bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acetylcholine release in myasthenia gravis: Regulation at single end‐plate level
Authors: Plomp Jaap J. , van Kempen Gertrudis TH. H. , de Baets Marc BscH. , Graus Yvo M. F. , Kuks Jan B. M. , Molenaar Peter C. 
Published: January 2005

AbstractIn myasthenia gravis, loss of acetylcholine receptors at motor end‐plates is induced by antireceptor autoantibodies. At end‐plates in rats in which myasthenia gravis–like symptoms are induced by chronic treatment with α‐bungarotoxin, acetylcholine release is increased. Within muscles from such rats there is a strong correlation between the increase of acetylcholine release at an end‐plate and the loss of postsynaptic acetylcholine receptors, caused by the toxin. The question is whether upregulation of acetylcholine release is a clinically relevant compensatory mechanism in myasthenia gravis or only a feature of the animal model using α‐bungarotoxin. We investigated electrophysiologically the in vitro acetylcholine release at end‐plates of muscles from patients with myasthenia gravis and rats with experimental autoimmune myasthenia gravis where acetylcholine receptor reduction is caused by autoantibody attack. In both human and rat autoimmune myasthenic muscle, the mean quantal content was considerably increased compared with control levels. At each individual myasthenic end‐plate, the increase in quantal content appeared to be correlated with the reduction of the amplitude of the miniature end‐plate potential. This finding suggests the existence of an important compensatory mechanism in myasthenia gravis, in which retrograde acting factors (i.e., from muscle fiber to nerve terminal) upregulate acetylcholine release.
The vasculopathy of varicella‐zoster virus encephalitis
Authors: Amlie‐Lefond Catherine , Kleinschmidt‐Demasters Bette K. , Mahalingam Ravi , Davis Larry E. , Gilden Donald H. 
Published: January 2005

AbstractVaricella‐zoster virus (VZV) encephalitis has become more prevalent in the era of acquired immunodeficiency syndrome and other immunosuppressive diseases and poses diagnostic and therapeutic challenges for clinicians, radiologists, and pathologists. Six cases studied at our institutions shed light on the patterns and pathogenesis of the disease. VZV encephalitis is predominantly a vasculopathy, involving small and large vessels, that generates seizures, mental changes, and focal deficits. Brain imaging reveals large and small ischemic or hemorrhagic infarcts, often both, of cortex and subcortical gray and white matter. Deep‐seated white matter lesions often predominate and are ischemic and/or demyelinative, depending on the size of blood vessels involved and the amount of additional demyelination caused by infection of oligodendrocytes. The demyelinative lesions are smaller and less coalescent than those seen in progressive multifocal leukoencephalopathy.
Interleukin‐6 and interleukin‐1 receptor antagonist in acute stroke
Authors: Beamer Nancy B. , Coull Bruce M. , Clark Wayne M. , Hazel J. Samantha , Silberger Jenny R. 
Published: January 2005

AbstractElevated plasma levels of interleukin‐6 (IL‐6), a key regulator of the acute phase response that includes increased fibrinogen synthesis, have recently been detected in patients with acute stroke. Nevertheless, the role of the acute phase response in stroke has been controversial, with some studies suggesting that preexisting infection accounts for most of the acute phase response. Increased IL‐6 could signal the involvement of antiinflammatory activity, since IL‐6 stimulates the production of endogenous antiinflammatory mediators such as interleukin‐1 receptor antagonist (IL‐1RA). To better understand the interaction of pro‐ and antiinflammatory acute phase processes in brain infarction, plasma levels of IL‐1RA, IL‐6, and acute phase proteins including fibrinogen and c‐reactive protein (CRP) were measured within 4 ± 2 days of onset in 50 patients with acute ischemic stroke and in 20 age‐matched healthy controls. After excluding patients with evidence of infection, both IL‐1RA and IL‐6 were significantly elevated in stoke patients compared with controls (p<0.0001). IL‐1RA and IL‐6 were both significantly correlated with levels of CRP, p<0.05 and p<0.001, respectively, but not with each other. Levels of IL‐6 and IL‐1RA, together with fibrinogen and CRP were higher in patients with infarcts of greater than 3 cm and lowest in patients with lacunar syndromes. Detection of increased peripheral levels of IL‐1RA, IL‐6, and additional acute phase reactants, including CRP, in acute stroke uncomplicated by infection suggests that an acute phase response to brain infarction occurs and that the magnitude of this response may be related to the volume of infarcted brain.
Regional distribution of protease‐resistant prion protein in fatal familial insomnia
Authors: Parchi Piero , Castellani Rudy , Cortelli Pietro , Montagna Pasquale , Chen Shu G. , Petersen Robert B. , Manetto Valeria , Vnencak‐Jones Cindy L. , McLean Michael J. , Sheller James R. , Lugaresi Elio , Autilio‐Gambetti Lucila , Gambetti Pierluigi 
Published: January 2005

