bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cells from normal and myasthenic individuals recognize the human acetylcholine receptor: Heterogeneity of antigenic sites on the α‐subunit
Authors: Melms A. , Malcherek G. , Gern U. , Wiethölter H. , Müller C. A. , Schoepfer R. , Lindstrom J. 
Published: January 2005

AbstractThe α‐subunit of the nicotinic acetylcholine receptor is the major target of the autoimmune response in myasthenia gravis. We investigated the proligerative response of T cells from patients with myasthenia gravis and healthy volunteers to recombinant polypeptides of the human acetylcholine receptor including the full‐length α‐subunit (α1–437). T cells from 20 (71%) of 28 patients and 7 (37%) of 19 healthy volunteers responded in primary cultures. Subsequently, specific T‐cell lines were established: CD4+, CD8−, UCHL1+, and major histocompatibility complex (MHC) class II–restricted. Using a set of fragments of the α‐subunit, major antigenic sites could be localized on the extracellular, N‐terminal part of the molecule as well as close to the C‐terminus. The T‐cell response was heterogeneous, both among different individuals and among T‐cell lines from a single donor. These T cells did not cross‐react with Torpedo acetylcholine receptor, which was previously used as a substitute for human muscle acetylcholine receptor, suggesting that the T cells had a bias for unique human sequences. A single antigenic fragment could be presented in the context of different MHC class II molecules, and different fragrnents could be presented in the context of the same MHC molecule. This supports earlier observations of considerable heterogeneity in dealing with acetylcholine receptor as an autoantigen on the level of both T cells and antigen‐presenting cells. The data also demonstrate that acetylcholine receptor–specific T cells are present in the normal immune repertoire, and emphasize the role of immune regulation for maintaining a state of tolerance.
Human immunodeficiency virus infection in microglia: Correlation between cells infected in the brain and cells cultured from infectious brain tissue
Authors: Brinkmann R. , Schwinn A. , Narayan O. , Zink C. , Kreth H. W. , Roggendorf W. , Dörries R. , Schwender S. , Imrich H. , ter Meulen V. 
Published: January 2005

AbstractIn acquired immunodeficiency syndrome, the lesions of the central nervous system in association with the human immunodeficiency virus are thought to be related to an infection of microglia, although no studies are available in which cultured and physiological characteristics of microglia cells infected in vivo have been examined. In this report, we used brain tissue from a child dying of human immunodeficiency virus infection and show that microglia cells were the main cell population being infected. Moreover, isolated macrophage‐like cells from fresh brain material revealed a close resemblance to peripheral blood macrophages in their content of surface and intracellular antigens. No virus particles or viral antigens were produced by these cells during the first week of cultivation. Productive infection was readily apparent, however, by day 30. This finding illustrates the slow nature of the virus life cycle in these cells and the minimal cytopathology that accompanied the infection.
Bilateral striopallidodentate calcinosis: Cerebrospinal fluid, imaging, and cerebrospinal fluid, imaging, and electrophysiological studies
Authors: Manyam Bala V. , Bhatt Mohit H. , Moore William D. , Devleschoward Allen B. , Anderson Darrel R. , Calne Donald B. 
Published: January 2005

AbstractWe report the genetic, clinical, electrophysiological, and imaging studies in a family with bilateral striopallidodentate calcinosis (Fahr's disease). The intracerebral calcium deposits occurred before onset of the symptoms in the third decade of life. Progressive neurological deterioration occurred in the fifth decade of life in the proband. Cerebrospinal fluid homocarnosine, a central nervous system–specific peptide, was increased twofold in patients with autosomal dominant bilateral striopallidodentate calcinosis; in sporadic cases, there was no detectable homocarnosine and a decreased level of histidine. With advancing age, the amount of calcification increase, but it has not been determined if a critical amount must be reached before symptoms occur. Computerized tomography is superior to magnetic resonance imaging for radiological diagnosis. Despite diffuse striatal calcification, striatal 6‐[18F]fluoro‐L‐dopa uptake did not reveal any difference between patients and control subjects, from which we infer persisting integrity of the nigrostriatal dopaminergic pathway.
Idiopathic recurring stupor: A case with possible involvement of the gamma–aminobutyric acid (GABA)ergic system
Authors: Tinuper P. , Montagna P. , Cortelli P. , Avoni P. , Lugaresi A. , Schoch P. , Bonetti E. P. , Gallassi R. , Sforza E. , Lugaresi E. 
Published: January 2005

