bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interical spiking increases 2‐deoxy[14C]glucose uptake and c‐fos—like reacitivity
Authors: Handforth Adrian , Finch David M. , Peters Richard , Tan Aiko M. , Treiman David M. 
Published: January 2005

AbstractAlthough interical spikes are thought to share pathophysiological mechanisms with partial‐onset seizure discharges, positron emission tomographic studies of the interictal stare have paradoxically shown focal hypometabolism whereas seizures produce hypermetabolism. To address this question, we performed functional mapping studies in an interictal spiking model in the rat. Recording screw electrodes were inserted through the skull bone so as to depress underlying cortex. Interictal spiking was subsequently induced by systemic administration of bicuculline methiodide. 2‐deoxy[14C]glucose studies revealed increased glucose utilization in superficial and middle cortical layers at spiking screw sites. Nonspiking screw sites in the same animals and in controls did not show increased uptake. Convulsive seizures caused additional 2‐deoxy[14C]glucose uptake at screw sites and in widespread forebrain areas. c‐fos immunoreactivity occurred in superficial cortex at interictal spiking, but not nonspiking, sites. Convulsive seizures induced widespread forebrain c‐fos immunoreactivity. These data suggest interictal epileptiform activity occurs in cells adjacent to cortical injury; these activate deeper layers via local connections. Interictal and ictal epileptiform states share common mechanisms, as both induce glucose hypermetabolism and immediate‐early gene product activation. Possible reasons for failure to detect hypermetabolism in interictal human subjects are discussed.
Neuropeptides in the sympathetic system: Presence, plasticity, modulation, and implications
Authors: Benarroch Eduardo E. 
Published: January 2005

AbstractNeuropeptides are ubiquitous in the sympathetic system and modulate transmission at the levels of the intermediolateral cell column, sympathetic ganglia, and neuroeffector junctions. Several neuropeptide‐containing pathways from the hypothalamus and medulla modulate excitability of preganglionic neurons. Neuropeptides coexist with norepinephrine or acetylcholine in subpopulations of chemically coded, target‐specific sympathetic ganglion neurons. Neuropeptide Y is colocalized in adrenergic vasconstrictor neurons, whereas vasoactive intestinal polypeptide is colocalized in cholinergic sudomotor neurons. Neuropeptide expression is plastic; during development, neurons that switch from a noradrenergic to a cholinergic phenotype increase expression of vasoactive intestinal polypeptide, somatostatin, and substance P. Preganglionic inputs increase neuropeptide Y and inhibit substance P expression. Sympathetic denervation produces sprouting of sensory fibers containing substance P and calcitonin gene–related peptide in target tissues. Neuropeptides from preganglionic fibers (e.g., enkephalin) and primary afferents (e.g., substance P, vasoactive intestinal polypeptide) modulate transmission in sympathetic ganglia. Neuropeptide Y produces vasoconstrction, prejunctional inhibition of norepinephrine release, and postjunctional potentiation of norepinephrine effects. Plasma neuropeptide Y increase during intense sympathoexcitation, hypertension, and pheochromocytoma. Dystrophic neurites containing neuropeptide Y occur in human sympathetic ganglia during aging, diabetes, and dysautonomia. Sympathetic neuropeptides may thus have important clinical implications.
Treatment of abnormal eye movements that impair vision: Strategies based on current concepts of physiology and pharmacology
Authors: Leigh R. John , Averbuch‐Heller Lea , Tomsak Robert L. , Remler Bernd F. , Yaniglos Stacy S. , Dell'Osso Louis F. 
Published: January 2005

