bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergy of insulin‐like growth factor‐1 and exercise in amyotrophic lateral sclerosis
Authors: Kaspar Brian K. , Frost Lindsay M. , Christian Lindsey , Umapathi Priya , Gage Fred H. 
Published: April 2005

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the neuromuscular system resulting in paralysis and ultimately death. Currently, no effective therapy is prescribed for patients; however, several therapeutic strategies are showing promise. Either exercise or treatment with adeno‐associated virus/insulin‐like growth factor–1 alone has therapeutic benefits in an amyotrophic lateral sclerosis transgenic mouse model. We show here that activity duration affects the therapeutic benefit associated with exercise, with 6‐ and 12‐hour exposure to a running wheel providing significant motor function benefits and increased survival. Remarkably, a combination of insulin‐like growth factor–1 gene delivery and exercise has profound effects on survival and function, indicative of synergistic effects with exercise and insulin‐like growth factor–1. Our results indicate that a drug treatment in combination with appropriate exercise may provide the most promising therapy for amyotrophic lateral sclerosis to date. Ann Neurol 2005
Acetylcholinesterase inhibitors reduce brain and blood interleukin‐1β production
Authors: Pollak Yehuda , Gilboa Adi , Ben‐Menachem Ofra , Ben‐Hur Tamir , Soreq Hermona , Yirmiya Raz 
Published: April 2005

AbstractOverproduction of interleukin‐1 within the brain is associated with Alzheimer's disease and other neurological conditions. We report that peripheral administration of the acetylcholinesterase inhibitors tacrine, rivastigmine, neostigmine, or EN101 (an antisense oligonucleotide directed at acetylcholinesterase messenger RNA) to mice significantly attenuated the production of interleukin‐1β in the hippocampus and blood, concomitantly with the reduction in acetylcholinesterase activity. These findings demonstrate that cholinergic enhancement produces central and peripheral antiinflammatory effects and suggest a novel therapeutic mechanism for acetylcholinesterase inhibitors. Ann Neurol 2005
Clinical features of LRRK2‐associated Parkinson's disease in central Norway
Authors: Aasly Jan O. , Toft Mathias , Fernandez‐Mata Ignacio , Kachergus Jennifer , Hulihan Mary , White Linda R. , Farrer Matthew 
Published: April 2005

AbstractSeveral pathogenic mutations in the leucine‐rich repeat kinase 2 (LRRK2; PARK8) gene recently have been identified in familial and sporadic parkinsonism. We screened 435 Norwegian patients diagnosed with Parkinson's disease and 519 control subjects for the presence of 7 LRRK2 mutations. Nine patients from seven families were found to be heterozygote carriers of the LRRK2 6055G>A (G2019S) mutation. Twelve of 28 first‐degree relatives also carried the mutation, but only 1 had Parkinson's disease. The clinical features included asymmetric resting tremor, bradykinesia, and rigidity with a good response to levodopa and could not be distinguished from idiopathic Parkinson's disease. Ann Neurol 2005;57:762–765
Pallidal stimulation improves pantothenate kinase–associated neurodegeneration
Authors: Castelnau Pierre , Cif Laura , Valente Enza Maria , Vayssiere Nathalie , Hemm Simone , Gannau Amandine , DiGiorgio Annalisa , Coubes Philippe 
Published: April 2005

AbstractPantothenate kinase–associated neurodegeneration (PKAN) causes a progressive generalized dystonia which remains pharmacologically intractable. We performed bilateral internal globus pallidus stimulation in six patients with genetically confirmed PKAN who obtained a major and long‐lasting improvement of their painful spasms, dystonia, and functional autonomy. This study shows the benefits of pallidal DBS for the dystonia of PKAN patients. Ann Neurol 2005;57:738–741
Effects of Cav3.2 channel mutations linked to idiopathic generalized epilepsy
Authors: Khosravani Houman , Bladen Christopher , Parker David B. , Snutch Terrance P. , McRory John E. , Zamponi Gerald W. 
Published: April 2005

