bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive DNA deletion associated with severe disease alleles on spinal muscular atrophy homologues
Authors: Wang Ching H. , Carter Todd A. , Das Kamna , Xu Jin , Ross Barbara M. , Penchaszadeh Graciela K. , Gilliam T. Conrad 
Published: January 2005

AbstractSpinal muscular atrophy (SMA) is a motor neuron disease presenting with a wide spectrum of phenotypic variations. The primary cause of most, if not all, forms of childhood‐onset spinal muscular atrophy appears to be the homozygous loss of the telomeric copy of the survival motor neuron (SMNT) gene. It is interesting that approximately half of all affected patients are likewise homozygous nulls for the neuronal apoptosis inhibitory protein (NAIP) gene and a somewhat lessor fraction for the basal transcription factor, p44 subunit (BTFP44) gene. It has been proposed that homozygous loss of SMNT is the primary cause of spinal muscular atrophy while the loss of NAIP and perhaps other genes primarily affects the severity of disease manifestation. We explored this hypothesis by evaluating the extent of gene deletions in three multigenerational families with spinal muscular exhibiting dramatic intrafamilial phenotypic variation. Using somatic cell hybrid lines to sequester individual spinal muscular atrophy homologues, we show that homologues missing several contiguous genes correlate with “severe” disease alleles and homologues missing only SMNT correlate with “mild” disease alleles. These observations support the hypothesis that phenotypic severity among the childhood‐onset spinal muscular atrophies is directly correlated with the extent of disease‐specific deletions.
Circulating tumor necrosis factor‐α correlates with electrodiagnostic abnormalities in Guillain‐Barré syndrome
Authors: Sharief M. K. , Ingram D. A. , Swash M. 
Published: January 2005

AbstractAutoimmune damage to peripheral nerves, mediated by activated T lymphocytes and macrophages, underlies the pathogenesis of inflammatory demyelination in Guillain‐Barré syndrome. Both T lymphocytes and macrophages secrete tumor necrosis factor‐α, a cytokine that exerts toxic effects on myelin, Schwann cells, and endothelial cells. The reportedly high serum levels of this cytokine in patients with Guillain‐Barré syndrome may reflect the degree of immune activation rather than a direct pathogenic effect. We compared serum levels of tumor necrosis factor‐α, interleukin‐1β, and soluble interleukin‐2 receptor with well‐established electrodiagnostic criteria for primary demyelination in 23 patients with Guillain‐Barré syndrome, to assess the relationship between these cytokines and peripheral myelin damage. High serum levels of tumor necrosis factor‐α were associated with prolonged distal motor latencies and slowed motor conduction velocities, prolonged or absent F‐wave responses, and reduced amplitude of distal compound muscle action potentials. No significant correlation was observed between electrodiagnostic criteria for primary demyelination and serum levels of interleukin‐1β or soluble interleukin‐2 receptor. These findings suggest a putative role of tumor necrosis factor‐α in the pathogenesis of peripheral nerve demyelination in Guillain‐Barré syndrome.
Multiple sclerosis: Oligodendrocytes display cell death–related molecules in situ but do not undergo apoptosis
Authors: Bonetti Bruno , Raine Cedric S. 
Published: January 2005

AbstractTo investigate whether apoptosis is involved in the fate of oligodendrocytes in chronic multiple sclerosis lesions, the pro‐apoptotic molecules fas and tumor necrosis factor receptors and the anti‐apoptotic molecule bcl‐2 were examined by immunohistochemistry, and DNA fragmentation was assessed by an end labeling technique. Fas and both tumor necrosis factor receptors were preferentially expressed on oligodendrocytes in multiple sclerosis lesions, this phenotype being more evident at the lesion edge. The ligand for fasL, was constitutively present at high levels on microglia. The anti‐apoptotic molecule bcl‐2 was selectively expressed on oligodendrocytes in silent lesions and on astrocytes in active lesions. These molecules were also detected in control material, albeit at lower levels. In chronic active lesions, a few inflammatory cells displayed fas reactivity, whereas the majority expressed bcl‐2. DNA fragmentation was found in a number of infiltrating cells and some microglia, whereas, with one possible exception, oligodendrocytes showed no evidence of apoptosis. Thus, while apoptosis is involved in the elimination of infiltrating cells, it plays little or no role in oligodendrocyte depletion in multiple sclerosis, a process that may be related to a lytic pathway. In addition, microglia constitutively displayed the ligand for fas, and appeared to be the major effector cell population in the central nervous system.
Presenilin‐I polymorphism and hereditary cerebral hemorrhage with amyloidosis, Dutch type
Authors: Bornebroek M. , Haan J. , Backhovens H. , Deutz P. , Van Buchem M. A. , van den Broeck M. , Bakker E. , Roos R. A. C. , Van Broeckhoven C. 
Published: January 2005