AbstractA patient had recurrent spontaneous episodes of stupor or coma in the absence of toxic, metabolic, or structural brain damage. Ictal electroencephalography showed fast 14 Hz background activity; sleep studies excluded narcolepsy. Flumazenil (Anexate), a benzodiazepine antagonist, promptly resolved the episodes and normalized the electroencephalogram. Radioreceptor binding studies showed the presence of a ligand to the central benzodiazepine receptor in plasma and cerebrospinal fluid during the episodes, suggesting a gamma‐aminobutyric acid (GABA)ergic system involvement in the origin of the attacks.
Detection of coronavirus RNA and antigen in multiple sclerosis brain
Authors: Murray Ronald S. , Brown Bonnie , Brain David , Cabirac Gary F. 
Published: January 2005

AbstractEpidemiological studies of patients with multiple sclerosis (MS) and animal model data support the hypothesis that viruses initiate the immunopathogenic events leading to demyelination in MS. There have been no reports, however, of consistent detection of viruses in MS central nervous system tissue. We probed MS and control brain with cDNA probes specific for human, murine, porcine, and bovine coronaviruses. We report the in situ hybridization detection of coronavirus RNA in 12 of 22 MS brain samples using cloned coronavirus cDNA probes. In addition, tissue was screened for coronavirus antigen by immunohistochemical methods; antigen was detected in two patients with rapidly progressive MS. Significant amounts of coronavirus antigen and RNA were observed in active demyelinating plaques from these two patients. These findings show that coronaviruses can infect the human central nervous system and raise the possibility that these viruses may contribute to the pathogenesis of MS in some patients.
Differences in sensitivity to hyperglycemic hypoxia of isolated rat sensory and motor nerve fibers
Authors: Schneider U. , Jund R. , Nees S. , Grafe P. 
Published: January 2005

AbstractWe explore whether the prevalence of sensory deficits in diabetic neuropathy can be explained by diffuse endoneurial hypoxia. Isolated ventral and dorsal rat spinal roots incubated in 2.5 or 25 mM extracellular glucose were transiently exposed to hypoxia (30 min) in a solution of low buffering power. Compound nerve action potentials and extracellular direct current potentials were continuously recorded before, during, and after hypoxia. In both ventral and dorsal roots incubated in 2.5 mM glucose, sensitivity to hypoxia and posthypoxic recovery were similar. In contrast, hypoxia in 25 mM glucose preferentially induced electrophysiological damage in dorsal roots as indicated by a lack of posthypoxic recovery. This observation was not made in the presence of 25 mM bicarbonate, which suggests involvement of nerve acidosis. In conclusion, the different sensitivity of sensory and motor fibers to hyperglycemic hypoxia supports the hypothesis that hypoxia has an important role in the pathogenesis of diabetic neuropathy.
Quantitative magnetic resonance imaging in temporal lobe epilepsy: Relationship to neuropathology and neuropsychological function
Authors: Lencz Todd , McCarthy Gregory , Bronen Richard A. , Scott Tammy M. , Inserni Jaime A. , Sass Kimberlee J. , Novelly Robert A. , Kim Jung H. , Spencer Dennis D. 
Published: January 2005

AbstractMagnetic resonance images (MRIs) were obtained from 25 patients with medically refractory epilepsy of temporal lobe origin (12 on the left, 13 on the right) and 14 right‐handed control subjects. The hippocampi and temporal lobes were traced by computer on successive coronal images and the resulting measurements of area were summed for each region. The left and right hippocampi were symmetrical in the control subjects; however, for patients the hippocampus was smaller on the side of the seizure focus. Moreover, the left‐right hippocampal ratio significantly differentiated the control subjects from each patient group. The left temporal lobe was significantly smaller than the right in control subjects. The epileptics' temporal lobes were smaller on the side of the seizure focus, compared to the temporal lobes in the control subjects. MRI hippocampal measurements were compared to hippocampal neuronal densities obtained postoperatively. Significant correlations were obtained between the ration (side ipsilateral to focus/side contralateral to focus) of MRI hippocampal measurements and neuronal densities in all hippocampal subfields except CA2. Prior to surgery, patients were administered the Wechsler Memory Scale and the verbal Selective Reminding Test. Significant correlations existed between MRI measurements of the left hippocampus and the Wechsler logical memory percent retention scores and between the left temporal lobe measurements and the verbal Selective Reminding Test scores for patients with seizure foci in the left temporal lobe.
Neurological complications following liver transplantation
Authors: Stein Daniel P. , Lederman Richard J. , Vogt David P. , Carey William D. , Broughan Thomas 
Published: January 2005

