bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular genetic characterization of an X‐linked form of Leigh's syndrome
Authors: Matthews P. M. , Marchington D. R. , Squier M. , Land J. , Brown R. M. , Brown G. K. 
Published: January 2005

AbstractWe report a patient with necrotizing encephalomyelopathy (Leigh's syndrome) associated with a deficiency of pyruvate dehydrogenase complex activity. The underlying muration is an A to C transversion in the pyruvate dehydrogenase complex Elα subnit gene. As the Elα subunit is encoded on the X chromosome, this observation confirms that some patients with Leigh's syndrome may potentially exhibit X‐linked inheritance.
The pathophysiology and pharmacology of photic cortical reflex myoclonus
Authors: Artieda Julio , Obeso Jose A. 
Published: January 2005

AbstractWe studied 6 patients with myoclonus elicited by flash stimulation (1–15 Hz). Multichannel electromyographic recording showed a rostrocaudal recruitment order for the generalized myoclonic jerk. In all patients, each flash induced a large (36.9 ± 5.7 μV) frontal biphasic wave with an onset latency of 42 msec that preceded the earliest muscle response in the face by at least 4 msec (range, 4–7 msec), the activity in the biceps by 11 to 14 msec, and the activity in tibialis anterior by 26 to 34 msec. Occipital potentials evoked by the same flash stimulation had a latency of 33.7 msec and were of normal amplitude (2.1 ± 1.2 μV). Brain‐mapping analysis indicated that the frontal activity correlated with the myoclonus originated in the premotor and motor cortices. These findings provide evidence for a cortical origin of this form of stimulus‐sensitive myoclonus in humans. Administration of apomorphine and lisuride (intravenously) and levodopa‐carbidopa (orally) abolished the photic myoclonus. Intravenous 5‐hydroxytryptophan plus carbidopa (orally) and piracetam (orally) were also effective against photic myoclonus. The wide range of drugs active against photic cortical myoclonus suggests the participation of several biochemical mechanisms in its origin.
Differential neural activity in the human temporal lobe evoked by faces of family members and friends
Authors: Seeck M. , Mainwaring N. , Ives J. , Blume H. , Dubuisson D. , Cosgrove R. , Mesulam M.‐M. , Schomer D. L. 
Published: January 2005

AbstractIn 6 patients, depth electrodes revealed differential evoked responses to familiar versus novel faces. These differential responses were obtained in the amygdala, hippocampus, and temporal neocortex but not in the dorsolateral frontal or cingulate cortex. The limbic and temporal structures that differentiated novel from familiar faces did not respond differentially to variations in luminance. Limbic structures and temporal cortex thus appear to participate in face recognition and in encoding the familiarity of visual experiences.
Toward an understanding of the role of glutamate in experimental parkinsonism: Agonist‐sensitive sites in the basal ganglia
Authors: Klockgether Thomas , Turski Lechoslaw 
Published: January 2005

AbstractIncreased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease. However, the mechanisms by which activation of glutamate receptors produce parkinsonism are unknown. Therefore, we examined whether the glutamate agonists N‐methyl‐D‐asparate (NMDA), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA), kainate, and trans‐(±)‐1‐amino‐1,3‐cyclopentanedicarboxylate produce parkinsonism in rats after microapplication into different subregions of the basal ganglia. Electromyographic activity was used as a measure of parkinsonian rigidity. We found that in the rostral striatum, excitation mediated by NMDA but not by non‐NMDA receptors led to parkinsonism. In the substantia nigra pars reticulata, internal pallidal segment/entopeduncular nucleus, and subthalamic nucleus, activation of AMPA/kainate and metabotropic receptors but not of NMDA receptors led to parkinsonian rigidity. Rigidity occurred also in animals bearing ibotenate‐induced lesions of the posterior part of the striatum and of the external pallidal segment, but not in animals with lesions of the anterior striatum, subthalamic nucleus, internal pallidal segment/entopeduncular nucleus, or substantia nigra pars reticulata. These observations suggest that the activation of glutamate receptor subtypes in the basal ganglia may be differentially involved in the expression of parkinsonian symptoms.
Forearm 3‐methylhistidine efflux in myotonic dystrophy
Authors: Rifai Ziad , Kingston William J. , McCraith Brian , Moxley Richard T. 
Published: January 2005