AbstractProtease‐resistant prion protein, total prion protein, and glial fibrillary acidic protein were measured in various brain regions from 9 subjects with fatal familial insomnia. Six were homozygotes methionine/methionine at codon 129 (mean duration, 10.7 ± 4 months) and 3 were heterozygotes methionine/valine (mean duration, 23 ± 11 months). In all subjects, protease‐resistant prion protein was detected in gray matter but not in white matter and peripheral organs. Its distribution was more widespread than that of the histopathological lesions, which were observed only in the presence of a critical amount of the abnormal protein. In the mediodorsal thalamic nucleus, however, a severe neuronal loss and astrogliosis were associated with relatively moderate amounts of protease‐resistant prion protein, suggesting a higher vulnerability. There was no overall correlation between amount of protease‐resistant prion protein and either glial fibrillary acidic protein or total prion protein. While protease‐resistant prion protein was virtually limited to subcortical areas and showed a selective pattern of distribution in the subjects with disease of the shortest duration, it was more widespread in the subjects with a longer clinical course, indicating that with time the disease process spreads within the brain. The kinetics of the accumulation of protease‐resistant prion protein varied among different brain regions: While in the neocortex and to a lesser extent in the limbic lobe and in the caudate nucleus, the amount increased with disease duration, in the mediodorsal thalamic nucleus and in the brainstem it was present in comparable amounts in all subjects regardless of the disease duration. These findings indicate that in fatal familial insomnia, the pathological phenotype is the result of the variability, in different brain regions, of the (1) timing and rate of accumulation of protease‐resistant prion protein, and (2) vulnerability to the presence of protease‐resistant prion protein.
Mutational analysis of familial and sporadic hyperekplexia
Authors: Shiang Rita , Ryan Stephen G. , Zhu Ya‐Zhen , Fielder Thomas J. , Allen Richard J. , Fryer Alan , Yamashita Sumimasa , O'Connell Peter , Wasmuth John J. 
Published: January 2005

AbstractHyperekplexia is a rare, autosomal dominant neurological disorder characterized by hypertonia, especially in infancy, and by an exaggerated startle response. This disorder is caused by mutations in the ϵ1 subunit of the inhibitory glycine receptor (GLRA1). We previously reported two GLRA1 point mutations detected in 4 unrelated hyperekplexia families; both mutations were at nucleotide 1192 and resulted in the replacement of Arg271 by a glutamine (R271Q) in one case and a leucine (R271L) in the other. Here, 5 additional hyperekplexia families are shown to have the most common G‐to‐A transition mutation at nucleotide 1192. Haplotype analysis using polymorphisms within and close to the GLRA1 locus suggests that this mutation has arisen at least twice (and possibly four times). In 2 additional families, a third mutation is also presented that changes a tyrosine at amino acid 279 to a cysteine (Y279C). Five patients with atypical clinical features and equivocal or absent family history of hyperekplexia and 1 patient with a classical presentation but no family history are presented in whom a mutation in the GLRA1 gene was not detected. Thus, only clinically typical hyperekplexia appears to be consistently associated with GLRA1 mutations, and these affect a specific extracellular domain of the protein.
Epistatic effect of APP717 mutation and apolipoprotein E genotype in familial Alzheimer's disease
Authors: Sorbi Sandro , Nacmias Benedetta , Forleo Paolo , Piacentini Silvia , Latorraca Stefania , Amaducci Luigi 
Published: January 2005