AbstractNeurological complications occurred in 4 (19%) of 21 consecutive patients (Group II) undergoing orthotopic liver transplantation, compared with a 47% (9/19) incidence in our initial series (Group I). In Group II, the neurological problems included new recurrent headaches and delayed intracerebral hemorrhage (1 patient), partial third nerve palsy and brachial plexopathy (1 patient), and ataxic dysarthria with encephalopathy (2 patients). Seizures, noted in 8 of 9 neurologically affected Group I patients, were not encountered in Group II. Of the 4 patients in the entire series with the cerebrocerbellar syndrome, 2 had partial recovery after stopping treatment with cyclosporine, 1 stabilized when cyclosporine was discontinued but later worsened when rechallenged, and 1 had full recovery but died following a second transplantation. Brain magnetic resonance images appeared normal in 3 of the 4 patients. Complications affecting vision included cortical blindness in 2 patients and occipital lobe hemorrhage in 1. All completely recovered. Survival was comparable for patients with and those without neurological complications (69% and 63%, respectively). Immediate withdrawal of cyclosporine at the onset of a change in mental status or dysarthria and improvement in intra‐and postoperative management may have contributed to the decreased incidence of neurological complications.
Functional neuroimaging strategy in temporal lobe epilepsy: A comparative study of 18FDG‐PET and 99mTc‐HMPAO–SPECT
Authors: Ryvlin Philippe , Philippon Bernard , Cinotti Luc , Froment Jean C. , Le Bars Didier , Mauguière François 
Published: January 2005

AbstractWe performed 99mTc‐hexamethylpropyleneamineoxime–single‐photon emission computed tomography (SPECT) and 18F‐fluorodeoxyglucose‐positron emission tomography (PET) in 20 epileptic patients with well‐lateralized temporal electroencephalographic focus, normal computed tomographic scan, and brain magnetic resonance imaging (MRI) either normal (n = 10) or showing nonspecific changes in the epileptogenic temporal lobe (n = 10). In patients with a normal MRI, PET exhibited focal hypometabolism in 80%, whereas SPECT showed corresponding hypoperfusion in only 20%. In patients with an abnormal MRI, PET and SPECT yielded 100% and 90% sensitivity, respectively. The metabolic and regional cerbral blood flow disturbances were topographically concordant with electroencephalographic and MRI findings in all these patients. Only patients with a large and pronounced hypometabolism on PET images exhibited hypoperfusion on SPECT. Spatial resolution appeared to be the critical factor responsible for the higher sensitivity of PET. However, this superiority of PET did not prove clinically useful in patients whose SPECT was abnormal, particularly when brain MRI showed nonspecific changes in the epileptogenic temporal lobe.
The twentieth century
Authors: Asbury Arthur K. , Aring Charles D. 
Published: January 2005

AbstractNeurology in the twentieth century has undergone extraordinary change, particularly in the past 40 years. We trace the major trends, including the growth of the field, the technological advances, the revolution in neuroscience, the emergence of neurology as a free‐standing specialty, the rise of child neurology, and the development of neurological subspecialization. Subsequent articles in this series will expand on these subjects.
A novel point mutation in the mitochondrial tRNALeu(UUR) gene in a family with mitochondrial myopathy
Authors: Goto Yu‐ichi , Tojo Megumu , Tohyama Jun , Horai Satoshi , Nonaka Ikuya 
Published: January 2005

AbstractA T‐to‐C transition mutation at nucleotide position 3,250 in the mitochondrial tRNALeu(UUR) gene was present in a family with mitochondrial myopathy. Two of three muscle biopsies examined had complex I (NADH‐ubiquinone oxidoreductase) deficiency. Heteroplasmy of wild and mutant mitochondrial DNA was detected by Nae I digestion of the polymerase chain reaction products with a modified primer. This was found in blood or muscle samples or both from all seven members examined. Similar to the 3,243 mutation in most patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes), the new mutation site was located in the dihydrouridine loop and embedded in the binding region of mitochondrial transcription termination factor. Elucidation of the effects of this mutation may help clarify the role of mitochondrial tRNAs and transcription termination.
Quantitation of T‐cell receptor Vβ chain expression on lymphocytes from blood, brain, and spinal fluid in patients with multiple sclerosis and other neurological diseases
Authors: Birnbaum Gary , Van Ness Brian 
Published: January 2005

AbstractMultiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system in which large numbers of T cells enter the brain and cerebrospinal fluid (CSF). To determine whether these cells represent restricted populations, we studied expression of T‐cell receptor Vβ chains on paired samples from the central nervous system and blood of patients with MS or other neurological diseases (OND) using a quantitative polymerase chain reaction. The distribution of Vβ chain expression in blood was skewed, with a significant preponderance of message from Vβ genes 1 through 8 (p = 0.0001). Such skewing was not present in samples from the CSF and brain. Patterns of Vβ gene expression were different among paired samples from spinal fluid and blood and were relatively heterogeneous. Blood and CSF samples from a patient with acute meningitis were studied on two separate occasions. The patterns of Vβ expression changed over 72 hours in both the blood and the CSF. With one exception, no oligoclonal populations of T cells were observed nor were there disease‐specific patterns of Vβ gene expression in the blood or CSF. Samples from 2 MS brains and 1 OND brain expressed patterns of Vβ genes that were different and less heterogeneous than those in paired blood. In addition, expression of Vβ 12 was remarkably increased in the 2 MS brains, suggesting a selective recruitment or expansion of T cells expressing this gene. These data demonstrate that populations of T cells from blood, spinal fluid, and brain differ from one another and can fluctuate during periods of acute inflammation. In addition, studies of brain T cells may be more informative in terms of defining oligoclonal populations of potentially pathogenic T cells than will studies of nonselected CSF T cells.
Lack of major olfactory dysfunction in MPTP‐induced parkinsonism
Authors: Doty Richard L. , Singh Anu , Tetrud James , Langston J. William 
Published: January 2005

AbstractThe olfactory function of 6 patients whose parkinsonism was the result of intravenous administration of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) was compared to that of 12 age‐matched patients with idiopathic Parkinson's disease (PD) and 10 age‐matched normal control subjects. Unlike their PD counterparts, the olfactory test scores of patients with MPTP‐induced parkinsonism, did not differ significantly from those of control subjects. These findings suggest that MPTP induced parkinsonism, unlike idiopathic PD, is unaccompanied, on average, by major alterations in the ability to smell.
Angiotensin II receptor binding associated with nigrostriatal dopaminergic neurons in human basal ganglia
Authors: Allen Andrew M. , MacGregor Duncan P. , Chai Siew Y. , Donnan Geoffrey A. , Kaczmarczyk Stanislav , Richardson Karen , Kalnins Renata , Ireton John , Mendelsohn Frederick A. O. 
Published: January 2005

AbstractIn the human brain, receptor binding sites for angiotensin are found in the striatum and in the substantia nigra pars compacta overlying dopamine‐containing cell bodies. In contrast, angiotensin‐converting enzyme occurs in the substantia nigra pars reticulata and is enriched in the striosomes of the striatum. In this study, using quantitative in vitro autoradiography, we demonstrate decreased angiotensin receptor binding in the substantia nigra and striatum of postmortem brains from patients with Parkinson's disease. In the same brains the density of binding to angiotensin‐converting enzyme shows no consistent change. We propose, from these results, that angiotensin receptors in the striatum are located presynaptically on dopaminergic terminals projecting from the substantia nigra. In contrast, the results support previous studies in rats demonstrating that angiotensin‐converting enzyme is associated with striatal neurons projecting to the substantia nigra pars reticulata. These findings raise the possibility that newly emerging drugs that interact with the angiotensin system, particularly converting enzyme inhibitors and new nonpeptide angiotensin receptor blockers, may modulate the brain dopamine system.
Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease
Authors: Stern Yaakov , Alexander Gene E. , Prohovnik Isak , Mayeux Richard 
Published: January 2005