AbstractMyotonic dystrophy is associated with progressive muscular atrophy. To define the mechanism of muscle wasting in this disease, we studied myofibrillar proteolysis in vivo in 8 men moderately affected with myotonic dystrophy, and compared the results with those of 10 normal men. Myofibrillar proteolysis was estimated by measuring the 3‐methylhistidine arteriovenous difference (A – V) and efflux (Q) across the forearm in the postabsorptive state. Plasma 3‐methylhistidine concentrations were determined by high‐performance liquid chromatography with postcolumn o‐phthalaldehyde derivatization and fluorescence detection. Plasma flow to the forearm muscles (F) was estimated to represent 85% of total forearm plasma flow as determined by the indicator‐dilution technique. Forearm 3‐methylhistidine efflux was calculated as: Q = F(A – V). Mean muscle mass (24‐hour creatinine excretion), lean body mass, and forearm volume were decreased in the patients with myotonic dystrophy, confirming the presence of muscle atrophy. Mean forearm 3‐methylhistidine arteriovenous difference and efflux were not significantly different in the two groups. We conclude that myofibrillar protein degradation is not increased in myotonic dystrophy, even when measured in a muscle compartment selectively affected by wasting. Muscle atrophy in myotonic dystrophy is probably the result of defective anabolism rather than accelerated catabolism.
Developmental changes in human γ‐aminobutyric acida receptor subunit composition
Authors: Brooks‐Kayal A. R. , Pritchett D. B. 
Published: January 2005

Abstractγ‐Aminobutyric acid (GABA) is the neurotransmitter at most inhibitory synapses in the human central nervous system. The GABAA receptor, a ligand‐gated ion channel, is the site of action of benzodiazepines, the most widely prescribed neuroactive drugs. It was recently demonstrated that there are multiple subtypes of GABAA receptors. Studies of rodents have shown that receptor subunits are developmentally controlled. The major α subunit of the adult receptor is expressed at low levels before birth. This study, using postmortem human tissue, shows that GABAA receptors are present in significant numbers in the human cerebellum at birth, and the numbers rise threefold by adulthood. Two subtypes of benzodiazepine receptors were detected by binding studies in the neonate, whereas only a single subtype of receptor was detected in the adult cerebellum. Comparison to recombinant human GABAA receptors shows that receptors containing α 1 constitute 50% of the receptors at birth and the percentage rises to over 95% by adulthood. In both cerebral cortex and cerebellum, a dramatic rise in α 1 messenger RNA was observed during development, suggesting that the complement of GABAA receptors differs in infants and adults. These findings have significant implications for normal neurodevelopment as well as for the understanding and treatment of pathophysiological states such as seizures.
Positron emission tomographic studies of dopa‐responsive dystonia and early‐onset idiopathic parkinsonism
Authors: Snow Barry J. , Nygaard Torbjoern G. , Takahashi Hirohide , Calne Donald B. 
Published: January 2005

AbstractThere are two major syndromes presenting in the early decades of life with dystonia and parkinsonism: dopa‐responsive dystonia (DRD) and early‐onset idiopathic parkinsonism (EOIP). DRD presents predominantly in childhood with prominent dystonia and lesser degrees of parkinsonism. EOIP presents before age 40 with parkinsonism (often with associated dystonia). Both disorders are exquisitely sensitive to levodopa, although the long‐term prognosis in each appears to be different. Some have suggested, however, that DRD is a form of EOIP. We performed positron emission tomography with 6‐fluorodopa in 10 patients with DRD and 18 patients with EOIP to study the integrity of their nigrostriatal dopaminergic systems. In DRD, we found normal striatal FD uptake. In contrast, patients with EOIP had reduced striatal FD uptake. We conclude that the pathophysiologies of DRD and EOIP are distinct. Although both disorders presumably represent a deficiency of striatal dopamine, the results suggest that in DRD dopa uptake, decarboxylation, and storage mechanisms are intact. This may explain the sustained response of DRD to low doses of levodopa. 6‐Fluorodopa positron emission tomography distinguishes DRD from EOIP.
Electroclinical signs of benign neonatal familial convulsions
Authors: Hirsch E. , Velez A. , Sellal F. , Maton B. , Grinspan A. , Malafosse A. , Marescaux C. 
Published: January 2005

