bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lowered cerebral glucose utilization in amyotrophic lateral sclerosis
Authors: Dalakas Marinos C. , Hatazawa Jun , Brooks Rodney A , Di Chiro Giovanni 
Published: January 2005

AbstractRegional cerebral metabolic rates for glucose (rCMRGlc) were analyzed in 19 studies of 12 patients with amyotrophic lateral sclerosis (ALS) by positron emission tomography (PET) with {18F}2‐fluoro‐2‐deoxy‐D‐glucose. In the 8 ALS patients with upper motor neuron signs, the mean cortical rCMRGlc was significantly lower than in 11 age‐matched control subjects (p < 0.001). The degree of hypometabolism correlated with the duration of the clinical signs and extended throughout the cortex and basal ganglia, but not to the cerebellum. Of the 4 such patients who had repeat PET scans, 3 demonstrated significant subsequent reduction in the rCMRGlc, corresponding to the worsening of the clinical picture. In contrast, 4 ALS patients with disease confined to lower motor neurons and 3 patients with lower motor neuron disease from old paralytic poliomyelitis had normal or near‐normal rCMRGlc throughout the brain. Because histological evidence shows no generalized neuronal cell loss in the cortex of ALS patients, including in some cases the primary motor regions, the demonstration of severe generalized hypometabolism in structurally normal cortex indicates that some cortical neurons exist in a state of neuronal nonfunction, rather than cell death, and that anatomoclinical correlations may be more complex. The data also indicate that ALS with upper motor neuron involvement extends beyond the corticospinal tracts and differs in cortical function from the ALS confined to lower motor neurons or the other lower motor neuron disorders.
Huntington's disease: Changes in tachykinin content in postmortem brains
Authors: Arai Heii , Emson Piers C , Carrasco Luis H. 
Published: January 2005

AbstractSubstance P, neurokinin A, neuropeptide K, and neurokinin B were measured in both control (neurologically normal) and Huntington's disease brains obtained post mortem. All four peptides were significantly reduced in the substantia nigra of Huntington's disease patients compared with the control group. No differences were observed in frontal or temporal cortex except that neuropeptide K was significantly reduced in the frontal cortex of Huntington's disease cases. Correlation of the cell loss observed in the striatum and the tachykinin depletions detected in the substantia nigra in the Huntington's disease brains showed that the degree of cell loss agreed well with the extent of tachykinin depletion. Results of double‐staining immunocytochemistry were consistent with the coexistence of substance P and neurokinin A in the substantia nigra of control brains and showed a marked depletion of immunoreactivity to both in Huntington's disease brains.
Immunoglobulins of Lambert‐Eaton myasthenic syndrome inhibit rat pituitary hormone release
Authors: Login Ivan S. , Kim Yong I. , Judd Allan M. , Spangelo Bryan L. , MacLeod Robert M. 
Published: January 2005

AbstractWe speculated that IgG from patients with Lambert‐Eaton myasthenic syndrome (LES) would inhibit calciumdependent hormone secretion in rat anterior pituitary (AP) cells. Primary cultures of normal AP cells were continuously exposed to crude IgG from an LES patient or from healthy control subjects, and the incubation media were assayed for prolactin (PRL) or growth hormone (GH). The LES IgG caused a time‐ and concentration‐dependent reduction of PRL and GH release compared with control IgG over 0.5 to 48 hours using concentrations of 0.01 to 4.0 mg/ml. The calcium‐channel activator maitotoxin stimulated 45Ca2+ uptake and PRL release from AP cells under control conditions, and the LES IgG significantly reduced both actions of maitotoxin. Thus LES IgG appears to modulate an AP antigenic site, perhaps representing an integral component of voltage‐gated calcium channels that may share properties with similar presynaptic elements at the neuromuscular junction.
In vivo 31P and in vitro 1H nuclear magnetic resonance study of hypoglycemia during neonatal seizure
Authors: Young Richard S. K. , Cowan Barrett E. , Petroff Ognen A. C. , Novotny Edward , Dunham Susan L. , Briggs Richard W. 
Published: January 2005

