dominant paroxysmal ataxia is described. As in the seven families described since 1978, acetazolamide completely cured the attacks. A possible mechanism of action of acetazolamide is discussed.
Adrenergic beta2‐selective blocker in isoprenaline‐enhanced essential tremor
Authors: Teräväinen Heikki , Huttunen Juha
Published: January 2005

A beta2‐selective adrenergic‐receptor‐blocking drug, ICI 118.551,150 mg/day, prevented almost as effectively as the nonselective antagonist propranolol, 240 mg/day, the isoprenaline enhancement of essential tremor amplitude.
Continous intracerebroventricular infusion of dopamine and dopamine agonists through a totally implanted drug delivery system in animal models of Parkinson's disease
Authors: De Yebenes J. G. , Fahn S. , Lovelle S. , Jackson‐Lewis V. , Jorge P. , Mena M. A. , Reiriz J. , Bustos J. C. , Magariños C. , Martinez A.
Published: January 2005

We studied the effect of intracerebroventricular infusion of dopamine and dopamine agonists in rat and primate models of Parkinson's disease as an experimental approach to the treatment of levodopa‐induced fluctuations. The infusion of dopamine, lisuride, and pergolide into the ventricle ipsilateral to the lesion, by 6‐hydroxydopamine, of the nigrostriatal pathway induced a contralateral rotation which was maximal 24–48 h after infusion and whose intensity progressively decreased over the period of 1 weak. [3H] Spiperone binding was decreased by the infusion of dopamine but the responses to subcutaneous apomomorphines were unchanged. The infusion of dopamine also restored the levels of monoamines in the rat brain. In chronic reserpized rats, the infusion of dopamine restored brain levels of dopamine but did not reverse akinesia unless monoamine oxidase inhibitors were simultaneously administered, either systemically or intracerebroventricularly. Lisuride and pergolide proved much weaker than dopamine in reversing the effects of reserpine. Intracerebroventricular infusion of dopamine plus deprenyl reversed MPTP induced akinesia in monkeys but the pump used for the delivery was not well tolerated, because of its size, by the animals.
Parkisonism induced by high‐dose cytosine arabinoside
Authors: Luque F. Antonio , Selhorst John B. , Petruska Paul
Published: January 2005

We report a severe parkinsonian condition following high dose, parenteral cytosine arabinoside (Cytosar) that persisted for 8 weeks. The durg was used in a patient with acute myelogenous leukemia that was refractory to all other treatment. The syndrome was partially responsive to antiparkinsonian durgs and fortunately remitted completely within 12 weeks.
Dystonia and tremor following exposure to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin
Authors: Klawans Harold L.
Published: January 2005

Forty‐seven railroad workers who were exposed to polychlorinated phenols, including dioxin (TCDD), during 1979 while cleaning up the chemical spillage following damage to a tank car filled with these chemicals were followed medically for the subsequent 6 years. Two committed suicide. The initial neurological complaints included a sense of fatigue and muscle aching, both of which have been reported in other individuals following dioxin exposure. On detailed neurological examination in December, 1985, 24 of 45 had dystonic writer's cramp and/or other action dystonias of the hands. None of the involved individuals had a family history of dystonia, and all 24 dated the onset of the dystonia to the first 2 to 3 years subsequent to their toxic exposure. The dystonias varied in severity but were usually mild. No other types of dystonic involvement were recognized. Thirty‐five of the 45 individuals also manifested postural and terminal intention tremor which resembled benign essential tremor. None of the involved individuals had a family history of tremor, and all 35 of those affected dated the onset of the tremor to some time subsequent to their toxic exposure. Forty‐three of 45 patients had histories and findings suggestive of peripheral neuropathy. This is the first report relating and type of dystonia to prior dioxin exposure and the first report relating action dystonia, such as dystonic writer's cramp, and postural/terminal intention tremor, to toxic exposure of any type.
Blink reflex studies in focal dystonias: Enhanced excitability of brainstem interneurons in cranial dystonia and spasmodic torticollis
Authors: Tolosa Eduardo , Montserrat Luis , Bayes Angeles
Published: January 2005

