bluuebunny/crossref_metadata_2025 huggingface dataset:
Localization and partial characterization of a 60 kDa citrulline‐containing transport form of myelin basic protein from MO3‐13 cells and human white matter
Authors: Ursell M. R. M. , McLaurin J. , Wood D. D. , Ackerley C. A. , Moscarello M. A. , Russell J. T.
Published: January 2005

The localization of myelin basic proteins (MBPs) in an immortalized human‐human hybrid cell line (MO3‐13) formed by fusion of rhabdomyosarcoma TE671‐TG6 with primary human oligodendrocytes, cultured from surgical specimens, demonstrated an intracellular localization in vesicles and vacuoles with an intricate internal membranous network and to the external surface of the cell by immunogold electron microscopy. The availability of antibodies to one of the components of MBP, i.e., the citrulline containing component (“C‐b”), permitted us to localize this component of MBP to intracellular vacuoles and also on the external surface of the MO3‐13 cells. Since the apposition of the external surfaces of the oligodendrocyte is responsible for the intraperiod line of the myelin sheath, localization of C‐8 to the external surface of non‐permeabilized cells by immunogold scanning electron microscopy is consistent with our observations that C‐8 is localized to the intraperiod line of myelin (McLaurin et al.: J Neurosci Res 35:618‐628, 1993).

Western blots of isolated MBP from MO3‐13 cells, probed with an antibody reactive with residues 130‐137 of MBP, recognized a protein in the 60 kDa range. No immunoreactivity was found in the 18.5 kDa range. This 60 kDa protein also reacted with a monoclonal antibody raised with residues 70‐84 of MBP, 2 different polyclonals raised with whole bovine MBP, an antibody to human MBP raised in monkeys, and the anti‐citrulline antibody. These data strongly suggested that the 60 kDa protein contained MBP sequences within its primary structure. A similar protein has been isolated from human myelincontaining fractions but not from compact myelin demonstrating that the 60 kDa protein from MO3‐13 cells was not an artefact related to fusion. Sequence determination of peptides obtained from enzymic and chemical cleavages revealed that the 60 kDa protein contained MBP sequences and peptides with 55‐60% homology with dynamin, a protein involved in intracellular transport. These data suggest that the externalization of MBP in this cell involves transport by fusion of MBP with another protein. By sequestering MBP in a larger protein, the possibility of inducing autoimmune disease by MBP released, due to cell death, is minimized. © 1995 Wiley‐Liss, Inc.
Control of neuronal morphology in vitro: Interplay between adhesive substrate forces and molecular instruction
Authors: Lochter A. , Taylor J. , Braunewell K.‐H. , Holm J. , Schachner M.
Published: January 2005

Among the factors which influence neuronal morphology, the degree of substrate adhesivity has been suggested to play an important role in the growth and guidance of neurites. The present study was undertaken to investigate apparently contradictory results relating substrate adhesivity to the extent of neurite outgrowth. By using substrates coated with different concentrations of polyornithine to vary adhesivity, we could show that intermediate levels of neuron‐to‐substrate adhesive strength favored neurite outgrowth more than substrates of high or low adhesivity. However, when neurons were plated on substrates derived from the extracellular matrix, the strength of neuronto‐substrate adhesion was important for the growth of dendrite‐like minor neurites, but not for the extension of axon‐like major neurites, which grew independently of adhesive forces. On substrates of the cell adhesion molecule L1, growth of both major and minor neurites was adhesion‐independent. Finally, in the presence of tenascin added to the culture medium, neurite growth was inhibited irrespective of the adhesivity of the substrate and the presence of substrate‐bound extracellular matrix molecules or L1. These observations suggest that intermediate forces of adhesivity favor neurite growth in general, but that purely adhesive forces can be dominated by specific molecular instructions which differentially affect growth of major and minor neurites in positive and negative ways. © 1995 Wiley‐Liss, Inc.
Hierarchical analysis of the nerve growth factor‐dependent and nerve growth factor‐independent differentiation signaling pathways in PC12 cells with protein kinase inhibitors
Authors: Campbell X. Z. , Neet K. E.
Published: January 2005

The effects of a series of protein kinase inhibitors on nerve growth factor (NGF)‐dependent and NGF‐independent neurite outgrowth in PC12 cells have established an ordered relationship among those protein kinases sensitive to down regulation by bryostatin, stimulation by staurosporine, inhibition by sphingosine, or inhibition by 6‐thioguanine (6‐TG). Quantitation of the biphasic staurosporin effects on NGF‐induced neurite outgrowth (Hashimoto and Hagino: J Neurochem 53:1675‐1685, 1989) gave an IC50 of 2‐4 nM for inhibition and an EC50 of 15‐20 nM for induction of neurite extension. Both sphingosine and 6‐TG inhibited neurite outgrowth induced by staurosporine and basic fibroblast derived growth factor (bFGF), as well as by NGF; therefore, sphingosine‐ and 6‐TG‐sensitive protein kinase steps occur after the convergence of the NGF, bFGF, and staurosporine signal pathways. Down regulation of protein kinase C by bryostatin chronic treatment, which inhibits NGF‐ and bFGF‐induced neuritogenesis (Singh et al.: Biochemistry 33:542‐551, 1994), did not inhibit the staurosporine‐induced neurite outgrowth. Thus, the bryostatin‐sensitive protein kinase C must occur subsequent to the convergence of the bFGF and NGF pathways, but before (or parallel to) staurosporine initiation of neurite outgrowth. In contrast, low concentrations of phorbol myristoyl acetate (PMA) or bryostatin, which activate protein kinase C activity, enhanced the staurosporine‐ or NGF‐induced neurite extension. These data indicate that stimulation of one or more protein kinase C isozymes can synergistically interact with the signaling pathway to increase the rate of neuritogenesis. Inhibition by 5‐7.5 nM staurosporine acted rapidly to arrest and decrease development of neurites up to 24 hr after NGF treatment, as did K252a and NGF ployclonal antibody addition. Our cellular data support the concept that staurosporine acts to inhibit the NGF receptor Trk (Nye et al.: Mol Biol Cell 3:677‐686, 1992), but that downstream steps can be activated by the higher concentration of staurosporine to bypass Trk and lead to neurite generation. Effects of staurosporine, 6‐TG, and sphingosine on c‐fos gene induction with or without NGF were not correlated with the generation of neurites. The sequence of protein kinases sensitive to these effectors appears to be in the order (but not consecutive) bryostatin, staurosporine, sphingosine, and 6‐TG. © 1995 Wiley‐Liss, Inc.
Radical formation site of cerebral complex I and Parkinson's disease
Authors: Fukushima T. , Tawara T. , Lsobe A. , Hojo N. , Shiwaku K. , Yamane Y.
Published: January 2005