AbstractWe found a new familial Alzheimer's disease kindred in which the disease cosegregates with the APP717Val‐→Ile mutation and in which all of the three most common apolipoprotein E (ApoE) alleles are represented. We studied the relationship between ApoE genotype and the clinical expression of the disease and found that in this amyloid precursor protein‐mutated family, ApoE genotype influences the age at onset of the disease. Three mutated subjects heterozygous for the ϵ4 allele had the earliest age at onset in this family, subjects heterozygous for the ϵ2 allele had the latest age at onset, and subjects homozygous for the ϵ3 allele had an intermediate age at onset. In this large kindred we also found an amyloid precursor protein‐mutated subject 2.4 standard deviations older than the mean age at onset without clinical signs and symptoms of the disease and carrying the ϵ2/ϵ3 genotype.
Multifocal enhancing magnetic resonance imaging lesions following cranial irradiation
Authors: Peterson Kendra , Brent Clark H. , Hall Walter A. , Truwit Charles L. 
Published: January 2005

AbstractRadiation necrosis is a delayed complication of cranial irradiation, typically presenting as a single intracerebral mass that is radiographically indistinguishable from recurrent tumor. We describe 6 patients with a distinct radiographic syndrome of multifocal enhancing lesions on magnetic resonance images, and their variable clinical courses: some fluctuating, some spontaneously resolving, and some demonstrating fulminant progression to frank necrosis.
Cellular activity underlying altered brain metabolism during focal epileptic activity
Authors: Bruehl Claus , Witte Otto W. 
Published: January 2005

AbstractDemonstration of focal alterations of brain metabolism with positron emission tomography has become a widely used method for identifying epileptic foci. Here we investigated how neuronal and glial cell activity relates to alterations of brain metabolism. Acutely induced epileptic activity in the motor cortex of rat brain increased metabolism in the focus and homotopic contralateral areas, and decreased metabolism in the ipsilateral somatosensory area. Increases and decreases of deoxyglucose uptake did not directly correlate with excitations and inhibitions; instead, deoxyglucose uptake was related to the overall strength of synaptic activity, and both strong excitations and strong inhibitions increased brain metabolism. Reduction of metabolism below normal values was associated with reduced synaptic activity and with tonic hyperpolarization of the cells. Our results show that in the absence of structural abnormalities, hypometabolism indicates functional disturbances which may be both reversible and remote from the epileptogenic focus.
Influx of nonactivated T lymphocytes into the cerebrospinal fluid during relapse of multiple sclerosis
Authors: Oksaranta Olli , Tarvonen Sinikka , Ilonen Jorma , Poikonen Kari , Reunanen Mauri , Panelius Martin , Salonen Reijo 
Published: January 2005

AbstractT lymphocytes were analyzed in the cerebrospinal fluid of 17 patients with multiple sclerosis during and 2 months after an exacerbation. The percentage of activated (HLA‐DR+) T lymphocytes was decreased in the cerebrospinal fluid during the relapse but returned thereafter to the level comparable to that in patients with noninflammatory neurological diseases, whereas no fluctuation in the total number of these cells was found. This suggests an influx of nonactivated T lymphocytes into the cerebrospinal fluid at the beginning of the relapse.
The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's disease
Authors: Chen Xiaohua , Xia Yu , Alford Michael , DeTeresa Richard , Hansen Lawrence , Klauber Melville R. , Katzman Robert , Thal Leon , Masliah Eliezer , Saitoh Tsunao 
Published: January 2005

AbstractBoth genetic and environmental factors affect the progression of Alzheimer's disease (AD). The presence of cortical Lewy bodies in AD patients is associated with an altered presentation of AD pathology suggestive of an interaction between the pathogenesis of Lewy bodies and AD lesions. Since the CYP2D6B mutant allele is often present in patients with Lewy body diseases (Parkinson's disease and Lewy body variant of AD), we extended these prior observations by studying the neuropathology associated with the presence of the CYP2D6B mutant allele, in a pure AD population without Lewy bodies. AD patients who possessed the CYP2D6B mutant allele, in comparison with those without the CYP2D6B allele, were found to have a smaller decline in two synaptic Marchkers, choline acetyltransferase and synaptophysin, in the frontal cortex relative to normal control values. On the other hand, senile plaques and neurofibrillary tangles were not significantly affected by the presence of the CYP2D6B mutant allele in the frontal cortex of AD patients. Association of the CYP2D6B mutant allele with Lewy body formation in both Parkinson's disease and the Lewy body variant of AD and with the milder synaptic pathology in pure AD without Lewy bodies suggest that depending on the contribution of other genetic and environmental factors, this mutant allele may be involved with different aspects of neurodegeneration.
Aphasia in acute stroke: Incidence, determinants, and recovery
Authors: Pedersen Palle Møller , Stig Jørgensen Henrik , Nakayama Hirofumi , Raaschou Hans Otto , Olsen Tom Skyhøj 
Published: January 2005