AbstractCertain abnormal eye movements, especially pathological nystagmus, degrade vision and cause illusory motion of the seen environment. These symptoms are due to excessive movement of images of stationary objects on the retina. Recently, the pathophysiology underlying several types of nystagmus and saccadic oscillations was better defined by the development of animal models and by experimental pharmacological studies. Despite this, few reliable therapies are currently available for these abnormal eye movements. In clinical studies, a number of drugs reportedly helped individual patients, but few drugs have been subjected to double‐blind trials. An alternative approach to pharmacological suppression of abnormal eye movements is optical stabilization of images on the retina, which is helpful in selected patients. Weakening of the extraocular muscles, using botulinum toxin or surgery, is prone to cause diplopia and may induce plastic‐adaptive changes that render the effect temporary. In some patients, treatment of an underlying condition, such as the Arnold‐Chiari malformation, reduces nystagmus and improves vision. There is a need for multicenter trials to evaluate systematically potential treatments of abnormal eye movements that impair vision.
Biochemical alterations in multiple sclerosis lesions and normal‐appearing white matter detected by in vivo 31P and 1H spectroscopic imaging
Authors: Husted C. A. , Goodin D. S. , Hugg J. W. , Maudsley A. A. , Tsuruda J. S. , de Bie S. H. , Fein G. , Matson G. B. , Weiner M. W. 
Published: January 2005

AbstractThe goals of the current study were threefold: first, to confirm previous single volume proton (1H) magnetic resonance spectroscopy results of reduced N‐acetyl aspartate (NAA, a putative marker of neurons) in multiple sclerosis (MS) white matter lesions using multiple volume 1H magnetic resonance spectroscopic imaging (MRSI); second, to measure the phospholipid metabolites phosphomonoesters and phosphodiesters in such lesions using phosphorus (31P) MRSI; and third, to test the hypothesis that biochemical changes occur in the normal‐appearing (on spin echo T2‐weighted magnetic resonance images) white matter in patients with MS. Thirteen subjects with clinically definite MS were studied with both 1H and 31P MRSI, and 19 controls were studied with either 1H MRSI, 31P MRSI, or both. MS lesion, MS normal‐appearing white matter, and region‐matched control spectra from the centrum semiovale were analyzed. The major findings of this study were that in both white matter lesions and normal‐appearing white matter in patients with MS, the metabolite ratio NAA/creatine and the total 31P peak integrals were significantly reduced compared with controls. In addition, in MS lesions NAA/choline and phosphodiesters/total 31P were significantly reduced compared with controls, and in MS normal‐appearing white matter there was a trend for NAA/choline to be reduced compared with controls. In normal‐appearing white matter in patients with MS, total creatine and phosphocreatine were significantly increased compared to controls, as detected with both 1H (total creatine peak integrals) and 31P (phosphocreatine/total 31P) MRSI techniques. These results suggest reduced neuronal density and altered phospholipid metabolites in white matter lesions in patients with MS. Furthermore, the results suggest the presence of biochemical abnormalities not detected by standard spin echo magnetic resonance imaging in normal‐appearing white matter in MS.
Role of nerve growth factor in suramin neurotoxicity studied in vitro
Authors: Russell James W. , Windebank Anthony J. , Podratz Jewel L. 
Published: January 2005

AbstractWe determined whether suramin neurotoxicity can be prevented by nerve growth factor (NGF) and if this interaction occurs at the level of the NGF receptor. Neurite outgrowth from rat dorsal root ganglia in vitro was measured serially in the presence of suramin (100–600 μM) alone or with β‐NGF (50–1,000 ng/ml). Competitive NGF receptor–binding studies were done with 125I‐labeled NGF in the presence or absence of suramin. Neurite growth was inhibited in a dose‐dependent manner, but at usual neurotoxic levels this inhibition could be overcome completely by increasing the concentration of NGF. Receptor‐binding assays showed similar dose‐dependent inhibition of 125I‐labeled NGF binding. In the presence of suramin, the dissociation constant for high‐affinity binding was decreased from 1.2 × 10−11 to 3.9 × 10−10 and low‐affinity binding from 2.7 × 10−9 to 1.2 × 10−8. Increasing doses of suramin inhibited 125I‐labeled NGF specific binding in a dose‐dependent fashion, and doses of suramin ± 1,000 μM were able to completely inhibit 125I‐labeled NGF specific binding. Suramin‐induced dorsal root ganglia damage can be ameliorated by high‐dose NGF. This effect is most likely due to competition between suramin and NGF at the high‐affinity NGF receptor.
Phenobarbital modifies seizure‐related brain injury in the developing brain
Authors: Mikati Mohamad A. , Holmes Gregory L. , Chronopoulos Antonia , Hyde Pamela , Thurber Samuel , Gatt Arkadi , Liu Zhao , Werner Suzanne , Stafstrom Carl E. 
Published: January 2005