Paraquat was reduced to the paraquat radical via complex I in bovine cerebral mitochondria and accelerated lipid peroxidation. Thirty‐kilodalton subunit of complex I was considered to be the radical formation site, because of its marked destruction by the paraquat radical. The lipid peroxidation by the paraquat radical was suppressed not only by superoxide dismutase (SOD) but also by mannitol. The destruction of complex I subunits via lipid peroxidation must have been caused by the hydroxyl radical which was formed from the superoxide radical. The same phenomenon was observed by using 1‐methylnicotinamide (MNA), which contains the same partial structure as paraquat in itself and is metabolized from nicotinamide in a living body. We observed NADH oxidation by MNA via cerebral complex I (Km = 26.3 mM), and MNA destroyed some complex I subunits, especially 30‐kilodalton protein. Paraquat might be useful for studying the pathogenesis of Parkinson's disease (PD) in vitro, and MNA is expected to be one of the causal substances of PD from the viewpoint of the oxidative stress theory. © 1995 Wiley‐Liss, Inc.
Coordinated upregulation of α1‐ and β11‐tubulin mRNAs during collateral axonal sprouting of central peptidergic neurons
Authors: Paden C. M. , Zhou X. , Watt J. A. , Burton R. , Pickett J. , Oblinger M. M.
Published: January 2005

An in situ hybridization study was performed to determine the relationship between levels of mRNAs for the axonal growth‐associated αl‐tubulin and βZII‐tubulin isotypes and the process of collateral axonal sprouting by identified central nervous system (CNS) neurons. A unilateral hypothalamic knife‐cut was used to hemisect the hypothalarnoneurohypophysial tract, which results in a robust collateral sprouting response by the uninjured neurons of the contralateral supraoptic nucleus (SON) (Watt and Paden: Exp Neurol 111:9‐24, 1991). At 10 and 30‐35 days after the lesion, cryosections of the SON were obtained and hybridized with 35S‐labeled cDNA probeses specific to αl‐ and β11‐tubulin mRNAs. Quantitative evaluation of the resulting autoradiographs revealed that αl‐tubulin mRNA levels were significantly increased by 10 days in SON neurons that were undergoing collateral sprouting compared to controls and that this increase was sustained at 30‐35 days post‐lesion. Less marked increases in hybridization intensity of the βII‐tubulin probe were also apparent in sprouting neurons at both 10 and 30‐35 days after the lesion, but were statistically significant only at 10 days. The measured increases in intensity of hybridization of αl‐ and β11‐tubulin probes are likely to be conservative estimates of the underlying increase in αl‐ and β11‐tubulin mRNA levels because sprouting SON neurons undergo significant hypertrophy. High levels of both αl‐ and βII‐tubulin mRNAs were also seen in surviving axotomized SON neurons ipsilateral to the hypothalamic lesion. We conclude that the pattern of regulation of αl‐ and β11‐tubulin mRNAs in CNS neurons which are capable of supporting new axonal growth includes three elements: maintenance of significant basal αl‐ and β11‐tubulin mRNA pools in mature neurons, rapid increases in the pool size of the mRNAs following stimulation of collateral sprouting, and sustained elevation of mRNA levels during the period of axonal sprouting. © 1995 Wiley‐Liss, Inc.
Spontaneous opening of the acetylcholine receptor channel in developing muscle cells from normal and dystrophic mice
Authors: Franco‐Obregón A. , Lansman J. B.
Published: January 2005

Single‐channel activity was recorded from cell‐attached patches on skeletal muscle cells isolated from wild‐type mice and from mice carrying the dy or mdx mutations. Spontaneous openings of the nicotinic acetylcholine receptor channel (nAChR) were detected in virtually all recordings from either dy/dy or dy/ + myotubes, but only infrequently from wild‐type or mdx myotubes. Spontaneous openings were also present in most recordings from undifferentiated myoblasts from all of the mouse strains studied. The biophysical properties of the spontaneous activity were similar to those of the embryonic form of the nAChR in the presence of acetylcholine (ACh). Examination of the single‐channel currents evoked by low concentrations of ACh showed a reduced sensitivity to the agonist in the dystrophic dy and mdx myotubes, but not in wild type myotubes. The results suggest that alterations in nAChR function are associated with the pathogenesis of muscular dystir ophy in the dy mouse. © 1995 Wiley‐Liss, Inc.
Regulation of protease nexin‐1 and angiotensin II receptor subtype 1 expression: Inverse relationship in experimental models of nerve injury
Authors: Bleuel A. , Monard D.
Published: January 2005

