bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐CD11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat
Authors: Chen H. , Chopp M. , Zhang R. L. , Bodzin G. , Chen Q. , Rusche J. R. , Todd R. F. 
Published: January 2005

AbstractWe investigated the effect of an anti‐CD11b monoclonal antibody (1B6c) on ischemic cell damage after transient middle cerebral artery occlusion. We divided animals into three groups: MAb 1 group (n = 5)—rats were subjected to 2 hours of transient occlusion and 1B6c (1 mg/kg) was administered intravenously at 0 and 22 hours of reperfusion; MAb 2 group (n = 5)—same experimental protocol as MAb 1 group, except that the initial dose of 1B6c was increased to 2 mg/kg; and control group (n = 5)—same experimental protocol as MAb 2 group, except that an isotype‐matched control antibody was administered. Animals were weighed and tested for neurological function before and after occlusion of the middle cerebral artery. Forty‐six hours after reperfusion, brain sections were stained with hematoxylin and eosin for histology evaluation. We observed a significant reduction of weight loss and improvement in neurological function after ischemia in the MAb 2 animals compared to MAb 1 and vehicle‐treated animals (p < 0.05). The lesion volume was significantly smaller in the MAb 2 group (19.5 ± 1.9%) compared to MAb1 (29.9 ± 2.6%) and vehicletreated (34.2 ± 5.4%) group (p < 0.01). Tissue polymorphonuclear cell numbers were reduced in both 1B6c‐administered groups. Our data demonstrate that administration of anti‐CD11b antibody results in a dose‐dependent, significant functional improvement and reduction of ischemic cell damage after transient focal cerebral ischemia in the rat.
Elevated serum levels of endothelial leukocyte adhesion molecules in Guillain‐Barré syndrome and chronic inflammatory demyelinating polyneuropathy
Authors: Oka Nobuyuki , Akiguchi Ichiro , Kawasaki Teruaki , Ohnishi Katsunori , Kimura Jun 
Published: January 2005

AbstractWe determined the serum concentrations of the soluble form of endothelial leukocyte adhesion molecule‐1 (sELAM‐1) in 25 patients with Guillain‐Barré syndrome, 14 patients with chronic inflammatory demyelinating polyneuropathy, 15 patients with amyotrophic lateral sclerosis, 15 patients with other polyneuropathies, 10 patients with acute stroke, and 12 healthy control subjects. The patients with Guillain‐Barré syndrome in the acute stage had a higher sELAM‐1 serum level compared with the control subjects (p < 0.001). In 7 of the 9 patients the elevated level returned to normal by 14 days after the onset of neurological symptoms. In addition, a significantly elevated serum level of sELAM‐1 was found in patients with chronic inflammatory demyelinating polyneuropathy (p < 0.01). These findings suggest a role for ELAM‐1 in the inflammatory process of these disorders.
Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson's disease
Authors: Greenamyre J. Timothy , Eller Robert V. , Zhang Zhiming , Ovadia Aliza , Kurlan Roger , Gash Don M. 
Published: January 2005

AbstractLoss of dopaminergic innervation of the striatum results in overactivity of the glutamatergic pathways from the subthalamic nucleus to the internal segment of the globus pallidus and the substantia nigra pars reticulata, the output nuclei of the basal ganglia. Previous work has shown that local blockade of glutamate receptors in the internal segment of the globus pallidus or substantia nigra pars reticulata leads to marked suppression of parkinsonian signs. We have now examined whether systemic administration of a glutamate receptor antagonist has antiparkinsonian effects in rodent and primate models of Parkinson's disease. Remacemide hydrochloride is an anticonvulsant, neuroprotective compound with antagonist activity at the N‐methyl‐D‐aspartate receptor ion channel. In normal rats and monoaminedepleted rats, remacemide hydrochloride did not cause locomotor hyperactivity, unlike MK‐801. When monoaminedepleted rats were treated with a subthreshold dose of levodopa methylester, remacemide hydrochloride (5–40mg/kg, orally) caused a dose‐dependent increase in locomotor activity. Moreover, remacemide hydrochloride (10 mg/kg, orally) potentiated the effects of each suprathreshold dose of levodopa methylester tested (100–200 mg/kg, intraperitoneally). Parkinsonian rhesus monkeys were tested with oral doses of vehicle plus vehicle, vehicle plus levodopa‐carbidopa, and remacemide hydrochloride (5 mg/kg) plus levodopa‐carbidopa. Blinded clinical scoring of videotapes revealed that treatment with remacemide hydrochloride plus levodopa‐carbidopa was substantially better than levodopa‐carbidopa plus vehicle or vehicle plus vehicle. The effects of remacemide hydrochloride lasted at least 5 hours. We conclude that certain N‐methyl‐D‐aspartate receptor antagonists have antiparkinsonian actions and low potential for side effects. Clinical trials of remacemide hydrochloride in patients with Parkinson's disease may be warranted.
Pyruvate dehydrogenase deficiency: Molecular basis for intrafamilial heterogeneity
Authors: Fujii Tatsuya , Van Coster Rudy N. , Old Susan E. , Medori Rosella , Winter Susan , Gubits Ruth M. , Matthews Paul M. , Brown Ruth M. , Brown Garry K. , Dahl Hans‐Henrik M. , De Vivo Darryl C. 
Published: January 2005