AbstractBenign neonatal familial convulsions comprise a distinct epileptic syndrome with a autosomal mode of transmission. The electroclinical signs of seizures in this syndrome are not yet well defined. In 3 children from two families presenting with benign neonatal familial convulsions, 14 seizures were recorded during electroencephalographic (EEG)‐video sessions. All seizures occurred during sleep, after a short arousal reaction. Seizures started with bilateral, symmetrical flattening of the EEG for 5 to 19 seconds; simulataneously there was apnea and tonic motor activity. The EEG flattening was followed by a long (1–2‐minute) bilateral discharge of spikes and sharp waves; simultaneously, there were vocalizations, chewing, and focal or generalized clonic activity. The prominence of EEG and motor abnormalities varied between the left and the right from one seizure to the next in any given child. The seizures stopped without EEG or clinical postictal depression. These electroclinical observations suggest that the convulsions of benign neonatal familial convulsions are a form of generalized tonic‐clonic seizure whose expression may be asymmetrical, probably because of the immaturity of the corpus callosum or other structures ensuring seizure synchronization.
Concentric sclerosis (Baló): Morphometric and in situ hybridization study of lesions in six patients
Authors: Yao Da‐Lin , Webster Henry deF. , Hudson Lynn D. , Brenner Michael , Liu Duo‐San , Escobar Alfonso I. , Komoly Samuel 
Published: January 2005

AbstractBrain tissues from 6 patients with concentric sclerosis (Baló) were examined by in situ hybridization, immunocytochemistry, morphometry, and histological methods. The patients were 24 to 48 years old and had progressive cerebral symptoms and signs that lasted 15 to 100 days. Large demyelinative lesions, most frequent in the frontal white matter, contained alternating bands of demyelinated and partly myelinated white matter that were arranged in concentric or mosaic patterns. In the areas of demyelination, axons were relatively well preserved and there were perivascular inflammatory infiltrates. In 2 specimens, lesions contained regions with the characteristic appearance of actively demyelinating multiple sclerosis plaques. Oligodendroglial densities were highest in normal‐appearing white matter, lower in partially myelinated areas, and lowest in demyelinated areas, which also contained many hypertrophic astrocytes closely associated with oligodendroglia. Messenger RNA levels for myelin‐related proteins followed the same pattern; they were lowest in demyelinated areas, higher in partially myelinated areas, and highest in normal‐appearing white matter beyond lesion margins. Our findings suggest that concentric sclerosis is a variant of multiple sclerosis, that oligodendroglial loss is important in the pathogenesis of demyelination, and that partially myelinated areas probably represent stages of ongoing myelin breakdown rather than remyelination of previously demyelinated areas.
Localization of non–N‐methyl‐D‐aspartate glutamate receptors in normal and Alzheimer hippocampal formation
Authors: Hyman Bradley T. , Penney John B. , Blackstone Craig D. , Young Anne B. 
Published: January 2005

AbstractThe hippocampi and adjacent temporal cortices of 24 human brains were examined with antibodies to the GluR1, GluR2/3, and GluR4 subunits of the D,L‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid–preferring glutamate receptor. GluR1 immunoreactivity was most dense in the dentate gyrus, with lower densities in other hippocampal and cortical regions. GluR2/3 immunoreactivity was the most intense of the three antibodies, with high levels throughout most hippocampal subfields, where it was localized to cell bodies, proximal axons, and dendrites. GluR4 immunoreactivity was very sparse in all regions. In Alzheimer's disease brains, the general pattern of staining was similar to that seen in control brains. GluR1 and GluR4 immunoreactivity was seen in some but not all neuritic plaques. All three antibodies recognized some neurons undergoing neurofibrillary degeneration.
Aspartame has no effect on seizures or epileptiform discharges in epileptic children
Authors: Shaywitz B. A. , Anderson G. M. , Novotny E. J. , Ebersole J. S. , Sullivan C. M. , Gillespie S. M. 
Published: January 2005