The up‐regulation of PN‐1 following nerve lesion has been investigated in vitro in cultures of dorsal root ganglion (DRG) explants, sciatic nerve segments, and isolated Schwann cells. In the first culture model, Schwann cells associated with neuronal processes synthesized small amounts of PN‐1. Injury of the neurites emerging from the DRGs led to enhanced levels of PN‐1 in Schwann cells located distal to the lesion site where degeneration of neuronal processes took place. In cultured sciatic nerve segments, PN‐1 synthesis increased with a time‐course comparable to that in ganglion explants following lesion. In the third model, PN‐1 levels gradually rose in isolated Schwann cells during the first 3‐8 days in culture. Dissociation of Schwann cells from the sciatic nerve therefore causes an effect similar to nerve damage. Impairment of Schwann cell‐neuron interactions was followed by a reduction in the expression levels of the angiotensin II (Ang II) receptor subtype AT1 in all three systems studied. Since the neuropeptide Ang II is able to repress PN‐1 synthesis in cultured Schwann cells, loss of neuronal contact might decrease their responsiveness to Ang II, thus resulting in PN‐1 upregulation by default. © 1995 Wiley‐Liss, Inc.
Laminin overrides the inhibitory effects of peripheral nervous system and central nervous system myelin‐derived inhibitors of neurite growth
Authors: David S. , Braun P. E. , Jackson D. L. , Kottis V. , McKerracher L.
Published: January 2005

Axon growth inhibitory proteins associated with central nervous system (CNS) myelin are responsible in part for the absence of long distance axon regeneration in the adult mammalian CNS. We have recently reported that myelin‐associated glycoprotein (MAG), which is also present in peripheral nerves, is a potent inhibitor of neurite growth. This was surprising given the robust regenerative capacity of peripheral nerves. We now provide evidence that myelin purified from peripheral nerve also has neurite growth inhibitory activity. However, this activity can be masked by laminin, which is a constituent of the Schwann cell basal lamina. We also report that laminin, which is largely absent from the normal adult mammalian CNS, when added to purified CNS myelin, can override the neurite growth inhibitory activity in CNS myelin. These results have important implications for the development of strategies to foster axon regeneration in the adult mammalian CNS where multiple growth inhibitors exist. © 1995 Wiley‐Liss, Inc.
Relationship of lead‐induced proteins to stress response proteins in astroglial cells
Authors: Opanashuk L. A. , Finkelstein J. N.
Published: January 2005

Astroglial cells are resistant to cell death and morphologic damage following lead (Pb) exposure at concentrations which elicit detrimental effects in neurons. A possible explanation may be that astroglial cells respond to Pb by increasing the expression of specific proteins, such as heat‐shock proteins (HSPs), which confer resistance to low levels of Pb. However, there has been relatively limited information regarding the ability of Pb to evoke the synthesis of HSPs. In the current study, pulse‐labeling of cultured astroglial proteins with [3H]‐leucine was used to evaluate the nature of Pb‐induced changes in protein expression. The effect of Pb on newly synthesized proteins was compared to the response elicited by heat‐shock and oxidative injury. Immunoblot analysis was utilized to examine alterations in levels of various stress proteins including HSP27, HSP70, HSP90, and heme oxygenase‐1 (HO‐1). Even though Pb induced the synthesis of proteins with estimated molecular weights of 23 kDa, 32 kDa, 70 kDa, and 90 kDa, the accumulation of HSPs other than HO‐1 was not observed. Hyperthermia and treatment with Na arsenite both resulted in enhanced expression of HSP70 and HO‐1. In addition, exposure to hydrogen peroxide (H2O2), cadmium (Cd), and lipopolysaccharide (LPS) stimulated a rise in HO‐1 levels. Although cellular insult failed to elicit an increase in either HSP27 or HSP90, cultured astroglia expressed readily detectable levels of both these proteins. Furthermore, Pb exposure resulted in the development of crosstolerance to subsequent injury by treatment with either Cd or H2O2. The results of this study indicate that Pb triggers a less conventional stress response in astroglial cells, which may provide enhanced resistance to the toxic effects of Pb. © 1995 Wiley‐Liss, Inc.
S‐100 immunoreactivity in rat brain glial cultures is associated with both astrocytes and oligodendrocytes
Authors: Richter‐Landsberg C. , Heinrich M.
Published: January 2005

S‐100 protein, a Ca2+‐binding protein of the EFhand type, is most abundant in the brain, and is involved in cell differentiation and the molecular mechanisms underlying cytoskeletal organization. We have investigated the immunocytochemical localization of S‐100 protein in rat brain glial cultures prepared from the cerebral hemispheres of newborn rats. In mixed glial cultures, containing astrocytes type I and II and oligodendrocytes at various stages of differentiation, S‐100 immunoreactivity was detected in all three cell types. Double immunofluorescence analysis revealed that in astrocytes, S‐100 immunoreactivity was mainly colocalized with glial fibrillary acidic protein (GFAP), while in oligodendrocytes a close association with microtubular structures was observed.

For immunoblot analysis, highly enriched oligodendrocytes and astrocytes were separately cultured for another week, and their extracts were analyzed by immunoblotting. The immunoblots of the cell extracts of both cell types showed a single S‐100‐immunoreactive polypeptide with an apparent molecular weight of approximately 12,000 daltons.

