bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positron emission tomographic measurement of cerebral blood flow and temporal lobectomy
Authors: Theodore William H. , Gaillard William D. , Sato Susumu , Kufta Conrad , Leiderman Deborah 
Published: January 2005

AbstractWe used positron emission tomography (PET) and bolus injection of H215O to measure interictal cerebral blood flow (CBF) in 32 patients who had temporal lobectomy for uncontrolled complex partial seizures. Seizure focus localization was confirmed by ictal video–electroencephalographic (video‐EEG) telemetry, and patients who had imaging findings suggesting the presence of a tumor were excluded. PET‐CBF studies were interpreted using a standard template by raters blinded to EEG and clinical data, and were not used in surgical planning. After surgery, patients were followed for 32 ± 18 months. Twenty‐six patients were seizure free and 6 had persistent seizures. Mean lateral temporal hypoperfusion was 8 ± 14% in patients who became seizure free and 9 ± 6% in patients with persistent seizures. Fourteen patients had at least 15%, and 11 at least 20% hypoperfusion, but were not more likely to be seizure free. Three additional patients had 15 to 20% hypoperfusion in the temporal lobe contralateral to their EEG focus. PET measurement of CBF using bolus H215O should not be used to help select patients for temporal lobectomy.
Viability thresholds and the penumbra of focal ischemia
Authors: Hossmann K‐A. 
Published: January 2005

AbstractThe classic concept of the viability thresholds of ischemia differentiates between two critical flow rates, the threshold of electrical failure and the threshold of membrane failure. These thresholds mark the upper and lower flow limits of the ischemic penumbra which is thought ot suffer only functional but not structural injury. Recent studies of the functional and metabolic disturbances suggest a more complex pattern of thresholds. At declining flow rates, protein synthesis is inhibited at first (at a threshold of about 0.55 ml/gm/min), followed by a stimulation of anaerobic glycolysis (at 0.35 ml/gm/min), the release of neurotransmitters and the beginning disturbance of energy metabolism (at about 0.20 ml/min), and finally the anoxic depolariztion (<0.15 ml/gm/min). The penumbra, as defined by the classic flow thresholds, does not remain viable for extended periods. Since viability of the tissue requires maintenance of energy‐dependent metabolic processes, penumbra is redefined as a region of constrained blood supply in which the energy metabolism is preserved. Imaging of the penumbra by combining autoradiographic cerebral blood flow measurements with bioluminescent images of adenosine triphosphate (ATP) demonstrates a gradual expansion of the infarct core (in which ATP is depleted) into the penumbra until, after a few hours, the penumbra has disappeared. It is suggested that the limited survival of the penumbra is due to periinfarct depolarizations, which result in repeated episodes of tissue hypoxia, because the increased metabolic workload is not coupled to an adequate increase of collateral blood supply. This explains pharmacological suppression of periinfarct depolarizations lowering the threshold of metabolic disturbances and reducing the volume of the ischemic infarct.
Polymyositis inpatients infected with human T‐cell leukemia virus type I: The role of the virus in the cause of the disease
Authors: Leon‐Monzon Marta , Illa Isabel , Dalakas Marinos C. 
Published: January 2005

AbstractTo investigate the mechanism of polymyositis in human T‐cell leukemia virus type 1 (HTLV‐I) infection, we studied 6 HTLV‐I–positive patients, 3 with polymyositis and 3 with adult T‐cell leukemia but without clinical signs of muscle disease, by (a) quantitative single or double immunocytochemistry on serial 4‐μm‐thick muscle biopsy sections using antibodies to lymphocyte subsets, major histocompatibility complex (MHC) antigens, and HTLV‐I proteins; (b) polymerase chain reaction using HTLV‐I primers in the RNA and DNA extrcted from 50 μg of muscle tissue or from serial 5‐μm‐thick fresh‐frozen tissue sections; and (c) cocultures of the patients' HTLV‐I–positive peripher blood lymphocytes with their homologous muscles searching for replication of HTLV‐I within the myotubes. In the muscle of patients with HTLV‐I–associated myopathy, the predominant endomysial cells surrounding healthy muscle fibers were CD8+ cells followed by CD4+ cells and macrophages. MHC‐I antigens were ubiquitous in the muscles of all 6 patients, even in those without endomysial inflammation. HTLV‐I sequences were amplified from the whole muscle biopsy specimens but the cells harboring viral antigens were rare endomysial macrophages and not muscle fibers. Although HTLV‐I sequences were amplified from all the patients' peripheral blood lymphocytes, these cells did not exert myotoxicity or resulted in viral replication in cocultures with their homologous myotubes. We conclude that in HTLV‐I polymyositis (a) the HTLV‐I sequences amplified from the whole muscle biopsy specimens are related to scattered HTLV‐I–positive endomysial macrophages; (b) HTLV‐I and HTLV‐I–positive lymphocytes do not infect the muscle in vivo or in vitro; and (c) the virus, which perists in tissues other than muscle, triggers the activationof autoaggressive T cells that cause a T‐cell–mediated and MHC‐I–restricted myocytotoxicity.
Age‐dependent decline of nigrostriatal dopaminergic function: A positron emission tomographic study of grandparents and their grandchildren
Authors: Cordes Michael , Snow Barry J. , Cooper Sandra , Schulzer Michael , Pate Brian D. , Ruth Thomas J. , Calne Donald B. 
Published: January 2005