We have studied the orbicularis oculi reflex to paired stimuli in patients with various forms of focal dystonia and in normal controls. In normals, the conditioning stimulus (CS) facilitated the test stimulus (TS) early response (R1), but markedly inhibited the TS polysynaptic late response (R2). In all types of dystonias studied the CS facilitated the TSR1 as in normals. However, in patients with blepharospasm (alone or associated with oromandibular dystonia), spasmodic torticollis, or spasmodic dysphonia, it inhibited the TSR2 significantly less than that of the controls, with marked enhancement of the recovery curve of the late response. The TSR2 recovery curve of patients with focal arm dystonia was normal. These results are indicative of increased brainstem interneuron excitability in the various dystonias mediated by the cranial nerves, but not in focal arm dystonias such as dystonic writer's cramp. This abnormality might be caused by an abnormal input possibly from the basal ganglia upon these brainstem cells. Our results also suggest that a similar pathophysiology underlies the various focal dystonias of the head and neck.
Isoniazid therapy in Parkinson's disease
Authors: Gershanik O. S. , Luquin M. R. , Scipioni O. , Obeso J. A.
Published: January 2005

The effect of isoniazid on levodopa‐induced dyskinesias has been evaluated in 20 patients with Parkinson's disease, following a serendipitous observation that choreic dyskinesias induced by levodopa in one parkinsonian patient were markedly reduced during treatment with isoniazid for tuberculous infection. A mean average isoniazid dose of 290 mg was given without any change in current antiparkinsonian treatment. “Benefit of dose” choreic dyskinesias were markedly reduced in 18 patients within the first few weeks of treatment. This effect was accompanied by an intolerable worsening of parkinsonian signs. All patients returned to their basal situation after isoniazid interferes with the therapeutic action of levodopa and dopamine agonists. The precise mechanism by which this action occurred is not known, but several possible explanations are discussed.
Delayed‐onset dystonia associated with corticospinal tract dysfunction
Authors: Factor Stewart A. , Sanchez‐Ramos Juan , Weiner William J.
Published: January 2005

We report a young man with delayed‐onset dystonia secondary to a cerebral infarction. The infarction was caused by an embolic event at the age of 18 months. Delay to onset of dystonia was 16 years and, prior to the onset of dystonia, the patient had profound corticospinal tract dysfunction manifested by a severe hemiparesis. Computed tomography scan revealed infarction of the lentiform nucleus and precentral gyrus. The profound involvement of the corticospinal tract both clinically and radiologically are features not previously described in symptomatic dystonia and contradict the concept that sparing of the corticospinal tract is an essential feature for the onset of acquired dystonia.
Dementia and treatment with L‐dopa in Parkinson's disease
Authors: Hietanen M. , Teräväinen H.
Published: January 2005

We compared the neuropsychological performance of patients with Parkinson's disease who were young at onset of the disease (mean age, 41.4 years) and had received prolonged L‐dopa treatment (mean, 52.1 months) with nontreated patients of the same age. A similar comparison was made for patients who were older at onset of the disease (mean, 62.1 years). There were no significant differences in cognitive and memory functions between the L‐Dopa‐treated and untreated young patients, whereas the L‐Dopa‐treated patients in the older age group performed more poorly than untreated patients in some memory tests (Wechsler Memory Scale I: logical and visula) and cognitive functions (Wechsler Adult Intelligence Scale: similarities, block design, and cognitive flexibility). Treatment duration, disease duration, and mean L‐Dopa dose were comparable for the two age groups. After linear effects of age and disease duration had been eliminated, the duration of L‐Dopa treatment did not correlate with the cognitive vaiables studied. These observations suggest that treatment with L‐Dopa may not be the cause of cognitive impairment in Parkinson's disease.
Primary CNS lymphoma presenting as a choreic movement disorder followed by segmental dystonia
Authors: Poewe W. H. , Kleedorfer B. , Willeit J. , Gerstenbrand F.
Published: January 2005

Clinical presentation of primary CNS lymphoma with an extrapyramidal movement disorder has not been recorded. A 66‐year‐old woman presented with chorea involving her left arm and subsequently developed rightsided segmental dystonia with prominent hemifacial dystonic spasms, milder torticollis and dystonia of the right arm. Investigations revealed primary CNS lymphoma with extensive involvement of the right‐sided basal ganglia as well as lesions confined to the head of the left caudate nucleus and the corpus callosum. Chorea of her left arm subsided with progressing disease while remission of right‐sided segmental dystonia was observed following radiotherapy of the brain. This patient's findings and a review of the literature suggest a possible relation between cranio‐cervical dystonia and pathology affecting the head of the caudate nucleus.
Degenerative cerebellar ataxia and focal dystonia
Authors: Fletcher N. A. , Stell R. , Harding A. E. , Marsden C. D.
Published: January 2005