Thus, the data presented here demonstrate that S‐100 protein is not confined to astrocytes but occurs also in oligodendrocytes of rat brain. The close association with the oligodendroglial cytoskeleton suggests that this protein could also play a regulatory role in the organization of microtubules in oligodendrocytes and hence may be involved in the formation and maintenance of the myelin‐containing membrane sheets. © 1995 Wiley‐Liss, Inc.
Neutrophilic defensins penetrate the blood‐brain barrier
Authors: Schluesener H. , Meyermann R.
Published: January 2005

Defensins are small, cationic, cyclic peptides that are abundantly stored in granules of neutrophils. Defensins non‐specifically interact with membranes by forming weakly ion‐selective pores. Here we demonstrate immunolocalization of defensin‐secreting cells in human brain. Defensins, secreted by activated granulocytes, apparently are not prevented by the blood‐brain barrier (BBB) from diffusing across cerebral endothelium to penetrate the neuropil for a considerable distance from the granulocyte. This is in contrast to other neutrophil proteins like the granuleassociated enzyme elastase or the cytosolic protein MRP‐14, which are strictly localized to the cytoplasm or granules of neutrophils. Thus, defensins, known chemokinetic and chemotactic molecules, display a unique distribution at BBB sites. © 1995 Wiley‐Liss, Inc.
Two mitogenic regions of myelin basic protein interact with different receptors to induce Schwann cell proliferation in a cAMP dependent process
Authors: Tzeng S.‐F. , Deibler G. E. , Neuberger T. J. , DeVries G. H.
Published: January 2005

Previous studies have shown that myelin basic protein (MBP) is mitogenic for Schwann cells (SCs) in the presence of elevated intracellular cAMP. Two mitogenic regions of MBP have been identified: one mitogenic region within the first 44 residues of the aminoterminus (1–44) and the other mitogenic region within the terminal 15 residues of the carboxyl end of the molecule (152–167). Unlike the mitogenic effect of a myelin enriched fraction (MEF), the mitogenic effect of MBP was not reduced by the addition of the lysosomal inhibitor, ammonium chloride. These data indicate that MBP causes SC proliferation by direct interaction of MBP with a surface receptor. Using Scatchard analysis of the binding of MBP to SCs, we report that treatment with forskolin does not cause the upregulation of receptors for MBP. Moreover, MBP blocks the cross‐linking of 125I‐bFGF with two fibroblast growth factor (FGF) receptors having apparent molecular weights of 140 kDa and 120 kDa, respectively. Since neither TGF‐β nor PDGFBB displaced cell surface bound 125I‐MBP, we conclude that MBP binds to the FGF receptor rather than other growth factor receptors. Furthermore, only MBP1–44 interacted with ganglioside GM1, whereas MBP152–167 did not interact with this ganglioside. These results are consistent with the view that ganglioside GM1 mediates the mitogenic effects of MBP1–44, while the FGF receptor mediates the mitogenic effect of MBP152–67. Intracellular cAMP of SCs was transiently increased after the addition of macrophage conditioned medium, suggesting that macrophages may produce factors in vivo which can transiently elevate intracellular cAMP levels, allowing a wave of SC proliferation in response to MBP‐related mitogens. ©1995 Wiley‐Liss, Inc.
On the mechanism of the inhibition of glutamine synthetase and creatine phosphokinase by methionine sulfoxide
Authors: Haghighi A. Zendedel , Maples K. R.
Published: January 2005

Beta amyloid peptides (Aβ), etiologically associated with Alzheimer's disease (AD), have been shown to inhibit both glutamine synthetase (GS) and creatine phosphokinase (CPK) in vitro. These two enzymes are affected in AD and are sensitive to oxidative stress. Residue 35 of the Aβ25‐35, the most potent section of the 40–42 amino acid long fragment of amyloid precursor protein (APP), is a methionine, which has been reported to be oxidized to methionine sulfoxide presumably via a free radical oxidation process. We questioned whether methionine sulfoxide would inhibit GS and CPK directly and if this inhibition also involved free radical oxidative stress. In this report, we demonstrate that methionine sulphoxide inhibits GS by about 50% and CPK by about 25% at 20 mM concentration. Neither intact SOD, nor ascorbate inhibit the action of methionine sulfoxide completely, with regard to the inactivation of GS. These results indicate that the action of methionine sulfoxide may not be directly due to the oxidation of GS by free radicals. In fact, the presence of exogenous proteins, such as denatured SOD or catalase, inhibit the action of methionine sulfoxide as, or more effectively than, the addition of active free radical antioxidant enzymes. © 1996 Wiley‐Liss, Inc.
Antigenotoxicity of extracts from Pleurotus citrinopileatus
Authors: Wang Jinn‐Chyi , Hu Shu‐Hui , Liang Zeng‐Chin , Lee Min‐Yen
Published: January 2005