AbstractDespite postmortem evidence for an age‐related decline in nigrostriatal dopaminergic function, positron emission tomography (PET) studies have produced inconsistent results. This may be due to differences inmethods or of subject selection. To investigate further the effect of age on dopaminergic function, we performed PET with 6‐L‐[18F]fluorodopa (FD) on 12 pairs of grandchildren and their grandparents. The FD uptake rate constant (Ki) was calculated using a graphical method for the whole striatum to avoid confounding of the results by striatal atrophy. The mean Ki was significantly lower in grandparents (p = 0.020). These PET observations represent in vivo confirmation of postmortem evidence that nigrostriatal dopaminergic function declines with aging.
Oral administration of acetylcholine receptor: Effects on experimental myasthenia gravis
Authors: Okumura Seiichi , McIntosh Kevin , Drachman Daniel B. 
Published: January 2005

AbstractThe abnormality in myasthenia gravis (MG) is a deficiency of acetylcholine receptors (AChRs) at neuromuscular junctions due to an antibody‐mediated autoimmune attack. Although immunosuppressive drugs are usually beneficial in MG, they produce generalized suppression of the immune system. Treatment should specifically inhibit the immune response to AChR. Oral administration of an antigen may induce specific tolerance and has recently been tested for treatment of several cell‐mediated experimental and human autoimmune diseases. In this study, we investigated the effects of oral administration of AChR in an experimental rat model of MG (EAMG), which is antibody mediated. Lewis rats were fed various doses of purified or unpurified Torpedo AChR, or a control antigen, ovalbumin (OVA). They were then immunized with AChR or OVA. We measured antibody responses to Torpedo AChR or OVR, autoantibody responses to rat AChR, cellular responses, cellular suppressive effects, and clinical status. Our results showed that AChR feeding prevented clinical signs of EAMG. It initially primed, then inhibited, antibody responses to foreign (Torpedo) AChR and self (rat) AChR, with a delayed onset. Cellular responses to AChR, measured by lymphocyte proliferation and interleukin‐2 production, were markedly inhibited. The effects were dose dependent. Unpurified AChR given in comparable amounts was far less effective than pure AChR. OVA feeding had similar, but even more potent effects on humoral and cellular immune responses to OVA, but did not inhibit clinical EAMG or AChR responses. Moderate nonspecific suppression by splenic T cells from orally trated animals was demonstrated in vitro. We conclude that oral therapy is beneficial in EAMG and may prove effective in MG patients. Early priming and delayed inhibition suggest that a molecule with less immunogenic potential than intact AChR might be more effective as a therapeutic agent.
Butyrylcholinesterase reactivity differentiates the amyloid plaques of aging from those of dementia
Authors: Mesulam ‐Marsel , Geula Changiz 
Published: January 2005

AbstractIn a sample of consecutively received, 4 demented and 4 age‐matched nondemented brains, the total cortical area covered by plaque‐like Aβ amyloid and butyrylcholinesterase deposits was measured at two regions of the temporal cortex with the help of computed densitometry. Demented as well as age‐matched nondemented brains contained Aβ and butyrylcholinesterase‐positive plaques. The total cortical area covered by the Aβ precipitates was higher in demented individuals but there was overlap with the values seen in the specimens from nondemented individuals. The proportinal plaque area displaying butyrylcholinesterase reactivity was very significantly and fivefold to sixfold higher in the demented than in the nondemented group and there was no overlap between the two populations. Diffuse Aβ deposits in nondemented elderly brains may represent a benign or preclinical stage of plaque deposition with relatively little pathological effect on brain tissue and mental function. Our results suggest that the progressively more extensive butyrylcholinesterase reactivity of plaques may participate in their transformation from a relatively benign form to pathogenic structures associated with neuritic degeneration and dementia.
Very long chain fatty acids in X‐linked adrenoleukodystrophy brain after treatment with Lorenzo's oil
Authors: Poulos Alfred , Gibson Robert , Sharp Peter , Beckman Kaye , Rattan‐Smith Padraic G 
Published: January 2005