AbstractHereditary cerebral hemorrhage with amyloidosis, Dutch type, caused by a mutation at codon 693 of the amyloid β precursor protein gene, is characterized by amyloid β deposition resulting in recurrent strokes and dementia. Recent data suggest that presenilin‐1 may be biologically linked to cerebral amyloid β deposition. The intronic presenilin‐1 polymorphism published by Wragg and colleagues (1996) was analyzed in 65 carriers of the hereditary cerebral hemorrhage with amylodosis, Dutch type, mutation. We found that the presenilin‐1 genotype was not correlated with age at first stroke, number of recurrences, dementia, and age at death or with white matter hyperintensities and focal lesions on magnetic resonance images. From our data we conclude that amyloid β deposition in this disease is most likely not influenced by presenilin‐1.
Familial spongiform encephalopathy associated with a novel prion protein gene mutation
Authors: Nitrini Ricardo , Rosemberg Sergio , Passos‐Bueno Maria Rita , da Silva Luís S. Teixeira , Iughetti Paula , Papadopoulos Maria , Carrilho Paulo M. , Caramelli Paulo , Albrecht Steffen , Zatz Mayana , LeBlanc Andrea 
Published: January 2005

AbstractHuman prion diseases include Creutzfeldt‐Jakob disease, Gerstmann‐Sträussler‐Scheinker disease, fatal familial insomnia, and kuru. Each of these diseases has a specific clinical presentation while spongiform encephalopathy, neuronal loss, and gliosis are their neuropathological hallmarks. We studied a Brazilian family with an autosomal dominant form of dementia. Nine members of the family were affected by a dementia with frontotemporal clinical features, with a mean age at onset of 44.8 ± 3.8 years and a mean duration of symptoms of 4.2 ± 2.4 years. Neuropathological examination of 3 patients showed severe spongiform change and neuronal loss in the deep cortical layers and in the putamen, but minimal gliosis in the most severely affected areas. The putamen and cerebellum, but not other areas of the affected brain, displayed prion protein immunoreactivity. A novel prion protein gene mutation causing a nonconservative substitution at codon 183 was identified in 2 neuropathologically confirmed affected individuals (mother and son). The mutation was transmitted in a mendelian fashion to 12 members of the family. Therefore, we identified a novel prion disease variant characterized by an early onset and long duration of the symptoms, severe spongiform change with minimal gliosis, associated with a prion protein gene mutation at codon 183.
Long‐duration response to levodopa influences the pharmacodynamics of short‐duration response in Parkinson's disease
Authors: Zappia Mario , Colao Rosanna , Montesanti Rita , Rizzo Milena , Aguglia Umberto , Gambardella Antonio , Oliveri Rosario Lćno , Quattrone Aldo 
Published: January 2005

AbstractThe long duration response (LDR) to chronic levodopa treatment may mask the short‐duration response (SDR) to a single dose of the drug in Parkinson's disease (PD). As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients. To evaluate the possible contamination of SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to a single dose of levodopa administered after a prolonged washout from chronic therapy and after a 15‐day treatment period with levodopa. Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout. Moreover, after treatment, SDR did not vary between patients with mild and severe PD, whereas, after washout, severely affected patients had larger but shorter SDR than mildly affected patients. The evaluation of SDR without the interference of LDR is critical in defining the characteristics of the therapeutic response to levodopa.
High‐frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor
Authors: Koller William , Pahwa Rajesh , Busenbark Karen , Hubble Jean , Wilkinson Steve , Lang Anthony , Tuite Paul , Sime Elspeth , Lazano Andres , Hauser Robert , Malapira Teresita , Smith Donald , Tarsy Daniel , Miyawaki Edison , Norregaard Thorkild , Kormos Theresa , Olanow C. Warren 
Published: January 2005

AbstractPharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high‐frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1‐year follow‐up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high‐frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.
The X‐linked infantile spasms syndrome (Mim 308350) maps to Xp 11.4–Xpter in two pedigrees
Authors: Claes S. , Devriendt K. , Lagae L. , Ceulemans B. , Dom L. , Casaer P. , Raeymaekers P. , Cassiman J. J. , Fryns J. P. 
Published: January 2005

AbstractWe report 2 families with X‐linked infantile spasms syndrome (X‐linked West syndrome). Data from clinical examination, biochemical analysis, neuroimaging, and neuropathology are discussed. In these families, genetic linkage analysis was able to locate the disease gene to the distal part of the short arm of the X chromosome, between Xpter and Xp11.4. This is the first report of linkage with genetic markers in this disorder. Although most cases are sporadic, further unraveling of the genetic background of the familial cases might greatly improve our understanding of infantile spasms.
Human immunodeficiency virus infection of dorsal root ganglion neurons detected by polymerase chain reaction in situ hybridization
Authors: Brannagan Thomas H. , Nuovo Gerard J. , Hays Arthur P. , Latov Norman 
Published: January 2005

AbstractA predominantly sensory peripheral neuropathy is common with human immunodeficiency virus (HIV) infection, but the cause is unknown. Formalin‐fixed dorsal root ganglia (DRG), obtained at postmortem from patients with neuropathy and HIV infection and from control subjects, were examined for the presence of HIV DNA by using polymerase chain reaction (PCR)‐amplified in situ hybridization. Viral message RNA was detected using reverse transcription in situ PCR with gag‐specific primers. HIV DNA and RNA sequences were detected in many satellite cells, mononuclear cells, and occasional neurons in 5 of 5 patients with HIV and neuropathy. HIV DNA was detected only in rare interstitial and satellite cells from 3 of 4 patients with HIV infection without neuropathy and was not detected in 6 patients without HIV infection. HIV infection of DRG neurons and supporting cells may contribute to the HIV‐associated sensory neuropathy.
A Bcl‐2 antisense oligonucleotide increases α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) toxicity in cortical cultures
Authors: White Melissa J. , Chen Jun , Li Zhu R. , Irvin Stacy , Sinor Amy , DiCaprio Michael J. , Jin Kunlin , Greenberg David A. 
Published: January 2005

AbstractBoth α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptor–mediated neurotoxicity and the induction of death‐regulatory genes have been implicated in the pathophysiology of delayed ischemic neuronal injury. To assess the role of the antiapoptotic gene Bcl‐2 in the modulation of AMPA toxicity, we exposed neuron‐enriched cultures from rat cerebral cortex to AMPA, in the absence or presence of an antisense oligodeoxynucleotide (ODN) directed against Bcl‐2. AMPA produced concentration‐dependent toxicity detected by a decrease in fluorescence of the redox indicator Alamar blue and by an increase in lactic acid dehydrogenase release. This effect was accompained by the induction of Bcl‐2 protein expression, with maximal induction at 100 μM AMPA. A phosphorothioate antisense ODN against Bcl‐2 reduced the AMPA‐stimulated induction of Bcl‐2 protein levels, detected by western blotting, by about 70%. In the presence of the antisense ODN, but not sense or scrambled ODNs, the toxicity of 100 μM AMPA was increased by about 60%. These findings suggest that induction of Bcl‐2 expression by AMPA may have a protective role to limit AMPA receptor–mediated neuronal damage and that modifying Bcl‐2 expression could have therapeutic potential in ischemia.
Pallidotomy for hemiballismus: Efficacy and characteristics of neuronal activity
Authors: Suarez J. I. , Metman L. Verhagen , Reich S. G. , Dougherty P. M. , Hallet M. , Lenz F. A. 
Published: January 2005