While Pleurotus citrinopileatus is a widely used edible mushroom, little is known about its physiological effects. Extracts, including aqueous extract, water‐soluble polysaccharide (WSP), crude protein solution (CPS) and residue from chloroform–ethyl acetate–methanol elution (CEM), were obtained first from fruiting bodies, through a solid‐state culture, and then from the mycelium, through a submerged culture. This study explored the antigenotoxicity effects of these extracts from Pleurotus citrinopileatus via the Ames test and a spore rec‐Assay. The results showed that, regardless of where the extract came from, the fruiting body or the mycelium, the antigenotoxicity effect was highest for CEM, followed by CPS, aqueous extract and WSP. The results of the Ames test indicated that, among several mutagens, CEM had the highest inhibition rate against AFBl in TA98 and TA100 and the lowest inhibition rate against NQNO. The concentrations of the various extracts were as follows: water extracts were 1 mg ml−1 and 5 mg ml−1 WSP, while CPS and CEM were 0.4 mg ml−1 and 2 mg ml−1, respectively; the higher the concentration of the extract, the higher the antimutagenicity effect. The results of the rec‐Assay indicated that CEM had the highest anti‐DNA‐damaging activity with or without the S9 mixture; the higher the concentration, the more significant the effect (p < 0.05). The anti‐DNA‐damaging activities were lower in the water extract concentrations, at 30 µg disc−1 dry weight−1, while the WSP, CPS and CEM at 12, 150 and 60 µg disc−1, respectively, were high. Copyright © 2004 Society of Chemical Industry
Levodopa dose‐related fluctuations in presumed olivopontocerebellar atrophy
Authors: Lang A. E. , Birnbaum A. , Blair R. D. G. , Kierans C.
Published: January 2005

The parkinsonism that occurs in some patients with olivopontocerebellar atrophy (OPCA) can cause diagnostic confusion with idiopathic Parkinson's disease (IPD). The response to levodopa is usually a distinguishing feature, the OPCAs either failing to benefit or losing efficacy relatively quickly. A fluctuating response to levodopa in those OPCA patients who do benefit has not been emphasized in the literature previously. Reported here are three patients with presumed OPCA, dominated by parkinsonian features, who eventually developed typical fluctuations with morning akinesia, wearing off, and periodic lack of response related to meals. These fluctuations were a major source of disability and an important reason for diagnostic confusion with IPD. The possible mechanisms of these fluctuations are discussed.
Administration of MPTP to the common marmoset does not alter cortical cholinergic function
Authors: Garvey J. , Petersen M. , Waters C. M. , Rose S. P. , Hunt S. , Briggs R. , Jenner P. , Marsden C. D.
Published: January 2005

The administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) to common marmosets induced persistent motor deficits and decreased concentrations of dopamine, homovanillic acid, and 3,4‐dihydroxy‐phenylacetic acid (DOPAC) and [3H]dopamine uptake in the caudate‐putamen. There was an 80% reduction in tyrosine hydroxylase immunoreactive cells in substantia nigra. At 10 days following the start of MPTP administration, the activity of choline acetyltransferase in the thalamus and frontal cortex was unchanged compared with control animals. Similarly, specific [3H]QNB binding was unaltered. At 4–6 weeks following the start of MPTP treatment, choline acetyltransferase activity and [3H]QNB binding in the frontal cortex and thalamus remained unaffected. There was no evidence for cell loss in the nucleus basalis of Meynert or alteration in the intensity of staining for acetyl‐cholinesterase. MPTP treatment of the common marmoset produces a nigrostriatal lesion. In contrast, MPTP did not alter cortical cholinergic function and was not neurotoxic to the cholinergic cells in the nucleus basalis of Meynert.
Autosomal dominant episodic ataxia: A heterogeneous syndrome
Authors: Gancher Stephen T. , Nutt John G.
Published: January 2005

We describe six kindreds with autosomal dominant episodic ataxia, apparently representing three distinct syndromes. Four kindreds were characterized by episodic ataxia and response to acetazolamide, and in three, interictal nystagmus. One kindred was characterized by paroxysmal ataxia and in one member, paroxysmal choreoathetosis. The last kindred had brief attacks of ataxia and interictal neuromyotonia. The age of onset and severity of the disorder varied within each kindred. These kindreds illustrate the heterogenity of episodic ataxia as well as the variable expressivity within each kindred.
Focal asterixis caused by a small putaminal hemorrhage
Authors: Trejo José M. , Giménez‐Roldán Santiago , Esteban Angel
Published: January 2005

Unilateral asterixis and mild pure motor hemiparesis contralateral to a small putaminal hemorrhage were observed in a 74‐year‐old hypertensive man. The motor deficit proved to be rapidly reversible, but the focal asterixis remained for some time as the only sign of the intracranial hemorrhage. This case suggests that altered striopallidal inhibitory input to the thalamus probably disturbed the circuit subserving the maintenance of postural tone.
Long‐term follow‐up after stereotaxic basal ganglia surgery in Parkinsonism. A neuroanatomical study of a case showing unusual postural disorders
Authors: Viallet F. , Gambarelli D. , Alonzo B. , Sedan R. , Khalil R.
Published: January 2005

A 60‐year‐old man who had Parkinson's disease for 25 year became unable to maintain the upright position of the trunk while standing or walking. Because of a loss of postural fixation, his trunk sank forward until his back was horizontal. Fifteen years before, a bifocal implantation of radioactive yttrium‐90 had been performed by a stereotaxic procedure at the level of the globus pallidus (GP) and the ventrolateral thalamus, respectively on the right side. A second operation, 2 years later, had been made by electrocoagulation in the left ventrolateral thalamus. Postmortem examination showed the following features (a) neuronal cell loss in the pigmented nuclei of the brainstem with intracellular Lewy bodies and gliosis. These data corresponded with the usual pathology of idiopathic Parkinson's disease; (b) surgical lesions resulting from the previous stereotaxic operations in the right GP and the ventrolateral thalamus on both sides and (c) neuronal cell loss without gliosis in the right GP that was evident in regions spared by the surgical lesion. Moreover, these degenerative changes were particularly seen in the left GP, which was surgically unlesioned. The ansa lenticularis was demyelinated on both sides. These data might be consistent with a retrograde degenerative process affecting the pallidothalamic projections. Beside the role of the neuronal cell loss affecting the pars compacta of the substania nigra (SN) in akinesia, the role of the lesions affecting the G.P. in the genesis of postural disorders is suggested.
An investigation of the phenomenon of “set” in Parkinson's disease
Authors: Brown R. G. , Marsden C. D.
Published: January 2005