AbstractHeron and colleagues (Ann Neurol 2004;55:595–596) identified three missense mutations in the Cav3.2 T‐type calcium channel gene (CACNA1H) in patients with idiopathic generalized epilepsy. None of the variants were associated with a specific epilepsy phenotype and were not found in patients with juvenile absence epilepsy or childhood absence epilepsy. Here, we introduced and functionally characterized these three mutations using transiently expressed human Cav3.2 channels. Two of the mutations exhibited functional changes that are consistent with increased channel function. Taken together, these findings along with previous reports, strongly implicate CACNA1H as a susceptibility gene in complex idiopathic generalized epilepsy. Ann Neurol 2005
Aerobic training in patients with myotonic dystrophy type 1
Authors: Ørngreen Mette C. , Olsen David B. , Vissing John 
Published: April 2005

AbstractThe effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing and muscle morphology before and after training. Patients increased their maximal oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter increased significantly, and creatine kinase did not increase with training. The study indicates that aerobic training is safe and can improve fitness effectively in patients with myotonic dystrophy. Ann Neurol 2005;57:754–757
Distal spinal and bulbar muscular atrophy caused by dynactin mutation
Authors: Puls Imke , Oh Shin J. , Sumner Charlotte J. , Wallace Karen E. , Floeter Mary Kay , Mann Eric A. , Kennedy William R. , Wendelschafer‐Crabb Gwen , Vortmeyer Alexander , Powers Richard , Finnegan Kimberly , Holzbaur Erika L. F. , Fischbeck Kenneth H. , Ludlow Christy L. 
Published: April 2005

AbstractImpaired axonal transport has been postulated to play a role in the pathophysiology of multiple neurodegenerative disorders. In this report, we describe the results of clinical and neuropathological studies in a family with an inherited form of motor neuron disease caused by mutation in the p150Glued subunit of dynactin, a microtubule motor protein essential for retrograde axonal transport. Affected family members had a distinct clinical phenotype characterized by early bilateral vocal fold paralysis affecting the adductor and abductor laryngeal muscles. They later experienced weakness and atrophy in the face, hands, and distal legs. The extremity involvement was greater in the hands than in the legs, and it had a particular predilection for the thenar muscles. No clinical or electrophysiological sensory abnormality existed; however, skin biopsy results showed morphological abnormalities of epidermal nerve fibers. An autopsy study of one patient showed motor neuron degeneration and axonal loss in the ventral horn of the spinal cord and hypoglossal nucleus of the medulla. Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a unique pattern of motor neuron degeneration that is associated with the accumulation of dynein and dynactin in neuronal inclusions. Ann Neurol 2005;57:687–694
Natural history of denervation in SMA: Relation to age, SMN2 copy number, and function
Authors: Swoboda Kathryn J. , Prior Thomas W. , Scott Charles B. , McNaught Teresa P. , Wride Mark C. , Reyna Sandra P. , Bromberg Mark B. 
Published: April 2005

AbstractDenervation was assessed in 89 spinal muscular atrophy (SMA) 1, 2, and 3 subjects via motor unit number estimation (MUNE) and maximum compound motor action potential amplitude (CMAP) studies, and results correlated with SMN2 copy, age, and function. MUNE and maximum CMAP values were distinct among SMA subtypes (p < 0.05). Changes in MUNE and maximum CMAP values over time were dependent on age, SMA type, and SMN2 copy number. SMN2 copy number less than 3 correlated with lower MUNE and maximum CMAP values (p < 0.0001) and worse functional outcomes. As SMN2 copy number increases, so does functional status (p < 0.0001). Change in MUNE longitudinally over the time intervals examined in this study was not statistically significant for any SMA cohort. However, a decline in maximum CMAP over time was apparent in SMA2 subjects (p = 0.049). Age‐dependent decline in MUNE and maximum CMAP was apparent in both SMA 1 (p < 0.0001) and SMA 2 (p < 0.0001) subjects, with age as an independent factor regardless of type. Maximum CMAP at the time of the initial assessment was most predictive of functional outcome (p < 0.0001). Prospective longitudinal studies in four prenatally diagnosed infants demonstrated significant progressive denervation in association with symptomatic onset or functional decline. These data highlight the potential value of such measures in increasing our understanding of pathophysiological factors involved in denervation in SMA. Ann Neurol 2005;57:704–712
Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications
Authors: Bubber Parvesh , Haroutunian Vahram , Fisch Gene , Blass John P. , Gibson Gary E. 
Published: April 2005