AbstractThe effects of aspartame (L‐aspartyl‐L‐phenylalanine methyl ester; APM) on the neurological status of children with well‐documented seizures were examined in a randomized, double‐blind, placebo‐controlled, crossover study. We report on 10 children (5 boys, 5 girls, ages 5–13 yr) who were tested for 2 weeks each on APM and placebo (single morning dose, 34 mg/kg). Seven children had generalized convulsions with 4 also having absence episodes. One child had absence seizures and 2 had complex partial seizures only. On each arm of the study, children were admitted to the hospital for a standard 21‐lead electroencephalogram (EEG), continuous 24‐hour cassette EEG, and determination of biochemical variables in plasma and urine. Subjects completed the Subjects Treatment Emergent Symptoms Scale (STESS) and parents the Conners Behavior Rating Scale. There were no significant differences between APM and placebo in the standard EEG or 24‐hour EEG. No differences were noted for the STESS or the Conners ratings, and no differences were noted for any of the biochemical measures (except for expected increases in phenylalanine and tyrosine after APM). Our findings indicate that, in this group of vulnerable children, APM does not provoke seizures.
Evidence for long‐term survival and function of dopaminergic grafts in progressive Parkinson's disease
Authors: Lindvall Olle , Sawle Guy , Widner Håkan , Rothwell John C. , Björklund Anders , Brooks David , Brundin Patrik , Frackowiak Richard , Marsden C. David , Odin Per , Rehncrona Stig 
Published: January 2005

AbstractTwo patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine‐rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6‐L‐[18F]‐fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the “off” phase, and by a prolongation of the effect of a single dose of L‐dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L‐dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non‐grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.
Lateralization of temporal lobe epilepsy based on regional metabolic abnormalities in proton magnetic resonance spectroscopic images
Authors: Cendes Fernando , Andermann Frederick , Preul Mark C. , Arnold Douglas L. 
Published: January 2005

AbstractMagnetic resonance spectroscopic imaging (MRSI) is capable of determining the spatial distribution in vivo of cerebral metabolites, including N‐acetylaspartate (NAA), a compound found only in neurons. We used this technique in 10 patients with temporal lobe epilepsy (TLE) to determine the location of maximal neuronal/axonal loss or damage and to evaluate the potential of MRSI for presurgical lateralization. Asymmetry of the relative resonance intensity of NAA to creatine was determined for mid and posterior regions of the temporal lobes defined anatomically and also for “metabolic lesions” defined as the regions of maximal abnormality on MRSI. MRSI revealed decreased relative signal intensity in at least one temporal lobe of all patients. Two patients had a widespread reduction in NAA in both temporal lobes. The region of maximal abnormality was usually in the posterior temporal lobe but sometimes in the mid temporal lobe. The side of lowest NAA was ipsilateral to the clinical electroencephalographic lateralization in all patients. Lateralization based on NAA to creatine correlated with the atrophy of amygdala and hippocampus in 8 patients who showed this on magnetic resonance imaging volumetric measurements. MRSI can demonstrate regional neuronal loss or damage that correlates with clinical electroencephalographic and structural lateralization in temporal lobe epilepsy. The ability to identify a region of maximal metabolic abnormality on spectroscopic images may confer greater sensitivity than that available from single voxel methods. The maximal metabolic abnormality may not be located in a voxel defined a priori, and based on anatomical considerations, without knowledge of the distribution of the metabolic abnormality.
Human prion diseases
Authors: Prusiner Stanley B. , Hsiao Karen K. 
Published: January 2005