AbstractTwo half‐brothers and their mother had symptomatic pyruvate dehydrogenase complex deficiency. The infants had severe congenital lactic acidosis, seizures, and apneic spells and died at the ages of 3 and 4 months. The mother was less symptomatic with mental retardation, truncal ataxia, and dysarthria. The residual pyruvate dehydrogenase activities in cultured skin fibroblasts from the 2 infants and their mother were 7, 15, and 10% of control values. Immunoblot analysis showed negligible amounts of E1α and E1β subunits of the complex. Northern blot analysis for the E1α subunit showed normal results. In the 2 sons, complementary DNA sequence analysis reveled a cytosine to thymine mutation in exon 4, resulting in a change of arginine 127 to tryptophan in the E1α subunit. Restriction enzyme analysis of the polymerase chain reaction product representing exon 4 of the E1α gene revealed that the mother was a heterozygote. Complementary DNA restriction analysis and methylation analysis of the X chromosome DXS255 loci revealed skewed activation of the mutant allele, consistent with the deficient pyruvate dehydrogenase activity in the mother's fibroblasts. The milder maternal phenotype is consistent with variable X‐inactivation patterns in different organs of female heterozygotes.
Subacute sclerosing panencephalitis in an infant: Diagnostic role of viral genome analysis
Authors: Baram Tallie Z. , Gonzalez‐Gomez Ignacio , Xie Zong‐De , Yao Dapeng , Gilles Floyd H. , Nelson Marvin D. , Nguyen Hahn T. , Peters Julius 
Published: January 2005

AbstractSubacute sclerosing panencephalitis (SSPE) is related to “defective” measles virus or vaccination, though an association with parainfluenza viruses has been reported. SSPE is characterized by a slow, erratic course and elevated cerebrospinal fluid measles titers. An immunocompetent, vaccinated infant, with onset of symptoms in parainfluenza virus season and a catastrophic course is described. Cerebrospinal fluid titers were negative, but postmortem brain had typical SSPE lesions. Patient brain‐derived RNA, subjected to reverse transcription followed by polymerase chain reaction yielded polymerase chain reaction products with measles virus but not parainfluenza virus genes. The sequenced fragment revealed multiple mutations, typical for SSPE. SSPE can thus present in infants, with short latency and no cerebrospinal fluid antibodies. Viral genomic analysis may be diagnostic, permitting early therapy.
Discordant twins with Parkinson's disease: Positron emission tomography and early signs of impaired cognitive circuits
Authors: Holthoff V. A. , Vieregge P. , Kessler J. , Pietrzyk U. , Herholz K. , Bönner J. , Wagner R. , Wienhard K. , Pawlik G. , Heiss W.‐D. 
Published: January 2005