AbstractReductions in cerebral metabolism sufficient to impair cognition in normal individuals also occur in Alzheimer's disease (AD). The degree of clinical disability in AD correlates closely to the magnitude of the reduction in brain metabolism. Therefore, we tested whether impairments in tricarboxylic acid (TCA) cycle enzymes of mitochondria correlate with disability. Brains were from patients with autopsy‐confirmed AD and clinical dementia ratings (CDRs) before death. Significant (p < 0.01) decreases occurred in the activities of the pyruvate dehydrogenase complex (−41%), isocitrate dehydrogenase (−27%), and the α‐ketoglutarate dehydrogenase complex (−57%). Activities of succinate dehydrogenase (complex II) (+44%) and malate dehydrogenase (+54%) were increased (p < 0.01). Activities of the other four TCA cycle enzymes were unchanged. All of the changes in TCA cycle activities correlated with the clinical state (p < 0.01), suggesting a coordinated mitochondrial alteration. The highest correlation was with pyruvate dehydrogenase complex (r = 0.77, r2 = 0.59). Measures to improve TCA cycle metabolism might benefit AD patients. Ann Neurol 2005;57:695–703
Fruit and vegetable consumption and cognitive decline in aging women
Authors: Kang Jae H. , Ascherio Alberto , Grodstein Francine 
Published: April 2005

AbstractWe prospectively examined fruit and vegetable intake in relation to cognitive function and decline among aging women. Participants were followed from in 1976 with biennial questionnaires, and food frequency questionnaires were administered in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered, by telephone, six cognitive tests measuring general cognition, verbal memory, category fluency, and working memory. We repeated assessments two years later for 13,388 women (>90% follow‐up). We averaged dietary intakes from 1984 through the first cognitive assessment, and used linear regression to obtain multivariable‐adjusted mean differences in performance and decline in performance across intake levels. Fruits were not associated with cognition or cognitive decline. However, total vegetable intake was significantly associated with less decline. Specifically, on a global score combining all tests, women in the highest quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women consuming the most green leafy vegetables also experienced slower decline than women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02, 0.09; p trend < 0.001). These mean differences were equivalent to those observed for women about 1 to 2 years apart in age. Ann Neurol 2005;57:713–720
Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease
Authors: Grossman Murray , Farmer Jennifer , Leight Susan , Work Melissa , Moore Peachie , Van Deerlin Vivianna , Pratico Domenico , Clark Christopher M. , Coslett H. Branch , Chatterjee Anjan , Gee James , Trojanowski John Q. , Lee Virginia M.‐Y. 
Published: April 2005

AbstractWe assessed cerebrospinal fluid (CSF) levels of tau and other biomarkers of neurodegenerative disease. CSF tau levels vary widely in reports of frontotemporal dementia (FTD). CSF samples were assayed for tau, amyloid β1‐42 (A1‐42), and the isoprostane 8,12‐iso‐iPF2a‐VI (iP) prospectively in 64 patients with FTD, retrospectively in 26 autopsied cases with FTD or Alzheimer's disease (AD), and in 13 healthy seniors. To validate our observations in vivo, we correlated CSF tau levels with cortical atrophy in 17 FTD patients using voxel‐based morphometry analyses of high‐resolution magnetic resonance imaging. CSF levels of tau, Aβ1‐42, and iP differed significantly in FTD compared with AD. Individual patient analyses showed that 34% of FD patients had significantly low levels of CSF tau, although this was never seen in AD. A discriminant analysis based on CSF levels of tau, Aβ1‐42, and iP was able to classify 88.5% of these patients in a manner that corresponds to their clinical or autopsy diagnosis. Magnetic resonance imaging studies showed that CSF tau levels correlate significantly with right frontal and left temporal cortical atrophy, brain regions known to be atrophic in patients with autopsy‐proved FTD. We conclude that CSF tau levels are significantly reduced in many patients with FTD. Ann Neurol 2005;57:721–729
Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13
Authors: Macedo‐Souza Lucia I. , Kok Fernando , Santos Silvana , Amorim Simone C. , Starling Alessandra , Nishimura Agnes , Lezirovitz Karina , Lino Angelina M. M. , Zatz Mayana 
Published: April 2005