AbstractTo examine the hypothesis that hypoglycemia has an adverse effect on brain energy state during seizure, neonatal dogs were subjected to bicuculline‐induced seizure while hyperglycemic, normoglycemic, or hypoglycemic. Cerebral blood flow increased and remained elevated in all animals subjected to seizure, regardless of blood or brain glucose concentration. In vivo 31P nuclear magnetic resonance spectroscopy disclosed a small (10–20%) decrease in adenosine triphosphate levels and a greater (20–40%) decline in phosphocreatine levels in animals experiencing seizure, irrespective of whether they were hyper‐, normo‐, or hypoglycemic. In vitro analysis of brain extracts with 1H nuclear magnetic resonance spectroscopy disclosed a significant elevation of lactate in all seizing animals. There were differences in brain alanine, glycine, and β‐hydroxybutyrate levels between the hyperglycemia‐seizure and hypoglycemia‐seizure groups. Alternate substrates such as lactate, fatty acids, or amino acids may be used when neonatal seizure is complicated by hypoglycemia, thereby preventing further deterioration of brain metabolic state.
Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease
Authors: Kowall Neil W. , Kosik Kenneth S. 
Published: January 2005

AbstractThe microtubule‐associated protein tau, a major antigenic component of paired helical filaments, has been demonstrated in neurofibrillary tangles and in neurites of senile plaques. With optimal fixation and histochemical methods, we show the normal axonal location of tau protein in human cerebral cortex and the striking alterations of tau distribution that affect the cortical neuropil in Alzheimer's disease. Normally, cortical tau‐immunoreactive fiber bundles form a pattern resembling that seen with myelin stains. The prominence of white matter staining suggests that tau may be especially enriched in projection systems. Alzheimer's disease causes massive axonal disruption and the dislocation of tau protein from its usual axonal domain into neuronal cell bodies, dendrites, and presynaptic regions. The normal pattern of axonal staining in cortex is disrupted and white matter staining is reduced. Prominent abnormal tau‐immunoreactive neuropil fibers are densely present even in cortical regions without classical neurofibrillary tangle and senile plaque formation. The striking neuropil abnormalities, revealed by the aberrant localization of tau protein, are likely to contribute to neuronal dysfunction in Alzheimer's disease.
Somatic and autonomic function in progressive autonomic failure and multiple system atrophy
Authors: Cohen Jeffrey , Low Phillip , Fealey Robert , Sheps Sheldon , Jiang Nai‐Siang 
Published: January 2005

AbstractWe studied 62 consecutive patients with progressive autonomic failure (PAF) or multiple system atrophy (MSA) (26 PAF; 36 MSA). Patients were well matched in age (67 vs 66 years), duration (39 vs 36 months), and severity of autonomic failure (median values for PAF and MSA). Peripheral somatic neuropathy occurred in 2 patients with PAF and 7 patients with MSA. Postganglionic sudomotor and vasomotor functions were studied using the quantitative sudomotor axon reflex test and supine plasma norepinephrine. The extent and severity of autonomic failure were assessed by the thermoregulatory sweat test, by heart rate responses to deep breathing and the Valsalva maneuver, and by blood pressure recordings. Severe and widespread anhidrosis was found in both PAF and MSA patients. Postganglionic sudomotor failure occurred at the forearm in 50% each of PAF and MSA patients and at the foot in 69% and 66% of PAF and MSA patients, respectively. However, postganglionic sudomotor function was preserved in some patients with anhidrosis on thermoregulatory sweat test, indicating a preganglionic lesion. Vagal abnormalities were found in 77% and 81% of PAF and MSA patients. Supine plasma free norepinephrine values were significantly reduced in PAF (p < 0.001), but not in MSA, patients. Standing plasma norepinephrine values were reduced in both PAF (p < 0.001) and MSA (p < 0.001) patients. We conclude the following: (1) PAF is characterized by combined postganglionic sudomotor and adrenergic failure. (2) MSA is associated with a similar frequency of postganglionic sudomotor failure, but postganglionic adrenergic denervation was uncommon. (3) Preganglionic neuron is also involved in both disorders, but more severely in MSA. (4) Somatic neuropathy may occur.
Magnetic resonance imaging in isolated noncompressive spinal cord syndromes
Authors: Miller D. H. , McDonald W. I. , Blumhardt L. D. , du Boulay G. H. , Halliday A. M. , Johnson G. , Kendall B. E. , Kingsley D. P. E. , MacManus D. G. , Moseley I. F. , Rudge P. , Sandercock P. A. G. 
Published: January 2005