AbstractWe evaluated 7 pairs of twins (2 monozygotic and 5 dizygotic) discordant for Parkinson's disease (PD), of whom the cotwins showed no signs of motor impairment on neurological examination. All subjects underwent positron emission tomographic measurements of cerebral glucose metabolism and dopaminergic, nigrostriatal function following injection of 2‐[18F]fluoro‐2‐deoxy‐D‐glucose and L‐6‐[18F]fluorodopa ([18F]dopa), respectively, as well as testing for anterograde, verbal episodic, and semantic memory performance. Statistical analysis demonstrated significant reduction of striatal [18F]dopa uptake not only in the twin patients with PD but also in all of the cotwins, who showed significantly (p < 0.05) impaired [18F]dopa metabolism in at least one of the striatal measures including caudate, putaminal, and the rostrocaudal putaminal gradient of [18F]dopa uptake. Compared with age‐matched controls, regional glucose metabolism was unchanged in all the twins. Neuropsychological testing showed significant (p < 0.05) 0.0(5) impairment in verbal memory processing in the twin patients with PD and in 6 of the cotwins. Semantic memory skills were affected in 2 twin patients only. A significant correlation was found between scores obtained in Buschke's Selective Reminding Test and striatal [18F]dopa uptake, further substantiating the role of dopaminergic pathways in memory processing. The present study is the first to reveal not only significant disturbance of nigrostriatal dopaminergic function in asymptomatic cotwins of twin patients with PD, but also significant impairment in the processing of anterograde, verbal episodic memory that is known to be affected in PD. Larger studies with a longitudinal design will be necessary to answer the question of whether cognitive changes found in the cotwin group are signs of incipient PD.
The effect of systemically administered recombinant human nerve growth factor in healthy human subjects
Authors: Petty Brent G. , Cornblath David R. , Adornato Bruce T. , Chaudhry Vinay , Flexner Charles , Wachsman Matthew , Sinicropi Dominick , Burton Louis E. , Peroutka Stephen J. 
Published: January 2005

AbstractThis phase I double‐masked, randomized, placebocontrolled study evaluated the safety of single intravenous or subcutaneous doses of recombinant human nerve growth factor (rhNGF) in healthy human volunteers at doses ranging from 0.03 to 1 μg/kg. No life‐threatening adverse events were seen at any dose. At doses above 0.1 μg/kg, subjects reported mild to moderate muscle pain, primarily in the bulbar and truncal musculature. The duration and severity of these myalgias varied in a dosedependent manner, and women appeared to be more susceptible than men. Intravenous rhNGF produced earlier and more pronounced systemic effects than did identical subcutaneous doses. Subjects receiving subcutaneous rhNGF noted hyperalgesia at the injection site, a local effect persisting up to 7 weeks, that also varied in a dose‐dependent manner. Antibodies to NGF were not detected in any subject. These results indicate that systemically administered rhNGF exerts a characteristic and reproducible biological effect in healthy subjects at very low doses and in a dose‐dependent manner.
Genetic linkage studies in autosomal dominant parkinsonism: Evaluation of seven candidate genes
Authors: Gasser T. , Wszolek Z. K. , Trofatter J. , Ozelius L. , Uitti R. J. , Lee C. S. , Gusella J. , Pfeiffer R. F. , Calne D. B. , Breakefield X. O. 
Published: January 2005

AbstractLinkage studies were performed in three families (A, B, and C) with autosomal dominantly inherited parkinsonism affecting multiple members in three generations. Affected individuals exhibited the cardinal signs and symptoms of Parkinson's disease, with a mean age of onset of 51, 62, and 61 years in Families A, B, and C, respectively. Parkinsonian symptoms responded to L‐dopa treatment, and an [18F]6‐fluoro‐L‐dopa positron emission tomography scan in 1 affected member of Family B showed decreased striatal uptake typical of Parkinson's disease. Ancestors of all three families were traced to a small region in northern Germany and southern Denmark, suggesting the possibility of a common mutation. Linkage studies were performed with polymorphic markers associated with the following candidate genes: the genes for glutathione peroxidase (GPX1, 3q11), tyrosine hydroxylase (TH, 11p15.5), brain‐derived neurotrophic factor (BDNF, 11p14), catalase (CAT, 11p13), amyloid precursor protein (APP, 21q21), copper‐zinc superoxide dismutase (SODI, 21q21), and debrisoquin 4‐hydroxylase (CYP2D6, 22q13.1). Summed lod scores for all families excluded linkage to the genes GPX1, TH, APP, SODI, and CYP2D6, as well as to the chromosomal region containing the genes CAT and BDNF. If families were analyzed individually, exclusion was possible for two (Family A), six (Family B), and five (Family C) of the seven candidate genes. There was strong evidence against linkage for the remaining loci in all families analyzed individually, except for TH, which was uninformative in Families A and B, and CYP2D6, which gave slightly positive pairwise lod scores in Family A. Our results indicate that the candidate genes investigated are not involved in the etiology of parkinsonism in these families.
Band heterotopia: Correlation of outcome with magnetic resonance imaging parameters
Authors: Barkovich A. J. , Guerrini R. , Battaglia G. , Kalifa G. , N'Guyen T. , Parmeggiani A. , Santucci M. , Giovanardi‐Rossi P. , Granata T. , D'Incerti L. 
Published: January 2005