It has been suggested that patients with Parkinson's disease have a basic deficit in shifting “set.” Previous authors have used this hypothesis as an explanation for deficits on a range of cognitive tasks. An experiment was conducted to investigate this phenomenon. A reaction time paradigm was used in which the subject had to make left‐right decisions under two stimulus conditions. Both patients and controls showed a facilitation in performance with repetition within each blcok of trials, followed by a deterioration in performance when the stimulus type switched. Furthermore, the shapes of the reaction‐time functions were equivalent in both groups, suggesting that the patients had no deficit in either switching or establishing set in this task. In contrast, they were impaired on the Wisconsin Card Sorting Test. This dissociation suggests that patients with Parkinson's disease do not have a generalized deficit in switching set. It is suggested that patients with Parkinson's disease are impaired on tasks where they have to rely upon internal control for the regulation of behaviour, but are relatively unimpaired on tasks where external cues are available.
Crural and axial myoclonic dystonia following meralgia paraesthetica
Authors: Ter Bruggen J. P. , Tijssen C. C.
Published: January 2005

A 49‐year‐old man developed a syndrome of crural‐axial dystonia combined with segmental myoclonus 3 months after the onset of meralgia paraesthetica of the left leg. The association of this remarkable movement disorder with the pain syndrome is discussed.
Oculo‐facio‐skeletal myorhythmia as a cerebral complication of systemic Whipple's disease
Authors: Hausser‐Hauw Chantal , Roullet Etienne , Robert René , Marteau René
Published: January 2005

A fifth case of oculomasticatory myorthythmia associated with cerebral Whipple's disease is reported. This peculiar abnormal movement has never been described in association with cerebral dysfunction other than Whipple's disease. The present case exhibited rhythmic convergence of the eyes and synchronous (1–2 Hz) contractions of the masticatory muscles and of the proximal and distal skeletal muscles. These abnormal movements occurred 13 years after the beginning of the disease. They were persistent and unchanged until the death of the patient 3 months later. No treatment was effective to suppress the involuntary movements (clonazepam, baclofen, antibiotics). Associated neurological signs included global supranuclear ophthalmoplegia, facial weakness, bilateral ptosis, absent gag reflex, and intellectual deterioration.
Pathological report of four patients presenting with cranial dystonias
Authors: Gibb W. R. G. , Lees A. J. , Marsden C. D.
Published: January 2005

Secondary dystonias and experimental models of dystonia suggest that mechanisms responsible for primary dystonias may lie in the basal gaglia or brainstem. A histological study ahs been done in three patients with cranial dystonia (blepharospasm with oromandibular dystonia in two, blepharospasm alone in one), and one patient with craniocervical dystonia (oromandibular dystonia with retrocollis). In the patient with blepharospasm alone, an angioma, 0.5 mm in diameter, was found in the dorsal pons at the site of the central tegmental tract, confirming that some patients presenting with primary dystonias may have longstanding lesions in the brainstem. In the three other cases, the striatum, pallidum, thalamus, and brainstem were examined and cell populations in the putamen, substantia nigra, and inferior olives were compared with age‐matched controls, but no significant abnormality was found.
Genetic prediction in Huntington's disease: What are the limitations imposed by pedigree structure
Authors: Misra V. Peter , Baraitser Michael , Harding A. E.
Published: January 2005

The major factor limiting use of the polymorphic DNA sequence D4S10, genetically linked to the Huntington's desease (HD) locus, in clinical practice is the fragmented nature of HD families. A population survey in South Wales suggested that genetic prediction would only be possible in 15% of adults at risk as a result of this. We have analysed pedigrees from 151 families, containing 482 adults between 18 and 45 years of age who were at high risk of developing HD, 157 of whom had attended genetic counselling clinics. Thirtyseven percent of adults at high rist in these kindreds had the appropriate pedigree structure needed for presymptomatic testing. It should be possible to perform fetal exclusion tests in about 80% of pregnancies at risk.
Concurrent hypnogenic and reflex paroxysmal dystonia
Authors: Lehkuniec Estela , Micheli Federico , De Arbeliaz Roberto , Torres Marta , Paradiso Guillermo
Published: January 2005

A 29‐year‐old patient with nocturnal episodes of paroxysmal dystonia is described. In addition, attacks could be provoked by stimulation of his right foot. Treatment with phenytoin resulted in a marked reduction in the frequency of the episodes.
Neurochemical findings in neuroacanthocytosis
Authors: de Yebenes J. G. , Brin M. F. , Mena M. A. , De Felipe C. , del Rio R. M. , Bazan E. , Martinez A. , Fahn S. , Del Rio J. , Vazquez A. , de Seijas E. Varela
Published: January 2005

We performed a neurochemical study of the brain of two unrelated patients, living in different continents, with neuroacanthocytosis. The levels of monoamines and their metabolites, γ‐aminobutyric acid and substance P, were measured in several brain areas and the monoamine metabolites in cerebrospinal fluid. The binding of 3H‐spiperone to striatal membranes and to lymphoctytes was also measured. Both patients had a progressive neurological disorder with onset in the third decade of life and characterized by a complex movement disorder, epilepsy, muscular wasting, and changes in behavior. The movement disorder, epilepsy, muscular wasting, and changes in behavior. The movement disorder initially manifested with oromandibular dystonai and limb chorea, but at the time of death was characterized by a severe dystonic syndrome. The chemical changes were similar in the two patients. The most important neurochemical findings were a depletion of dopamine and its metabolites in most brain areas, most notably in the striatum, and elevation of norepiephrine levels in the putamen and globus pallidus. Substance P was markedly reduced in the striatum and substantia nigra. Our findings may provide clues to the neurochemical mechanisms underlying dystonia.
Multiple sclerosis presenting as adult onset dystonia
Authors: Coleman R. J. , Quinn N. P. , Marsden C. D.
Published: January 2005