AbstractTo investigate the potential role of drug therapy in preventing or exacerbating seizure‐related brain injury in the prepubescent brain, we administered kainic acid to rats at postnatal day 35. Therapy with daily phenobarbital was started directly before or 1 day after kainic acid was administered, and was continued through postnatal day 153. Rats receiving phenobarbital had therapeutic concentrations during most of the 24‐hour dosing period, but also experienced supratherapeutic peak concentrations. The animals were subsequently tested using the water maze (a measure of visuospatial memory), open field (a measure of activity level), and handling tests (a measure of emotionality). The frequency of spontaneous recurrent seizures was monitored during and after phenobarbital therapy. Kainic acid resulted in status epilepticus on postnatal day 35 in all the rats that received it but those receiving phenobarbital first manifested a shorter and less severe status epilepticus as compared to the rats given kainic acid alone. Rats starting phenobarbital immediately before kainic acid was administered did not differ from control rats on behavioral testing and had no subsequent spontaneous recurrent seizures and no histological lesions. Rats receiving kainic acid alone performed significantly poorer than did control rats in the water maze, were more aggressive, had histological lesions, and manifested spontaneous recurrent seizures. As compared to the group treated only with kainic acid, rats receiving kainic acid followed by phenobarbital at postnatal days 36 to 153 manifested similar aggressiveness and histological lesions, similar frequency of spontaneous recurrent seizures after phenobarbital taper, and even greater disturbances in memory, learning, and activity level. These results demonstrate that kainic acid–related injury can be prevented by a medication working through inhibitory mechanisms; that structural and functional damage in the prepubescent brain can be prevented through strategically timed pharmacotherapy; and that treatment of spontaneous recurrent seizures alone with daily exposure to phenobarbital does not decrease, and may actually exacerbate, damage in the kainic acid model.
Trinucleotide repeat expansion in neurological disease
Authors: La Spada Albert R. , Paulson Henry L. , Fischbeck Kenneth H. 
Published: January 2005

AbstractExpansion of trincleotide repeats is now recognized as a major cause of neurological disease. At least seven disorders result from trinucleotide repeat expansion: X‐linked spinal and bulbar muscular atrophy (SBMA), two fragile×syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral‐pallidoluysian atrophy (DRPLA). The expanded trinucleotide repeats are unstable, and the phenomenon of anticipation, i.e., worsening of disease phenotype over successive generations, correlates with increasing expansion size. In this review, we compare the clinical and molecular features of the trinucleotide repeat diseases, which may be classified into two types. Fragile×and myotonic dystrophy are multisystem disorders usually associated with large expansions of untranslated repeats, while the four neurodegenerative disorders, SBMA, Huntington's disease, SCA1, and DRPLA, are caused by smaller expansions of CAG repeats within the protein coding portion of the gene. CAG repeats encode polyglutamine tracts. Polyglutamine tract expansion thus appears to be a common mechanism of inherited neurodegenerative disease. Although polyglutamine tract lenghthening presumably has a toxic gain of function effect in the CAG trinucleotide repeat disorders, the basis of this neuronal toxicity remains unknown.
Predictive value of apolipoprotein E genotyping in Alzheimer's disease: Results of an autopsy series and an analysis of several combined studies
Authors: Nalbantoglu Josephine , Gilfix Brian M. , Bertrand Philippe , Robitaille Yves , Gauthier Serge , Rosenblatt David S. , Poirier Judes 
Published: January 2005