AbstractThe prion diseases, sometimes referred to as the “transmissible spongiform encephalopathies,” include kuru, Creutzfeldt‐Jakob disease, and Gerstmann‐Sträussler‐Scheinker disease of humans as well as scrapie and bovine spongiform encephalopathy of animals. For many years, the prion diseases were thought to be caused by viruses despite intriguing evidence to the contrary. The unique characteristic common to all of these disorders, whether sporadic, dominantly inherited, or acquired by infection, is that they involve the aberrant metabolism of the prion protein (PrP). In many cases, the cellular prion protein is converted into the scrapie isoform by a posttranslational process that involves a conformational change. Often, the human prion diseases are transmissible to experimental animals and all of the inherited prion diseases segregate with PrP gene mutations.
Single muscle fiber analysis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS)
Authors: Tokunaga Makoto , Mita Shuji , Murakami Tatsufumi , Kumamoto Toshihide , Uchino Makoto , Nonaka Ikuya , Ando Masayuki 
Published: January 2005

AbstractWe examined muscle sections from 3 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS), using single‐fiber polymerase chain reaction, histochemistry, and in situ hybridization. Most type 1 ragged‐red fibers showed positive cytochrome c oxidase activity at the subsarcolemmal region, while type 2 ragged‐red fibers had little cytochrome c oxidase activity. However, there was no difference in the amount of total (mutant and wild‐type) mitochondrial DNAs (mtDNAs) and the proportion of mutant mtDNA between type 1 and type 2 ragged‐red fibers. These observations suggest that mitochondrial proliferation and nuclear factors affect muscle pathology, including cytochrome c oxidase activity, in MELAS. Total mtDNAs were greatly increased in ragged‐red fibers (about 5–17 times over those in non–ragged‐red fibers). The proportion of mutant mtDNA was significantly higher in ragged‐red fibers (88.1 ± 5.5%) than in non–ragged‐red fibers (63.2 ± 21.6%). Thus, the amount of wild‐type mtDNA as well as mutant mtDNA was increased in ragged‐red fibers in MELAS, failing to support the contention of a replicative advantage of mutant mtDNA. The proportion of mutant mtDNA was significantly higher in the strongly succinate dehydrogenase–reactive blood vessels (83.2 + 4.2%) than in non–succinate dehydrogenase–reactive blood vessels (38.8 ± 16.2%). It seems likely that systemic vascular abnormalities involving cerebral vessels lead to the evolution of stroke‐like episodes in MELAS.
Axonal injury and membrane alterations in Alzheimer's disease suggested by in vivo proton magnetic resonance spectroscopic imaging
Authors: Meyrhoff D. J. , MacKay S. , Constans J.‐M. , Norman D. , Van Dyke C. , Fein G. , Weiner M. W. 
Published: January 2005

AbstractWe used spin‐echo magnetic resonance imaging and prton magnetic resonance spectroscopic imaging in 8 patients with probable Alzheimer's disease and in 10 age‐matched elderly control subjects to assess the effects of Alzheimer's disease on the brain. On magnetic resonance images the patients showed signficant ventricular enlargements relative to the control subjects. We measured the distribution and relative signal intensities of N‐acetylaspartate (a putative neuronal marker), of choline residues representing lipid metabolities, and of creatine‐containing metabolites in a large section of the centrum semiovale containing white and mesial gray matter. Throughout the white matter of the patients with Alzheimer's disease compared to elderly control subjects, N‐acetylaspartate was decreased relative to choline (N‐acetylaspartate–choline ration) and creatine‐containing metabolities (N‐acetylaspartate–creatine ratio) with no changes in the choline‐creatine ratio. The N‐acetylaspartate–choline ratio was lower and choline‐creatine higher in the mesial gray matter of AD patients relative to elderly controls. The posterior section of the centrum semiovale in the patients showed increased choline‐creatine and choline–N‐acetylaspartate ratios with the N‐acetylaspartate–creatine ratio unchanged between the patients and control subjects. These spectroscopic findings give suggestive evidence of diffuse axonal injury and membrane alterations in gray and white matter of the centrum semiovale in patients with Alzheimer's disease.