AbstractThe “band heterotopia” or “double cortex” is a brain anomaly that is presumed to result from a premature arrest of neuronal migration. Patients with this anomaly are reported to have a variable clinical course that has been, heretofore, unpredictable. The clinical records and magnetic resonance (MR) imaging studies of 27 patients with band heterotopia were retrospectively reviewed in an attempt to determine whether imaging findings are useful in predicting clinical outcome of affected patients. Statistical analyses revealed the following corelations: (1) severity of T2 prolongation in the brain with motor delay (p = 0.03); (2) degree of ventricular enlargement with the age of seizure onset (p = 0.04) and with development and intelligence (p = 0.04); (3) severity of pachygyria with the age of seizure onset (p = 0.01), seizure type (p = 0.03), and an abnormal neurologic examination (p = 0.002); (4) parietal involvement with delayed speech development (p = 0.05); (5) occipital involvement with age of seizure onset (p = 0.006); (6) age of seizure onset with development and intelligence (p = 0.03) and with an abnormal neurologic examination (p = 0.04); and (7) severity of the pachygyria and thickness of band with development of symptomatic generalized epilepsy (p = 0.002 and p = 0.02, respectively) and Lennox‐Gastaut syndrome (p = 0.002 and p = 0.01, respectively).
Red nuclear and cerebellar but no olivary activation associated with essential tremor: A positron emission tomoraphic study
Authors: Wills A. J. , Jenkins I. H. , Thompson P. D. , Findley L. J. , Brooks D. J. 
Published: January 2005

AbstractThere has been debate as to whether essential tremor has a central origin and over the possible role of the inferior olivary nucleus in its genesis. We use positron emission tomography with radioactve water (H215O) to detect abnormal patterns of cerebral activity associated with this condition, at rest, without tremor, and on posture when the tremor was present. At rest, cerebellar blood flow was significantly increased bilaterally in the group with essential tremor (30–40%) but no increased olivary activity was evident. Essential tremor during arem extension was associated with further abnormal increases in bilateral cerebellar and abnormal red nuclear activation. Again, no olivary overactivity was evident. Voluntary wrist oscillation in control subjects caused only ipsilateral cerebellar activation. We conclude that essential tremor is associated with abnormal bilateral overactivity of cerebellar and red nuclear connections but found no evidence of intrinsic overactivity of the inferior olivary nucleus, as evidenced by raised blood flow.
Cytokine expression in the muscle of HIV‐infected patients: Evidence for interleukin‐1α accumulation in mitochondria of AZT fibers
Authors: Gherardi R. K. , Florea‐Strat A. , Fromont G. , Poron F. , Sabourin J‐C. , Authier J. 
Published: January 2005

AbstractTo evaluate the possible role of cytokines in human immunodeficiency virus (HIV)–associated muscular disorders, we performed immunocytochemistry for interleukin‐1α, ‐1β, and ‐6 and tumor necrosis factor‐α on frozen muscle biopsy specimens from HIV‐infected patients with various myopathies (HIV polymyositis in 5, HIV‐wasting syndrome in 5, zidovudine myopathy in 10) and from seronegative individuals (normal muscle in 2, mitochondrial cytopathies in 10). The HIV‐infected patients showed positive reactivities in vessels (interleukin‐1) and in inflammatory cells (mainly interleukin‐1 and tumor necrosis factor‐α), including perivascular hemosiderin‐laden macrophages in 5 patients. In zidovudine myopathy, a majority of AZT fibers (i.e., ragged‐red fibers with marked myofibrillar changes) showed mild to marked expression of interleukin‐1. Expression of interleukin‐1 in the other mitochondrial myopathies was much weaker. Interleukin‐1β messenger RNA was demonstrated in muscle fibers by in situ hybridization, implying that interleukin‐1 was produced in muscle cells. Immunoelectron microscopy showed that interleukin‐1α was mainly bound to mitochondrial membranes in AZT fibers. Proinflammatory and destructive effects of the studied cytokines might be responsible for several myopathological changes observed in HIV‐infected patients, including inflammation and hemosiderin deposits in muscle tissue, and prominent myofibrillar breakdown in AZT fibers.
Metabolic recovery in caudate nucleus of children following cerebral hemispherectomy
Authors: Chugani Harry T. , Jacobs Bob 
Published: January 2005