AbstractA patient with unremitting, medically intractable hemiballismus underwent a pallidotomy that abolished his involuntary movements. Firing rates of cells in the internal segment of the globus pallidus (GPi) recorded during this procedure were significantly lower than those observed during pallidotomy for Parkinson's disease, either “on” or “off” medication. Firing patterns in hemiballismus were characterized by low‐frequency modulation of the firing rate. These results are consistent with the hyperkinetic model, which suggests that hemiballismus results from decreased inhibition of the pallidal relay nucleus of the thalamus by the GPi. The efficacy of surgery in the case of hemiballismus demonstrates that pallidotomy can be an effective treatment for this condition and suggests that patterned neuronal activity in the GPi is important in the mechanism of hyperkinetic disorders.
Outcome after temporal lobectomy in bilateral temporal lobe epilepsy
Authors: Sirven Joseph I. , Malamut Barbara L. , Liporace Joyce D. , O'Connor Michael J. , Sperling Michael R. , O'Connor Michael J. 
Published: January 2005

AbstractWe determined how noninvasive presurgical data relate to prognosis after temporal lobectomy in patients with independent bilateral temporal lobe (IBTL) complex partial seizures on the intracranial electroencephalogram (EEG). Between 1986 and 1994, 28 patients had IBTL seizures on intracranial EEG. Fifteen of these 28 patients underwent temporal lobectomy and 13 were not offered surgery. Of the 15 patients who had surgery, 10 patients became seizure‐free. Magnetic resonance imaging (MRI) and the Wada test were the only variables associated with a seizure‐free outcome. Seven of 10 seizure‐free patients had a lateralized Wada result or the presence of unilateral hippocampal sclerosis, whereas none of the patients with persistent seizures had either of these findings. Variables not found to be predictive of a seizure‐free outcome included location of scalp interictal spikes, degree of seizure‐onset laterality, presence of early epilepsy risk factor, duration of epilepsy, and full‐scale intelligence quotient. We conclude that MRI and the Wada test provide information of prognostic value in patients with bilateral temporal seizures independent of intracranial EEG data.
Unilateral cerebellar lesions affect initiation of ipsilateral smooth pursuit eye movements in humans
Authors: Straube A. , Scheuerer W. , Eggert T. 
Published: January 2005

AbstractTo clarify the role of the cerebellum in pursuit initiation (first 100 msec), we used infrared oculography to examine the effect of unilateral cerebellar lessions on the initial (0–20 msec) and later (80–100 msec) periods as well as the steady‐state response (200–300 msec) of horizontal smooth pursuit in 10 patients with unilateral cerebellar lesions. These results were compared with those of 17 age‐matched healthy subjects. Smooth pursuit was elicited with a step‐ramp target movement with randomized horizontal directions and velocities of 10/sec and 30/sec. In the first 20‐msec pursuit, velocity was 22% lower toward the side of the cerebellar lesion than away from it and 16% lower in the period 80 to 100 msec (normal differences, 2% and 3%). Later (200–300 msec), the ipsiversive/contraversive difference was smaller, but pursuit velocity in both directions was significantly lower in patients than in normals. No lesion affected the floccular region and/or the nodulus/uvula. Five lesions extended so far medially that they could have affected the medial deep cerebellar nucleus (fastigial nucleus). The remaining five were in the lateral hemisphere in areas previously considered uninvolved in pursuit generation. Our findings prove that the cerebellum participates in human pursuit initiation and that lesions in the lateral cerebellum possibly affect smooth puröit.
Butyrylcholinesterase in the life cycle of amyloid plaques
Authors: Guillozet A. L. , Mesulam M.‐M. , Smiley J. F. , Mash D. C. 
Published: January 2005