Eight patients with a variety of degenerative cerebellar ataxias are described in whom focal dystonia was a prominent presenting feature.
Oxyferriscorbone elevates the total iron content of blood but not brain
Authors: Dexter D. T. , Jenner P. , Marsden C. D.
Published: January 2005

Following the intravenous infusion of oxyferriscorbone into the tail vein of the rat, the blood and brain metal ion content was measured over the following 72 h period. Administration of oxyferriscorbone increased the total iron content of blood for up to 24 h following intravenous infusion. In contrast, there was no increase in the total iron content of the cerebellum or striatum. Overall, there was no change in total zinc or copper content of the blood or brain following oxyferriscorbone administration. The effect of oxyferriscorbone in Parkinson's disease may not be related to any alteration in total iron content of the brain.
Effects of etybenzatropine and diazepam on levodopa‐induced diphasic dyskinesias in Parkinson's disease
Authors: Pourcher Emmanuelle , Bonnet Anne‐Marie , Kefalos John , Dubois Bruno , Agid Yves
Published: January 2005

Levodopa‐induced onset and end‐of‐dose dyskinesia are rare but disabling disorders. Although they can be attenuated by increasing and dividing the daily dose of levodopa, this does not constitute a therapeutic approach. In this pilot study, etybenzatropine, an anticholinergic drug, and diazepam, a selective benzodiazepine, were administered in addition to a single dose of levodopa in nine patients with Parkinson's disease. Both drugs tended to decrease the severity and the duration of onset and end‐of‐dose dyskinesia, and to increase the duration of action of levodopa on parkinsonian symptoms.
Treatment of movement disorders with trihexyphenidyl
Authors: Jabbari Bahman , Scherokman Barbara , Gunderson Carl H. , Rosenberg Michael L. , Miller Joseph
Published: January 2005

The clinical efficacy of the trihexyphenidyl was investigated in 100 patients with movement disorders. The study group consisted of 54 women and 46 men. Their ages ranged from 18 to 70 years, and their duration of illness varied from a few months to 36 years. Each patient had a videotape of the movements and a neurological examination, before administration of the drug, at the time of maximum or effective dosage, and one week after withdrawal from trihexyphenidyl. The drug was administered at an initial total daily dose of 2 mg and gradually increased to a total daily dose of 60 mg over a period of 4–6 weeks. Improvements were rated both clinically and from the videotapes. Three groups of movement disorders demonstrated a significant response to trihexyphenidyl: (1) dystonia 37%; tonic torticollis demonstrated a significantly better response than the clonic variant (80% vs. 22%). (2) rhythmic‐oscillatory movements of brainstem–cerebellar origin (palatal myoclonus, pendular nystagmus, facial myokymia) 90%; (3) cerebellar tremor 75%. Among 32 responders, 17 (56%) continued taking trihexyphenidyl beyond 24 months. Side effects consisted of dryness of the mouth, jitteriness, stomatitis, blurred vision, and forgetfulness.
Cerebral sarcoidosis presenting as supranuclear gaze palsy with hypokinetic rigid syndrome
Authors: Schlegel U. , Clarenbach P. , Cordt Almut , Steudel A.
Published: January 2005

A 31‐year‐old man with histologically documented pulmonary sarcoidosis developed a severe hypokinetic rigid syndrome with a supranuclear gaze palsy following recurrent lymphocytic meningitis and occlusive hydrocephalus. Magnetic resonance imaging (MRI) showed multiple hyperintense foci in the CNS, not detectable by computed tomography (CT). Long‐term steroid therapy led to clinical complete remission.
A case of rabies in North America
Authors: Bhatt Mohit , Wolters Erik , Tsui Joseph , Snow Barry J. , Calne Donald B.
Published: January 2005

A 25‐year‐old man developed classical hydrophobic rabies 3 months after being bitten on the face. We present his involuntary movements on videotape and discuss the clinical and epidemiological features of rabies. Though rabies is seen in tropical countries commonly and in North America occasionally, recording of the clinical features is rare.