AbstractApoliprotein E (apoE) is associated with Alzheimer's neurofibrillary tangles and β‐amyloid protein in senile plaques. Recent studies have shown an increased frequency of the ϵ4 allele of the apoE gene in familial and sporadic cases of Alzheimer's disease (AD). In the present case control study, we have determined the apoE genotype by allele‐specific extension of 113 postmortem cases of sporadic AD and 77 control brains shown to be free of AD neuropathological features and then calculated the frequency of the various allelic forms of apoE (ϵ2, ϵ3,ϵ4). The odds ratio associating ϵ4 with AD was 15.5 (95% confidence interval {CI} 6.2–38.5), and the population attributable risk was 0.53. We have also combined the results of our study and several others to calculate these same parameters in a larger population (570 controls and 961 AD subjects); the odds ratio for this larger group was 6.2 (95% CI 4.9–7.8) and the population attributable risk was 0.57. These results further substantiate and strengthen the association between the ϵ4 allele of apoE gene and AD. We have also used these results to investigate the usefulness of the determination of ϵ4 carrier status in the diagnosis of AD.
Low‐dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis
Authors: Goodkin Donald E. , Rudick Richard A. , Medendorp Sharon Vanderbrug , Daughtry Michele M. , Schwetz Kathleen M. , Fischer Jill , van Dyke Carolyn 
Published: January 2005

AbstractA randomized, double‐blinded, placebo‐controlled, clinical trial of low‐dose, weekly, oral methotrexate was performed in 60 patients with clinically definite chronic progressive multiple sclerosis (MS) attending a referral‐based outpatient MS clinic. Study patients were 21 to 60 years old with a disease duration of longer than 1 year. Patients' Expanded Disability Status Scale scores were 3.0 to 6.5 (ambulatory with moderate disability). Patients were first stratified by Expanded Disability Status Scale scores, 3.0 to 5.5 and 6.0 to 6.5, and then were randomized to receive methotrexate or placebo treatment. Treatment consisted of weekly, oral, low‐dose (7.5 mg) methotrexate or identical placebo for 2 years, followed by observation for as long as 1 year. A composite outcome measurement instrument was used and consisted of (1) Expanded Disability Status Scale, (2) ambulation index, (3) Box and Block Test, and (4) 9‐Hole Peg Test. Failure of therapy was indicated by a designated change that was sustained for more than 2 months in one or more components of this composite measure. Significantly less progression of impairment as measured by validated tests of upper‐extremity function was observed in the methotrexate treatment group in the absence of clinically significant toxicity. We conclude that low‐dose, weekly, oral methotrexate offers a new, relatively nontoxic treatment option for patients with chronic progressive MS.
Neuroprotective effects of gangliosides may involve inhibition of nitric oxide synthase
Authors: Dawson Ted M. , Hung Kenneth , Dawson Valina L. , Steiner Joseph P. , Snyder Solomon H. 
Published: January 2005

AbstractGangliosides are polar, sugar‐containing lipids that are major constituents of neuronal membranes. Gangliosides are neuroprotective in animal models of neurotoxicity and may also be useful in patients with clinical conditions such as spinal cord injury. We show that a series of gangliosides inhibit nitric oxide synthase activity by binding calmodulin. The prevention of glutamate neurotoxicity in cortical cultures by gangliosides closely parallels their potencies in binding calmodulin and inhibiting nitric oxide synthase. Neuroprotective effects of gangliosides may arise from blockade of nitric oxide formation.
Apolipoprotein E genotypes and Alzheimer's disease in a community study of elderly African Americans
Authors: Hendrie H. C. , Hall K. S. , Hui S. , Unverzagt F. W. , Yu C. E. , Lahiri D. K. , Sahota A. , Farlow M. , Musick B. , Brashear A. , Burdine V. E. , Osuntokun B. O. , Ogunniyi A. O. , Gureje O. , Baiyewu O. , Schellenberg G. D. 
Published: January 2005

AbstractAs part of a community‐based study of Alzheimer's disease (AD) in the African‐American population age 65 and over, we have determined apolipoprotein E (Apo E) genotypes in 85 subjects (31 AD patients and 54 controls). The €4 allele of Apo E was strongly associated with AD in this population sample. The € allele frequency in AD patients was 40.3% compared with 13.9% in the control group, and 22.6% of the AD patients were homozygous for this allele compared with 3.7% of the control subjects (p = 0.01). This study extends the association of Apo E‐∈4 and AD to nonwhite populations and provides further evidence that the observed allelic association is biologically relevant.
Changes in excitability of motor cortical circuitry in patients with parkinson's disease
Authors: Ridding M. C. , Rothwell J. C. , Inzelberg R. 
Published: January 2005