AbstractIn 3 children who had undergone cerebral hemispherectomy (hemidecortication) between the ages of 1 year 5 months and 4 years for the alleviation of intractable epilepsy, cerebral glucose utilization was studied serially with positron emission tomography. Three to 7 months after hemispherectomy, glucose utilization in the caudate nuclei on the side of hemispherectomy had decreased to below preoperative values, presumably due to total deprivation of ipsilateral cortical input. One to 2.5 years after surgery, complete restoration of glucose metabolic activity to preoperative levels was seen in 2 patients and partial recovery was seen in 1 patient. These alterations of cerebral glucose utilization are believed to reflect microscopic anatomical reorganizational changes (e.g., collateral sprouting) that have been documented following similar lesions in several animal models. Our findings suggest that positron emission tomography may provide a sensitive measure of developmental brain plasticity in vivo.
Complex I, Iron, and ferritin in Parkinson's disease substantia nigra
Authors: Mann V. M. , Cooper J. M. , Daniel S. E. , Srai K. , Jenner P. , Marsden C. D. , Schapira A. H. V. 
Published: January 2005

AbstractElevated iron levels, enhanced oxidative damage, and complex I deficiency have been identified in the substantia nigra of Parkinson's disease patients. To understand the interrelationship of these abnormalities, we analyzed iron levels, ferritin levels, and complex I activity in the substantia nigra of patients with Parkinson's disease. Total iron levels were increased significantly, ferritin levels were unchanged, and complex I activities were decreased significantly in the substantia nigra samples. The failure of ferritin levels to increase with elevated iron concentrations suggests that the amount of reactive iron may increase in the substantia nigra of Parkinson's disease patients. There was no correlation between the iron levels and complex I activity or the iron‐ferritin ratio and complex I activity in the substantia nigra samples.
Immunological and pathological study of anti‐Ri–associated encephalopathy
Authors: Hormigo Adialia , Dalmau Josep , Rosenblum Marc K. , River Mary E. , Posner Jerome B. 
Published: January 2005

AbstractA patient with high titers of the anti‐Ri antibody died 3 years after a progressive course with ataxia, opsoclonus, dementia, and peripheral neuropathy. At autopsy, no tumor was found. The nervous system exhibited severe Purkinje cell loss and contained perivascular and interstitial inflammatory infiltrates, particularly involving the brainstem. B and CD4 cells predominated in the perivascular spaces and CD8 cells in the interstitial infiltrates. Complement reactivity and natural killer cells were present and predominated in areas with more intense inflammatory infiltrates. Deposits of IgG were detected in the cytoplasm and nuclei of some neurons, particularly those in the brainstem tegmentum. The proportion of anti‐Ri IgG in the total IgG extracted from various areas of the brain, serum, and cerebrospinal fluid was determined by quantitative western blot analysis. Anti‐Ri reactivity was identified in immunoblots of all regions of the brain, but it predominated in basis pontis and dorsal mesencephalon. Our findings support the hypothesis of an autoimmune basis for the disorder and suggest that an antibody‐mediated mechanism may play a role in its pathogenesis.
Phenotypic heterogeneity of an adult form of adrenoleukodystrophy in monozygotic twins
Authors: Sobue Gen , Ueno‐Natsukari Ikuko , Okamoto Hideki , Connell Thomas A. , Aizawa Izumi , Mizoguchi Koichi , Honma Masamitsu , Ishikawa Gen , Mitsuma Terunori , Natsukari Naoki 
Published: January 2005

AbstractWe describe genetically proven monozygotic twins with the adult form of adrenoleukodystrophy with significant phenotypic heterogeneity. Myeloneuropathy was common to both patients, but cognitive impairment and affective symptoms with extensive demyelination in the brain were prominent in the older twin, while adrenal insufficiency was predominant in the younger twin. The younger twin, however, exhibited affective symptoms similar to those displayed by his elder twin 10 years later. These findings suggest that nongenetic factors are important in determining the phenotypic variation of adrenoleukodystrophy gene.