AbstractA higher prevalence of dementia in individuals with fewer years of education has suggested that education may protect against Alzheimer's disease (AD). We tested whether individuals with more years of education have a more advanced AD before it is clinically evident. As a measure of pathophysiological severity, we quantified regional cerebral blood flow (rCBF), by the 133Xenon inhalation technique; a specific pattern of flow reduction in the parietotemporal cortex corresponds to AD pathology. In 3 groups of patients with probable AD, matched for clinical measures of dementia severity but with varying levels of education, whole‐cortex mean flows were comparable. However, the parietotemporal perfusion deficit was significantly greater in the group with the highest level of education, indicating that AD was more advanced in this group. We conclude that education or its covariates or both may provide a reserve that compensates for the neuropathological changes of AD and delays the onset of its clinical manifestations.
Amygdala cell loss and atrophy in Alzheimer's disease
Authors: Scott Samuel A. , Sparks D. Larry , Scheff Stephen W. , Dekosky Steven T. , Knox Craig A. 
Published: January 2005

AbstractThe amygdala and its subnuclei undergo severe volumetric atrophy in Alzheimer's disease (AD). To determine whether this atrophy is due to loss of neuropil, specific neuronal populations, or both, we evaluated the number, size, and packing density of neurons and glia in the cortical and magnocellular basal amygdaloid subregions. The neuropil fraction did not change with AD in either region. Despite a mean 35% increase in cell packing density in the AD amygdala, total numbers of neurons and glia within tissue sections were reduced significantly; medium and large neurons were preferentially affected. The total number of small neurons was stable in the AD sample despite sharp reductions in nuclear size, suggesting that AD also results in pronounced amygdaloid neuronal shrinkage. Differences in the degree of cell loss between the two nuclei as well as changes in glial cell numbers are discussed in relation to characteristic AD neuropathology and relevant anatomical connectivity.
Severity of X‐linked recessive bulbospinal neuronopathy correlates with size of the tandem cag repeat in androgen receptor gene
Authors: Doyu Manabu , Sobue Gen , Mukai Eiichiro , Kachi Teruhiko , Yasuda Takeshi , Mitsuma Terunori , Takahashi Akira 
Published: January 2005

AbstractThe genetic mutation of X‐linked recessive bulbospinal neuronopathy is amplification of a polymorphic tandem CAG repeat in the androgen receptor gene. We studied this CAG repeat in 26 Japanese patients from 21 families with X‐linked recessive bulbospinal neuronopathy. The number of CAG repeats was significantly correlated with the age at onset of limb muscular weakness (r = −0.596, p < 0.001) and age‐adjusted scored disability (r = 0.446, p < 0.03). The length of the CAG repeat therefore seems to be a determinant factor of clinical severity.
The trigeminovascular system and migraine: Studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats
Authors: Goadsby Peter J. , Edvinsson Lars 
Published: January 2005

AbstractBoth clinical and physiological consideration of migraine suggests that the pathophysiology of the syndrome is intimately linked to the trigeminal innervation of the cranial vessels, the trigeminovascular system. Studies were conducted on cats and humans to examine the interaction of these systems with the effective acute antimigraine drugs dihydroergotamine and sumatriptan. In the animal studies cats were anesthetized and prepared for routine physiological monitoring as well as for blood sampling from the external jugular veins. Cerebral blood flow was monitored continuously using laser Doppler flowmetry and the effect of trigeminal ganglion stimulation on both cerebral blood flow and jugular vein peptide levels determined prior to and after administration of either sumatriptan or dihydroergotamine. Stimulation of the trigeminal ganglion led to a frequency‐dependent increase in cerebral blood flow, with a mean maximum of 43 ± 9% at a stimulus frequency of 20 per second. There was a marked reduction in these responses by some 50% after administration of either sumatriptan or dihydroergotamine. Trigeminal ganglion stimulation at a frequency of 5 per second also led to a release into the cranial circulation of calcitonin gene–related peptide (CGRP), with the level rising from 67 ± 3 to 82 ± 5 pmol/liter on the side of stimulation. These increases were also markedly antagonized by both sumatriptan and dihydroergotamine. Human studies were conducted as part of the overall evaluation of sumatriptan for the treatment of acute migraine. In 7 of 8 patients responding to subcutaneous sumatriptan administration, elevated CGRP levels (60 ± 8 pmol/liter) were normalized, with the headache being relieved (40 ± 8 pmol/liter). These data characterize some aspects of the cerebrovascular physiology of the trigeminovascular system and demonstrate important interactions between this system and the effective antimigraine agents sumatriptan and dihydroergotamine and that such interactions can be represented in animal models.