AbstractDeposits of diffuse β‐amyloid (Aβ) may exist in the brain for many years before leading to neuritic degeneration and dementia. The factors that contribute to the putative transformation of the Aβ amyloid from a relatively inert to a pathogenic state remain unknown and may involve interactions with additional plaque consituents. Matching brain sections from 2 demented and 4 nondemented subjects were processed for the demonstration of Aβ immunoreactivity, butyrylchlinesterase (BChE) enzyme activity, and thioflavine S binding. Additional sections were processed for the concurrent demonstration of two or three of these markers. A comparative analysis of multiple cytoarchitectonic areas processed with each of these markers indicated that Aβ plaque deposits are likely to undergo three stages of maturation, ie, a “diffuse” thioflavine S–negative stage, a thioflavine S–positive (ie, compact) but nonneuritic stage, and a compact neuritic stage. A multiregional analysis showed that BChE‐positive plaques were not found in cytoarchitectonic areas or cortical layers that contained only the thioflavine S–negative, diffuse type of Aβ plaques. The BChE‐positive plaques were found only in areas containing thioflavine S–positive compact plaques, both neuritic and nonneuritic. Within such areas, almost all ( > 98%) BChE‐containing plaques bound thioflavine S, and almost all (93%) thioflavine S plaques contained BChE. These results suggest that BChE becomes associated with amyloid plaques at approximately the same time that the Aβ deposit assumes a compact β‐pleated conformation. BChE may therefore participate in the transformation of Aβ from an initially benign form to an eventually malignant form associated with neuritic tissue degeneration and clinical dementia.
Treatment of gustatory sweating with botulinum toxin
Authors: Toyka Klaus V. , Reiners Karlheinz , Naumann Markus , Zellner Max 
Published: January 2005

AbstractGustatory sweating is an autonomic disorder that frequently occurs after parotid gland surgery. We investigated the action of intracutaneous injections of botulinum toxin (BTX) (1.0–2.0 mouse units/2.25‐cm2 skin area) in 45 patients (mean age, 52 years) with gustatory sweating. The area of hyperhidrosis was determined by Minor's iodine test before and up to 24 weeks after the injection. The effect of BTX was assessed by measuring the hyperhidrotic area. The maximum BTX‐induced reduction of gustatory sweating was seen at 7.4 · 4.5 days after injection. The area of sweating decreased from 17.6 · 8.6 cm2 before BTX to 1.3 · 1.6 cm2 after BTX (p < 0.0001). Half the patients rated gustatory sweating subjectively as completely abolished, and the remainder felt pronounced improvement. No toxic effects were observed. In none of the patients did hyperhidrosis recur over a 6‐month follow‐up. We conclude that BTX is a safe and effective treatment that can be recommended as the therapy of choice in gustatory sweating.
Are portable folding chairs useful to combat orthostatic hypotension?
Authors: Smit Adrianus A. J. , Hardjowijono Mireille A. , Wieling Wouter 
Published: January 2005

AbstractThe effect of sitting on a derby chair (height, 48 cm), fishing chair (38 cm), and footstool (20 cm) on the improvement of postural hypotension was studied serially in 8 patients with autonomic failure. The increment in blood pressure during sitting was higher by using a lower portable chair. This was related to an increasing cardiac output at lower sitting heights. The fishing chair was, according to our patients' experience, most useful.
Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis
Authors: Filippi M. , Horsfield M. A. , Adèr H. J. , Barkhof F. , Bruzzi P. , Evans A. , Frank J. A. , Grossman R. I. , McFarland H. F. , Molyneux P. , Paty D. W. , Simon J. , Tofts P. S. , Wolinsky J. S. , Miller D. H. 
Published: January 2005

AbstractThe change of brain lesion load, measured on T2‐weighted magnetic resonance imaging (MRI) using computer‐assisted techniques, is a widely used secondary endpoint for phase III clinical trials in multiple sclerosis (MS). Collections, transfer, and analysis of the electronic data across multiple centers have all proved challenging and give rise to potential errors. However, many new acquisition schemes and postprocessing techniques have been developed; these may reduce scan times and result in better lesion conspicuity or lessen the human interaction needed for data analysis. This review considers many aspects of the use of MRI in clinical trials for MS and provides international consensus guidelines, derived from a task force of the European Magnetic Resonance Networks in Multiple Sclerosis (MAGNIMS) together with a group of North American experts. The main points considered are the organization of correctly powered trials and selection of participating sites; the appropriate choice of pulse sequences and image acquisition protocol given the current state of technology; quality assurance for data acquisition and analysis; accuracy and reproducibility of lesion load assessments; and the potential for the application of quantitative methods to other MRI‐derived measures of disease burden.