AbstractKnowledge of the frequency and remission of aphasia is essential for the rehabilitation of stroke patients and provides insight into the brain organization of language. We studied prospectively and consecutively an unselected and community‐based sample of 881 patients with acute stroke. Assessment of aphasia was done at admission, weekly during the hospital stay, and at a 6‐months follow‐up using the aphasia score of the Scandinavian Stroke Scale. Thirty‐eight percent had aphasia at the time of admission; at discharge 18% had aphasia. Sex was not a determinant of aphasia in stroke, and no sex difference in the anterior‐posterior distribution of lesions was found. The remission curve was steep: Stationary language function in 95% was reached within 2 weeks in those with initial mild aphasia, within 6 weeks in those with moderate, and within 10 weeks in those with severe aphasia. A valid prognosis of aphasia could be made within 1 to 4 weeks after the stroke depending on the initial severity of aphasia. Initial severity of aphasia was the only clinically relevant predictor of aphasia outcome. Sex, handedness, and side of stroke lesion were not independent outcome predictors, and the influence of age was minimal.
Neuroborreliosis in the nonhuman primate: Borrelia burgdorferi persists in the central nervous system
Authors: Pachner Andrew R. , Delaney Elizabeth , O'Neill Tim 
Published: January 2005

AbstractNeurological involvement in Lyme disease is common, and is frequently difficult to diagnose and treat. Little is known about the fate of the causative spirochete Borrelia burgdorferi in the central nervous system (CNS). To determine the frequency of parenchymal infection and to determine localization of the organism, polymerase chain reaction/hybridization assays were performed in a newly described model of Lyme neuroborreliosis in nonhuman primates infected with B. burgdorferi. Polymerase chain reaction/hybridization of CNS tissues from 5 infected nonhuman primates was performed. Substantial amounts of B. burgdorferi DNA were detected in the CNS in all infected animals, with a predilection toward subtentorial structures. These data suggest that Lyme neuroboreliosis represents persistent infection with B. burgdorferi.
Chronic inflammatory demyelinating polyneuropathy complicating liver transplantation
Authors: Taylor Bruce V. , Wijdicks Eelco F. M. , Poterucha John J. , Weisner Russel H. 
Published: January 2005

AbstractWe report on a patient who had chronic inflammatory demyelinating polyradiculoneuropathy following liver transplantation for hepatitis B‐induced fulminate hepatic failure. Possible symptomatic recurrence of hepatitis B in the graft prompted a reduction in the cyclosporine dosage, which may have triggered the immune response leading to demyelination. Initial plasma exchange and then intravenous immune globulin after relapse led to Marchked clinical improvement.
Preferential loss of preproenkephalin versus preprotachykinin neurons from the striatum of Huntington's disease patients
Authors: Richfield Eric K. , Maguire‐Zeiss Kathleen A. , Vonkeman Harald E. , Voorn Pieter 
Published: January 2005

AbstractPreferential loss of basal ganglia neurons and terminals occurs in Huntington's disease (HD). Terminals of preproen‐kephalin medium‐size spiny neurons are more vulnerable than terminals of preprotachykinin neurons, but the peptidergic neurons of origin have not yet been shown to die preferentially. We sought to determine, in the striatum, whether preproenkephalin neurons were lost to a greater extent than preprotachykinin neurons and to determine whether there were decreases in specific messenger RNA (mRNA) levels of preproenkephalin, preprotachykinin, and calbindin D28k. We found a grade‐related decrease in the number of preprotachykinin‐ and calbindin D28k—labeled neurons per measuring field in the caudate nucleus of patients with HD. Three measures of the neuronal level of preprotachykinin mRNA were all significantly reduced (6–65% of control values) in HD caudate nucleus. No decline in calbindin D28k mRNA levels per neuron were found in HD striata compared to control striata. We found a greater loss of preproenkephalin neurons per field than preprotachykinin neurons per field in the caudate nucleus of HD brains compared to control brains. Preprotachykinin neurons are lost in HD in a grade‐related manner and surviving preprotachykinin neurons are impaired in function. However, preproenkephalin neurons are lost to a greater extent than preprotachykinin neurons, which may explain preferential changes found in projection regions of the striatum. Declines in neuropeptide mRNA may be specific in HD, since calbindin D28k mRNA levels were unchanged. Alterations in the levels of expression of preproenkephalin and preprotachykinin mRNA may be direct or indirect effects of the HD mutation.
Cerebellar outflow lesions: A comparison of movement deficits resulting from lesions at the levels of the cerebellum and thalamus
Authors: Bastian A. J. , Thach W. T. 
Published: January 2005