Two patients are described in whom dystonia was the presenting feature of multiple sclerosis.
Off‐period belching due to a reversible disturbance of oesophageal motility in Parkinso's disease and its treatment with apomorphine
Authors: Kempster P. A. , Lees A. J. , Crichton P. , Frankel J. P. , Shorvon P.
Published: January 2005

Two L‐dopa‐treated patients with Parkinson's disease who developed distressing belching during “off” periods are reported. In each case, contrast cine radiography revealed disturbed oesophageal motility which disappeared after injection of the dopamine receptor agonist apomorphine. It is suggested that central dopaminergic abnormalities may be important in the aetiology of “off period belching”.
The use of glutethimide for treatment of essential tremor
Authors: McDowell Fletcher H.
Published: January 2005

Two patients with long‐standing intention tremor that was interfering with their ability to maintain employment were treated with glutethimide. In both patients, this agent successfully supressed tremor at doses of 1,000 mg and 4,000 mg per day. Glutethimide has been taken for as long as 14 years in one patient without evidence of side effects.
Choreoathetosis induced by cyproheptadine
Authors: Samie Mohammad Reza , Ashton Adam Keller
Published: January 2005

Cyproheptadine is an antihistamine with antiserotoninergic and anticholinergic properties. It is a relatively safe drug with many varied indications for usage, which rarely produces serious adverse neurologic sequelae. Reports of involuntary movement disorder secondary to cyproheptadine are rare. We present the case of a 17‐year‐old overdose victim which may be the first documented instance of cyproheptadine intoxication resulting in choreoathetosis. This hyperkinesia was most likely resultant from the anticholinergic properties of cyproheptadine. Although the choreoathetoid movement resolved spontaneously, the delirious state disappeared after administration of physostigmine.
Homolateral disappearance of essential tremor after cerebellar stroke
Authors: Dupuis M. J. M. , Delwaide P. J. , Boucquey D. , Gonsette R. E.
Published: January 2005

The case of a patient with essential tremor in whom tremor disappeared on the right side after a homolateral cerebellar infarct is reported. The pathophysiology of essential tremor remains unknown. Vascular and surgical lesions of dentorubrothalamic pathway have been reported to improve various kinds of tremor including essential tremor. In this patient, a lesion of this pathway related to the cerebellar infarct probably explains the homolateral cessation of essential tremor.
The sz mutant hamster: A genetic model of epilepsy or of paroxysmal dystonia?
Authors: Löscher Wolfgang , Fisher J. Edward , Schmidt Dieter , Fredow Gabriele , Hönack Dagmar , Iturrian W. B.
Published: January 2005

Attacks of sustained dystonic postures of limbs and trunk can be initiated by mild environmental stimuli in an inbred line of Syrian hamsters. The trait is determined by an autosomal simple recessive genetic mutation, originally designated by the gene symbol sz, because the abnormal movements were thought to represent epileptic seizures. The attacks, which can be reproducibly initiated by placing the sz mutant hamsters in a new environment, begin with rapid twitches of the vibrissae, flattened ears, and flattened posture of the trunk while walking, followed by facial contortions, rearing, and sustained posturing of trunk and limbs, often resulting in falling over to the side or backwards. In the final stage, the hamsters became immobile, which can last for hours. An increased tone of limbs and trunk muscles can be palpated during the attack. Electromyographical recordings in awake, unrestrained mutant hamsters showed that the onset of the attack coincided with continuous tonic muscle activity and phasic bursts, which were present even when the animals did not move. During the attack, the animals continue to react to external stimuli. Bilateral electroencephalographic (EEG) recordings before and during motor disturbances in sz mutant hamsters showed no abnormalities. The severity of the dystonic syndrome in hamsters is age dependent with a peak at about 30–40 days of age. A score system for grading type and severity of dystonic attack was developed for use in drug activity studies. The severity of the attack was reduced or attacks were completely prevented by diazepam (1–2.5 mg/kg i.p.) and valproic acid (100–400 mg/kg i.p.) in a dose‐dependent fashion. The latency to dystonic movements was significantly increased by diazepam but markedly reduced by subconvulsive doses of pentylenetetrazol (40 mg/kg s.c.). Diazepam antagonized the latency‐reducing action of pentylenetetrazol in the hamsters. The pathophysiology and pharmacological sensitivity of the dystonic attacks in these animals remain to be further clarified, but the data indicate that the sz mutant hamsters might represent an interesting genetic model for paroxysmal dystonia. In view of these data, we propose that the hamster mutation should be re‐named dystonic and that the new gene symbol should be designated dtsz.
Adductor laryngeal dystonia (spastic dysphonia): Treatment with local injections of botulinum toxin (Botox)
Authors: Brin Mitchell F. , Blitzer Andrew , Fahn Stanley , Lovelace Robert E. , Gould Wilbur
Published: January 2005