AbstractThe frequency with which patients presenting with acute or chronic noncompressive cord syndromes subsequently develop multiple sclerosis is uncertain. Magnetic resonance imaging (MRI) was performed on 121 patients with such syndromes to determine the frequency of asymptomatic brain lesions and to assess the sensitivity of MRI in detecting the local cord lesion. MRI findings were compared with those from visual, brainstem, and somatosensory evoked potentials (VEPs, BAEPs, SEPs), and cerebrospinal fluid electrophoresis. Lesions were seen in the appropriate cord region in 47 of 73 patients (64%) with a cervical syndrome, and in 7 of 25 patients (28%) with a thoracic or lumbar syndrome. MRI demonstrated more cervical lesions than did SEPs, but fewer thoracic or lumbar lesions. Cord swelling was seen in 6 patients and atrophy in 10. Of those with acute syndromes, abnormalities were seen with brain MRI in 18 of 32 patients (56%), with VEPs in 2 of 30 patients (7%), and with BAEPs in 2 of 24 patients (8%). In patients with chronic syndromes, abnormalities were seen with brain MRI in 73 of 89 patients (82%), with VEPs in 22 of 80 patients (28%), and with BAEPs in 12 of 62 patients (19%). Brain MRI was thus more sensitive than evoked potentials were in establishing multiplicity of lesions. However, in acute syndromes, it was not possible to diagnose multiple sclerosis from a single abnormal brain scan. In chronic syndromes, a diagnosis of clinically probable multiple sclerosis could be made from one scan, provided there was no better explanation for the abnormalities: the added presence of oligoclonal bands allows a diagnosis of laboratory‐supported, definite multiple sclerosis as was the case in 28 patients in this series.
Kynurenate inhibition of cell excitation decreases stroke size and deficits
Authors: Germano Isabelle M. , Pitts Lawrence H. , Meldrum Brian S. , Bartkowski Henry M. , Simon Roger P. 
Published: January 2005

AbstractPharmacological inhibition of excitatory neurotransmission attenuates cell death in models of global ischemia/reperfusion and hypoglycemia. The current investigations extend these observations to a model of focal ischemia. Kynurenic acid, a broad‐spectrum antagonist at excitatory amino acid receptors, was used as treatment (300 mg/kg; 3 doses at 4‐hour intervals) before and after focal cerebral ischemia in rats (n = 54). Preischemia but not 1 hour postischemia treatment with kynurenate attenuated infarction size (p < 0.001) and improved neurological outcome (p < 0.001) studied at 24 hours after injury. These data support the role of excitatory neurotransmission in acute neuronal injury and support pharmacological inhibition of cell excitation as a potential therapy for stroke.
Axonal transport in neurological disease
Authors: Griffin John W. , Watson Danny F. 
Published: January 2005

AbstractThe axonal transport systems have a wide variety of primary roles and secondary responses in neurological disease processes. Recent advances in understanding these roles have built on the increasingly detailed insights into the cell biology of the axon and its supporting cells. Fast transport is a microtubule‐based system of bidirectional movement of membranous organelles; the mechanism of translocation of these organelles involves novel proteins, including the recently described protein of fast anterograde transport, kinesin. Slow transport conveys the major cytoskeletal elements, microtubules, and neurofilaments. Several types of structural changes in diseased nerve fibers are understood in terms of underlying transport abnormalities. Altered slow transport of neurofilaments produces changes in axonal caliber (swelling or atrophy) and is involved in some types of perikaryal neurofibrillary abnormality. Secondary changes in slow axonal transport—for example, the reordered synthesis and delivery of cytoskeletal proteins after axotomy—also can produce changes in axonal caliber. Secondary demyelination can be a prominent late consequence of a sustained alteration of neurofilament transport. Impaired fast transport is found in experimental models of distal axonal degeneration (dying back). Retrograde axonal transport provides access to the central nervous system for agents such as polio virus and tetanus toxin, as well as access for known and hypothetical trophic factors. Correlative studies of axonal transport, axonal morphometry, cytoskeletal ultrastructure, and molecular biology of cytoskeletal proteins are providing extremely detailed reconstructions of the pathogenesis of experimental models of neurological disorders. A major challenge lies in the extension of these approaches to clinical studies.
The inheritance of alzheimer's disease: A new interpretation
Authors: Fitch Naomi , Becker Rubin , Heller Anita 
Published: January 2005