AbstractPrevious work has shown that lesions in the lateral cerebellum involving the dentate nucleus impair both reaching and pinching movements in humans and monkeys. This study addressed the question of whether disruption of the cerebellar‐thalamo‐cortical pathway at the level of the thalamus would produce behavioral deficits similar to those seen after dentate damage. We compared the performance of both reaching and pinching movements in patients with lateral cerebellar lesions and in patients with discrete lesions of the ventrolateral thalamus. The patients with thalamic lesions had minimal or no sensory loss and no corticospinal signs, suggesting that the abnormal movements were due to disruption of the cerebellar projection to the thalamus. We found that lesions of the ventrolateral thalamus resulted in impaired pinching movements, but remarkably normal reaching movements with the exception of a slight tremor. This is in contrast to the profound pinching and reaching impairments of patients with lateral cerebellar lesions involving the dentate nucleus. Implications about the functional organization of cerebellar output are discussed.
Apolipoprotein E ϵ4 in inclusion body myositis
Authors: Garlepp Michael J. , Tabarias Hyacinth , van Bockxmeer Frank M. , Zilko Paul J. , Laing Beverley , Mastaglia Frank L. 
Published: January 2005

AbstractThe genetic predisposition to inclusion body myositis (IBM) is probably multifactorial. The deposition of the β‐amyloid protein is a characteristic histological feature of both IBM and Alzheimer's disease (AD). The ϵ4 allele of apolipoprotein E (APO E) has been strongly associated with familial and late‐onset AD. We therefore compared the APO E allele frequencies in a group of 14 patients with IBM with those in a group of patients with other inflammatory muscle diseases and in the general population. The frequency of the ϵ4 allele in IBM was increased (0.29) compared with that in patients with other inflammatory muscle diseases (0.15) and the general population (0.13) (p < 0.05). These data suggest that APO E genotype may be one of the factors involved in determining the predisposition to the development of IBM.
Pathology of the motor‐sensory axonal Guillain‐Barré syndrome
Authors: Griffin J. W. , Li C. Y. , Ho T. W. , Tian M. , Gao C. Y. , Xue P. , Mishu B. , Cornblath D. R. , Macko C. , McKhann G. M. , Asbury A. K. 
Published: January 2005

AbstractThe concept of a severe motor‐sensory neuropathy of acute onset caused by an immune attack on the axon (“axonal” Guillain‐Barré syndrome) has been advanced primarily based on electrodiagnostic and limited pathological data, but remains controversial. At autopsy some cases demonstrate unusually severe inflammatory demyelinating neuropathy. There are conflicting data about whether antecedent Campylobacter jejuni infection is associated with “axonal” Guillain‐ Barré syndrome. We report 4 individuals from Hebei Province, China, who died 7, 7, 18, and 60 days after onset of a syndrome diagnosed clinically as Guillain‐Barré syndrome. High titers of antibodies recognizing C. jejuni, consistent with recent infection, were found in the 2 patients tested. At autopsy the 3 with early disease had ongoing wallerian‐ like degeneration of fibers in the ventral and dorsal roots and in the peripheral nerves, with only minimal demyelination or lymphocytic infiltration. All 3 had numerous macrophages in the periaxonal space of myelinated internodes, and rare intraaxonal macrophages as well. Examination of the patient having the syndrome for 60 days confirmed the extensive loss of large fibers in the spinal roots and nerves, and the paucity of demyelination and remyelination. These observations confirm predictions that some patients with severe motor‐sensory Guillain‐Barré syndrome, as defined clinically, have predominantly axonal lesions of both motor and sensory fibers, even in the early stages of the disease, and that axonal Guillain‐Barré syndrome can follow C. jejuni infection. The pathology supports the possibility that such cases of motor‐sensory axonal Guillain‐Barré syndrome represent the most severe end of a spectrum of immune attack directed toward epitopes on the axon.