Adductor spastic dysphonia (SD) is a laryngeal dystonia characterized by a choked, constrained voice pattern with breaks in vocal flow. Treatment with a variety of therapies including speech and pharmacotherapy have minimal benefit; only one‐third of patients undergoing recurrent laryngeal nerve section have benefitted at 3 years. We have used local injections of botulinum toxin (Botox) bilaterally into vocalis muscles in 42 patients with SD. Injections were through a teflon‐coated hollow electromyography (EMG) recording needle. Unilateral small doses (2.53.75 U) were of no clinical benefit. Bilateral small doses resulted in sustained improvement lasting 84.4 ± 9.3 days. The degree of improvement was 61.1 ± 4.6%. Common side‐effects included a brief period of breathy hypophonia (8.5 ± 2.5 days) and a mild sensation of choking/aspiration of fluids (1.7 ± 0.6 days); there were no serious adverse effect. Vocal cord paralysis was not necessary for benefit. Follow‐up vocalis muscle EMGs revealed denervation. All patients responded to retreatment (longest follow‐up 3.5 years). Patients with prior recurrent laryngeal nerve surgery and residual uncomplicated dysphonia had similar results. Our results indicate that local injection of low‐dose Botox is the treatment of choice for SD.
Comparison of Sinemet CR4 and standard Sinemet: Double blind and long‐term open trial in parkinsonian patients with fluctuations
Authors: Jankovic Joseph , Schwartz Kenneth , Linden Chris Vander
Published: January 2005

“Wearing‐off” effect, the most common form of levodopa‐induced fluctuations, seems to be related to the short plasma half‐life of the drug. More sustained plasma levodopa levels may be achieved with a new controlledrelease formulation of carbidopa/levodopa, Sinemet CR4. We studied 20 patients, 12 men and 8 women, with Parkinson's disease complicated by “wearing‐off” phenomenon. Mean age was 61.1 ± 8.1 years, duration of symptoms 8.3 ± 2.4 years, and the Hoehn‐Yahr stage 3.0 ± 0.9. In a 12‐week double‐blind study, the average number of tablets administered per day decreased from 5.7 ± 1.2 to 3.8 ± 0.7 when Sinemet CR4 (50/200) was substituted for the standard Sinemet (25/100) (p < 0.001). However, this was at the expense of reducing the “on” time (without dyskinesia) from 9.3 ± 4.6 to 7.5 ± 4.3 (p < 0.05), although the total “on” time did not significantly change. In a long‐term follow‐up of 18 patients, the “on” time with dyskinesia and morning dystonia significantly increased (p < 0.05). There was no significant change in the total daily dosage of levodopa, but the daily number of doses and tablets significantly decreased (p < 0.001). Despite increased dyskinesia, most patients preferred taking fewer tablets and have elected to continue taking Sinemet CR4 instead of standard Sinemet. Sinemet CR4 seems to offer a new and effective strategy for the management of levodopa‐related fluctuations.
Life‐threatening cranial dystonia following trihexyphenidyl withdrawal
Authors: Giménez‐Roldán S. , Mateo D. , Martíin M.
Published: January 2005

A 64‐year‐old woman with blepharospasm, sustained clenching of the jaw, antecollis, and a strained, high‐pitched phonation continued chronic trihexyphenidyl therapy despite the lack of any obvious benefit. Abrupt, accidental withdrawal of trihexyphenidyl triggered severe exacerbation of the cranial dystonia associated with inspiratory stridor and acute respiratory difficulties, prompting emergency admission. On indirect laryngoscopy, hyperadduction of the vocal folds was not the cause of the upper airway obstruction. A more likely cause of the inspiratory obstruction appeared to be forward bending of the neck combined with mouth‐clenching spasms. Reinstitution of intravenous anticholinergic medication provided relatively prompt relief. We caution against abrupt interruption of anticholinergics in patients with severe segmental cranial dystonia, even in those cases in which no benefit is apparent to observers.
Diaphragmatic flutter, the moving umbilicus syndrome, and “belly dancer's” dyskinesia
Authors: Iliceto G. , Thompson P. D. , Day B. L. , Rothwell J. C. , Lees A. J. , Marsden C. D.
Published: January 2005

Five patients presenting with focal abnormal involuntary movements of the abdominal wall are described. One was shown to have diaphragmatic flutter, which may represent a variant of the palatal myoclonus syndrome. The other four had writhing movements and contractions of the abdominal wall at frequencies of approximately 30 per minute. In two of the latter cases, these abdominal movements were profoundly influenced by respiratory manoeuvres. They were quite unlike the movements of spinal myoclonus or axial torsion dystonia. None of the patients were taking drugs that might have provoked their abnormal movements, or had any other evidence of neurological deficit. No cause was established in any of the cases.
Parkinsonism in alcohol withdrawal: A follow‐up study
Authors: Shandling M. , Carlen P. L. , Lang A. E.
Published: January 2005

Transient parkinsonism associated with alcohol intake and withdrawal has previously been described. We followed‐up three patients with acute alcohol withdrawal‐induced parkinsonism 9–11 years after their initial presentation. None showed any evidence of parkinsonism at follow‐up. This suggests that withdrawal‐induced parkinsonism is caused by a completely reversible abnormality in nigrostriatal dopamine transmission, which is unaccompanied by underlying nigral degeneration, as we had previously hypothesized.
Diurnal variability in cranial dystonia
Authors: Montagna Pasquale , Procaccianti Gaetano , Lugaresi Alessandra , Zucconi Marco , Lugaresi Elio
Published: January 2005

Eleven patients with cranial dystonia were investigated for diurnal variations in disability by means of video recordings. Disability increased significantly from morning to evening. The increase was not related to changes in vigilance levels assessed by dynamic electroencephalogram. Cranial movement disorders display diurnal fluctuations that are probably related to endogenous circadian rhythms.