AbstractUsing the technique of transcranial magnetic stimulation over the motor areas of cortex and recording electromyographic (EMG) responses from the first dorsal interosseous muscle, we measured the excitability of corticocortical inhibitory circuits at rest using a double pulse paradigm, in 11 patients with Parkinson's disease (PD) studied both on (ON) and off (OFF) (after overnight withdrawal) their normal medication and in 10 age‐matched control subjects. There was a significant decrease in the amount of corticocortical inhibition at short (1–5 msec) interstimulus intervals in patients relative to their controls, which improved after L‐dopa intake. For comparison with previous reports using transcranial magnetic stimulation we also measured the duration of the EMG silent period when stimuli were given to voluntarily active muscle, and the threshold for evoking an EMG response in both the active and relaxed states. There was no change in the threshold for evoking EMG responses whether muscles were active or relaxed. However, the silent period was significantly prolonged when ON compared with OFF, although in neither state was the duration significantly different from that seen in normals. We suggest that there may be abnormalities of motor cortical inhibitory mechanisms in patients with Parkinson's disease that are not readily detected using threshold or silent period measurements alone.
A clinical and molecular genetic study of dentatorubropallidoluysian atrophy in four european families
Authors: Warner T. T. , Williams L. D. , Walker R. W. H. , Flinter F. , Robb S. A. , Bundey S. E. , Honavar M. , Harding A. E. 
Published: January 2005

AbstractDentatorubropallidoluysian atrophy is a neurodegenerative disorder with characteristic pathology, chiefly described in reports from Japan, and is associated with an unstable CAG trinucleotide repeat in a gene on chromosome 12. We describe four European families, three British and one Maltese, with this mutation. All exhibited autosomal dominant inheritance, and there was evidence for anticipation associated with an increase of the expansion with paternal transmission in two families. Affected chromosomes from patients with dentatorubropallidoluysian atrophy had CAG expansions of 58 to 74 repeats, compared to 7 to 26 in control chromosomes, and the size of repeat was significantly inversely correlated with age of onset. The clinical features were diverse, even within individual families, and comprised a combination of a movement disorder (chorea, myoclonus, dystonia, or parkinsonism), cerebellar ataxia, epilepsy, psychosis, and dementia. A clinical diagnosis of Huntington's disease had been made in affected individuals from all families. Neuropathological examination of 2 patients showed no specific abnormality in one and degenerative changes predominantly affecting the spinal cord in the other. Investigation of 55 patients who might represent sporadic examples of dentatorubropallidoluysian atrophy did not detect any expanded alleles. Dentatorubropallidoluysian atrophy is likely to be more common than previously recognized in non‐Japanese populations, and should be considered in any patient with a dominantly inherited neurodegenerative disorder with the above‐mentioned clinical features.
Increased risk of mortality in alzheimer's disease patients with more advanced educational and occupational attainment
Authors: Stern Yaakov , Tang Ming Xi , Denaro Jean , Mayeux Richard 
Published: January 2005

AbstractA reserve hypothesis suggests that clinical symptoms of Alzheimer's disease (AD) begin earlier in individuals with less education. Therefore, patients with less education might survive longer after diagnosis than those with more education. Two hundred forty‐six subjects with probable AD were following for 1 to 4 years. There were 78 deaths; 30 deaths occurred in the 127 patients whose education was ≤8 years, while 48 deaths occured in the 119 patients with <8 years of education. Cox proportional hazards models adjusted for age, gender, and clinical dementia rating (CDR) showed that patients with more education had increased mortality (continuous variable: RR = 1.06 for each years of education; 95% confidence interval {CI}, 1.01‐1.11; dichotomous variable at 8 yr: RR = 1.76; CI, 1.11‐2.77). This observation might at first seem counterintuitve, since groups with lower socioeconomic status are often at greater mortality risk. It implies that at any level of assessed clinical severity, the underlying pathology of AD is more advanced in patients with more education, resulting in shorter duration of diagnosed disease before death. These findings suggest either that education systematically influences global ratings of disease severity or that education provides a reserve against the clinical manifestation of AD pathology.