AbstractWe report an autosomal recessive neurodegenerative disorder in 25 white members from a large inbred Brazilian family, 22 of whom were evaluated clinically. This condition is characterized by (1) subnormal vision secondary to apparently nonprogressive congenital optic atrophy; (2) onset of progressive spastic paraplegia in infancy; (3) onset of progressive motor and sensory axonal neuropathy in late childhood/early adolescence; (4) dysarthria starting in the third decade of life; (5) exacerbated acoustic startle response; and (6) progressive joint contractures and spine deformities. Motor handicap was severe, and all patients were wheelchair bound after 15 years old. We performed a genome‐wide screen including 25 affected individuals and 49 of their unaffected relatives. Linkage was detected at 11q13 region with a maximum logarithm of odds score of +14.43, obtained with marker D11S1883. The candidate region, which lies between D11S1908 and D11S1889, encompasses ∼4.8Mb and has more than 100 genes and expressed sequences. We propose the acronym SPOAN (spastic paraplegia, optic atrophy, and neuropathy) for this complex syndrome. Ann Neurol 2005;57:730–737
Tumor necrosis factor‐α inhibits seizures in mice via p75 receptors
Authors: Balosso Silvia , Ravizza Teresa , Perego Carlo , Peschon Jacques , Campbell Iain L. , De Simoni Maria Grazia , Vezzani Annamaria 
Published: April 2005

AbstractBrain inflammatory reactions have been described in various neurological disorders, including epilepsy. Although there is clear evidence that cytokines affect neuroglial functions and blood–brain barrier permeability, scarce information is available on the functional consequences of brain inflammation on seizures. We studied the role of tumor necrosis factor‐α (TNF)‐α and its p55 and p75 receptors in seizure modulation. We found that intrahippocampal injection of murine recombinant TNF‐α potently inhibits seizure in mice while human recombinant TNF‐α, which shows strong specificity for mouse p55 receptors, was ineffective. p75 receptors were detected in mouse hippocampal neurons, whereas p55 receptors were absent. Transgenic mice with a perturbed TNF‐α system showed profound alterations in seizure susceptibility: astrocytic overexpression of TNF‐α was associated with reduced seizures, whereas mice lacking TNF‐α p75 or both p55 and p75, receptors showed prolonged seizures. Mice deficient in p55 receptor only showed reduced seizures; and both p75 and TNF receptor–associated factor 2 protein levels were upregulated in their hippocampi. Our findings show that increased brain levels of TNF‐α result in significant inhibition of seizures in mice, and this action is mediated by neuronal p75 receptors. This evidence highlights a novel function of TNF‐α in brain and indicates a new system for anticonvulsive intervention. Ann Neurol 2005
Overlap of pathology in paralytic rabies and axonal Guillain–Barré syndrome
Authors: Sheikh Kazim A. , Ramos‐Alvarez Manuel , Jackson Alan C. , Li Chun Y. , Asbury Arthur K. , Griffin John W. 
Published: April 2005

AbstractWe describe clinical and pathological features of a case of paralytic rabies with acute axonal neuropathy that closely resembled axonal Guillain–Barré syndrome. This case emphasizes that there is overlap of both clinical and pathological features in paralytic rabies and axonal Guillain–Barré syndrome. These findings raise the possibility that infectious and autoimmune etiologies can lead to similar morphological changes in the nerves. Ann Neurol 2005;57:768–772
Torsin A haplotype predisposes to idiopathic dystonia
Authors: Clarimon Jordi , Asgeirsson Hilmir , Singleton Andrew , Jakobsson Finnbogi , Hjaltason Haukur , Hardy John , Sveinbjornsdottir Sigurlaug 
Published: April 2005

AbstractPrevious work has suggested that in many neurological diseases genetic variability in the loci predisposing subjects to autosomal dominant disease contributes to the risk of sporadic disease. Here, using a population‐based sample of dystonia cases, we show an association with the torsin A haplotype and sporadic idiopathic dystonia. Ann Neurol 2005;57:765–767
Somatotopic organization of the corticospinal tract in the human brainstem: A MRI–based mapping analysis
Authors: Marx Juergen J. , Iannetti Gian D. , Thömke Frank , Fitzek Sabine , Urban Peter P. , Stoeter Peter , Cruccu Giorgio , Dieterich Marianne , Hopf Hanns C. 
Published: April 2005