AbstractNinety‐one families of Alzheimer patients were studied to determine the proportion of familial cases, to obtain pedigrees for the analysis of the mode of inheritance, and to look for clinical differences between the familial and the nonfamilial cases. The diagnosis was confirmed by autopsy in 26 cases. Thirty‐nine cases (43%) were familial, which is defined as more than one case in the family. Our interpretation of the pedigree data is that Alzheimer's disease is etiologically heterogeneous: it may be genetic or sporadic. In the familial type we think that the disease is inherited as an autosomal dominant, with a wide range of age of onset within a family. In one‐third of these families the gene is not expressed until over age 70. No clinical differences were found between the familial and the sporadic groups.
Quantitative relations between hypertonia and stretch reflex threshold in spastic hemiparesis
Authors: Powers R. K. , Marder‐Meyer J. , Rymer W. Z. 
Published: January 2005

AbstractThe relative contributions of variations in stretch reflex threshold and total joint stiffness to changes in stretch‐evoked torque were assessed in the spastic elbow muscles of 14 hemiparetic spastic subjects. For a given subject, variations in torque, measured after a constant angular deflection, were mediated largely by changes in stretch reflex threshold, rather than by changes in reflex stiffness. Between‐subject comparisons were sensitive to stiffness differences between limbs, but reflex thresholds were still broadly correlated with torque magnitude, suggesting that reductions in stretch reflex threshold are uniformly present in spastic muscles. These findings, coupled with the apparent similarity of reflex stiffness estimates in voluntarily activated spastic and normal muscles, suggest that the central disturbance in spasticity is a reduction in the threshold of the stretch reflex, without a significant enhancement of reflex gain.
Focal spike‐induced cerebral dysfunction is related to the after‐coming slow wave
Authors: Shewmon D. Alan , Erwin Roland J. 
Published: January 2005

AbstractBy means of a computerized system of spike detection, presentation of visual stimuli, and registration of reaction times (RTs), we have shown previously that focal posterior interictal spikes cause transiently prolonged RT and increased nonperception and misperception of stimuli, especially contralateral to the spike. We report here the temporal profile of this phenomenon, ascertained by systematically increasing a delay between spike and stimulus‐flash, until the latter was well beyond the limits of the entire spike‐wave complex. In each of two subjects, the spike effect began just before the spike and ended with the termination of the after‐coming slow wave. For stimuli with identical delays following spikes, RTs were significantly prolonged if the end of the slow wave overlapped the stimulus, and not otherwise. In one subject, who had an amplitude dissociation between spikes and after‐coming slow waves, the prolongation of RT was associated with the larger waves, regardless of spike amplitude. These findings suggest that the after‐coming slow wave (surround hyperpolarization) transiently disrupts aspects of cortical functioning, in addition to whatever effect the spike itself may have. Focal spike‐wave‐induced cortical dysfunction may be relevant to a variety of interictal cognitive disorders.
Monoclonal antibody analysis of mononuclear cells in myopathies. IV: Cell‐mediated cytotoxicity and muscle fiber necrosis
Authors: Arahata Kiichi , Engel Andrew G. 
Published: January 2005

AbstractCell‐mediated muscle fiber injury occurs in inclusion body myositis (IBM), polymyositis (PM), and even in Duchenne dystrophy (DD). Most of the autoaggressive cells are T cells and macrophages, but some are killer/natural killer (K/NK) cells. We here compare the frequencies per 1,000 muscle fibers of endomysial K/NK cells of varying cytotoxicity with those of T cells and macrophages in 8 cases each of IBM, PM, and DD. Two‐micrometer serial cryostat sections were analyzed. The Leu‐4 marker, present on all T cells and some K/NK cells, and the Leu‐7 and Leu‐11 markers, present on K/NK cells, were localized by paired immunofluorescence. Macrophages were demonstrated by the acid phosphatase reaction. In IBM, PM and DD, the respective average cell counts per 1,000 muscle fibers were: Leu‐4+7− cells (T cells not expressing a K/NK marker)—710, 530, and 59; Leu‐4+7+ cells (K/NK cells of low K/NK cytotoxicity)—294, 163, and 13; Leu‐4−7+ cells (K/NK cells of intermediate cytotoxicity)—32, 10, and 2; and macrophages—292, 251, and 38. Leu 11+ K/NK cells that have the highest killing activity were virtually absent in all cases. The data suggest a limited role for antigen and major histocompatibility complex unrestricted K/NK cells, as compared with antigen‐specific and major histocompatibility complex‐restricted T cells, in IBM and PM. Further, the findings cast doubt on the significance of either T cells or K/NK cells in mature muscle in DD. We also determined the frequencies of nonnecrotic muscle fibers invaded by mononuclear cells (i.e., fibers affected by cell‐mediated cytotoxicity) and of necrotic fibers, for these frequencies are indicators of two major mechanisms of muscle fiber injury in myopathies. Nonnecrotic invaded fibers were 5.5 times more frequent than necrotic fibers in IBM; the converse was true in DD; and the two mechanisms were equally frequent in PM.
Intraneuronal and extracellular neurofibrillary tangles exhibit mutually exclusive cytoskeletal antigens
Authors: Schmidt M. L. , Gur R. E. , Gur R. C. , Trojanowski J. Q. 
Published: January 2005