AbstractTo investigate the incompletely understood somatotopical organization of the corticospinal tract in the human brainstem, we performed a voxel‐based statistical analysis of standardized magnetic resonance scans of 41 prospectively recruited patients with pyramidal tract dysfunction caused by acute brainstem infarction. Motor hemiparesis was rated clinically and by the investigation of motor evoked potentials to arms and legs. Infarction affected the pons in 85% of cases. We found the greatest level of significance of affected brainstem areas between the pontomesencephalic junction and the mid pons. Lesion location was significantly more dorsal in patients with hemiparesis affecting more proximal muscles and was significantly more ventral in patients with predominantly distal limb paresis. Comparison of magnetic resonance lesion from patients with paresis predominantly affecting arm or leg did not show significant topographical differences. We conclude that a topographical arm/leg distribution of corticospinal fibers is abruptly broken down as the descending corticospinal tract traverses the pons. Corticospinal fibers, however, follow a somatotopical order in the pons with fibers controlling proximal muscles being located close to the reticular formation in the dorsal pontine base, and thus more dorsal than the fibers controlling further distal muscle groups. Ann Neurol 2005
Experiments with the square array
Authors: Aspinall A. , Saunders M. K. 
Published: April 2005

AbstractElectrical resistance data were collected in an electrolytic tank, using the main configurations of the square array, in order to assess the behaviour of the system over an insulating sphere and prism. Experiments carried out were:

(i) mapping of area responses for targets at a fixed depth and the effect of strike direction and electrode separation on anomaly form;
(ii) production of pseudosections;
(iii) investigation of the depth response of the array at different electrode spacings.

Field tests were carried out on a selection of sites in the UK in order to examine the findings of the laboratory experiments. Copyright © 2005 John Wiley & Sons, Ltd.
Integrated interpretation of geophysical data in the archaeological site of Europos (northern Greece)
Authors: Diamanti N. G. , Tsokas G. N. , Tsourlos P. I. , Vafidis A. 
Published: April 2005

AbstractA multimethod geophysical survey was carried out in the archaeological site of Europos (northern Greece), to study the combined effectiveness and the merits of an integrated approach.Resistivity mapping was used to detect the shallower remains of the subsurface structures. Also, resistivity tomographies were carried out along dense profiles, to obtain further information on the vertical and lateral extent of the buried bodies. Two‐dimensional inversion of resistivity data was performed using the smoothness constrained and robust inversion schemes.The magnetic total and residual field maps of the area studied are presented. Two‐dimensional inversion of magnetic profiles was performed using the Levenberg–Marquadt method. The results of the magnetic data processing are in agreement with the anomalous zones that are revealed by the resistivity prospection.The results obtained by different methods assisted the interpretation of the three‐dimensional subsurface structures inferred by the resistivity tomographies.A comparison of the results of the applied surveying methods was made, checking for the relative merits and demerits of the different techniques. Their combination is discussed, in terms of providing enhanced views contradicting the use of a single method. Technical disadvantages of the multimethod approach are also pointed out. Copyright © 2005 John Wiley & Sons, Ltd.
Associating search and navigation behavior through log analysis
Authors: Mat‐Hassan Mazlita , Levene Mark 
Published: April 2005

AbstractWe report on a study that was undertaken to better understand search and navigation behavior by exploiting the close association between the process underlying users' query submission and the navigational trails emanating from query clickthroughs. To our knowledge, there has been little research towards bridging the gap between these two important processes pertaining to users' online information searching activity. Based on log data obtained from a search and navigation documentation system called AutoDoc, we propose a model of user search sessions and provide analysis on users' link or clickthrough selection behavior, reformulation activities, and search strategy patterns. We also conducted a simple user study to gauge users' perceptions of their information seeking activity when interacting with the system. The results obtained show that analyzing both the query submissions and navigation starting from query clickthrough, reveals much more interesting patterns than analyzing these two processes independently. On average, AutoDoc users submitted only one query per search session and entered approximately two query terms. Specifically, our results show how AutoDoc users are more inclined to submit new queries or resubmit modified queries than to navigate by link‐following. We also show that users' behavior within this search system can be approximated by Zipf's Law distribution.