AbstractWe examined the possibility that neurofibrillary tangles (NFTs) were heterogeneous in postmortem hippocampus from 22 patients with or without senile dementia of the Alzheimer type. Intraneuronal NFTs and extracellular, or “ghost”, NFTs were recognized in situ by only one or the other of two monoclonal antibodies. The first monoclonal antibody, RMO87, stained only intraneuronal NFTs and is specific for phosphate‐dependent epitopes in tau and the two high molecular weight neurofilament proteins. The second monoclonal antibody, 2.2B10, is specific for glial fibrillary acidic protein, and it stained only the RMO87‐negative extracellular NFTs. Treatment of sections with alkaline phosphatase or sodium dodecyl sulfate, and the isolation of NFTs from hippocampus, did not expose RMO87 binding sites in extracellular NFTs. These observations indicate that neurofilament‐like and tau‐like epitopes can be lost from NFTs in situ, and that at least two populations of morphologically and immunochemically distinct NFTs exist.
Two distinct deficits of visual tracking caused by unilateral lesions of cerebral cortex in humans
Authors: Thurston Stephen E. , Leigh R. John , Crawford Trevor , Thompson Alan , Kennard Christopher 
Published: January 2005

AbstractWe studied horizontal visual tracking in 20 patients with unilateral cerebral lesions and in 10 age‐matched control subjects. Five patients, all with posterior lesions, showed impaired smooth pursuit of predictable targets moving toward the side of the cerebral lesion. Using nonpredictable step‐ramp stimuli, we identified two distinct deficits of visual tracking. The first was a unidirectional deficit of smooth pursuit, for targets moving toward the side of the lesion, in response to stimuli presented into either visual hemifield. The second deficit, identified in a sixth patient who did not show pursuit asymmetry to predictable targets, was a bidirectional inability to estimate the speed of a moving target in the visual hemifield contralateral to the side of the lesion; this caused inaccurate saccades to moving (but not stationary) targets and impaired smooth pursuit initiation. These visual tracking deficits were independent of homonymous hemianopia or hemispatial neglect. These two tracking deficits are similar to those described in rhesus monkeys with lesions of the medial superior temporal and middle temporal visual areas.
Clinical and electrophysiological studies of human immunodeficiency virus—seropositive men without AIDS
Authors: Smith T. , Jakobsen J. , Gaub J. , Helweg‐Larsen S. , Trojaborg W. 
Published: January 2005

AbstractMotor weakness and ataxia of lower limbs and abnormalities of somatosensory evoked potentials occur in many patients with the acquired immunodeficiency syndrome (AIDS). We studied 15 human immunodeficiency virus‐seropositive subjects without AIDS and found no clinical neurological abnormalities. The mean latency of the brainstem auditory evoked potential (peak V) was increased, suggesting a central defect. Despite normal peripheral nerve conduction along the tibial nerve, the mean latency of the spinal cord potential of the twelfth thoracic vertebra was increased compared with normal, possibly indicating an incipient conduction defect at or near the spinal root ganglion or lumbar spinal cord.
Stimulation of lipolytic enzymes in alzheimer's disease
Authors: Farooqui Akhlaq A. , Liss Leopold , Horrocks Lloyd A. 
Published: January 2005

AbstractThe activities of monoacylglycerol and diacylglycerol lipases were 6 to 8 times higher in plasma membrane and synaptosomal plasma membrane fractions of nucleus basalis from patients with Alzheimer's disease than in those membranes from normal human brains. Membranes from the hippocampus region of Alzheimer‐affected brains also showed consistently higher activities of monoacylglycerol and diacylglycerol lipases than those from control brains. These results indicate a stimulation of lipolytic enzymes in nucleus basalis and hippocampus regions in patients with Alzheimer's disease.