AbstractThe fatty acid composition of postmortem brain and liver from an adrenoleukodystrophy patient whose diet was supplemented with Lorenzo's oil (glycerol trioleate and glycerol trierucate) for 9 months was determined. The diet depressed plasma and liver saturated very long chain fatty acids (24:0 and 26:0) and increased plasma and liver erucic (22:1) and nervonic (24:1) acids. The levels of plasma linoleic (18:2 n‐6), eicosopentaenoic (20:5 n‐3), and docosahexaenoic (22:6 n‐3) acids were also reduced, while the biochemical marker for essential fatty acid deficiency (20:3 n‐9) was markedly increased in liver. However, we were unable to detect any corresponding changes in brain indicating that little erucic acid crossed the blood–brain barrier. Our findings suggest that dietary supplementation with Lorenzo's oil is of limited value in correcting the accumulation of saturated very long chain fatty acids in the brain of patients with adrenoleukodystrophy.
Induction of nitric oxide synthase in demyelinating regions of multiple sclerosis brains
Authors: Bö Lars , Dawson Ted M. , Wesselingh Steven , Möurk Sverre , Choi Steven , Kong Pei Ann , Hanley Daniel , Trapp Bruce D. 
Published: January 2005

AbstractThe amount of messenger RNA encoding human inducible nitric oxide synthase and the presence and distribution of NADPH diaphorase were determined in tissue sections from multiple sclerosis (MS) and control brains. Levels of human nitric oxide synthase messenger RNA were markedly elevated in MS brains when compared to normal control brains. NADPH diaphorase activity, a histochemical stain reflecting nitric oxide synthase catalytic activity, was detected in reactive astrocytes in active demyelinating MS lesions and at the edge of chronic active demyelinating lesions. Control brains did not contain NADPH diaphorase–positive astrocytes. These results implicate the free radical nitric oxide in the pathogenesis of demyelinating MS lesions.
Manganese intoxication and chronic liver failure
Authors: Hauser Robert A. , Zesiewicz Theresa A. , Rosemurgy Alexander S. , Martinez Carlos , Olanow C. W. 
Published: January 2005

AbstractManganese intoxication and chronic liver failure are associated with strikingly similar clinical, imaging, and pathological abnormalities. As manganese is primarily cleared by the liver, inadequate elimination of manganese absorbed from the normal diet may lead to manganese overload in patients with liver disease. We report a significant elevation of blood manganese concentration in 3 patients with biopsy‐proved hepatic cirrhosis who exhibited neurological dysfunction and characterstic abnormal signal hyperintensity in the globi pallidi and substantia nigra on T1‐weighted magnetic resonance imaging. We speculate that manganese accumulation in the brain accounts for the magnetic resonance imaging abnormalities and contributes to neurological dysfunction in patients with liver disease.
Histometric effects of ciliary neurotrophic factor in wobbler mouse motor neuron disease
Authors: Ikeda Ken , Wong Vivien , Holmlund Thomas H. , Greene Tom , Cedarbaum Jesse M. , Lindsay Ronald M. , Mitsumoto Hiroshi 
Published: January 2005

AbstractWe investigated the histological effects of ciliary neurotrophic factor on degenerating motor neurons, their axons, and skeletal muscles in 68 wobbler mice with motor neuron disease. Treatment consisted of recombinant rat or human ciliary neurotrophic factor (or a vehicle solution), 1‐mg/kg subcutaneous injection, three times per week for 4 weeks after the clinical diagnosis. The number of motor neurons immunoreactive for calcitonin gene‐‐related peptide was higher in mice receiving rat ciliary neurotrophic factor (p < 0.03), although the number of choline acetyltransferase‐reactive neurons was the same in both treated and untreated control groups. Treatment did not prevent vacuolar degeneration of motor neurons. In mice treated with human ciliary neurotrophic factor, the percentage of axons undergoing acute axonal degeneration (myelin ovoids) was smaller in the entire C5 ventral root (p < 0.02) and in the musculocutaneous nerve (p < 0.04), and the number of myelinated nerve fibers was 30% higher in both nerves (p < 0.01 and p < 0.04, respectively) than in controls. In ciliary neurotrophic factor‐treated mice, the biceps muscle weight was 20% greater, the mean muscle fiber diameter was 30% larger, and the number of atrophied muscle fibers was 75% lower than that in the vehicle‐treated wobbler mice (p < 0.001 for all three results). The number of terminal axonal branching points and the mean length of motor end‐plates were also higher in the ciliary neurotrophic factor‐treated mice (p < 0.001 and p < 0.02, respectively). Our study thus suggests that ciliary neurotrophic factor slowed neuronal degeneration, enhanced axonal regeneration at both the proximal and distal motor axons, and reduced muscle atrophy in this motor neuron disease.
Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy
Authors: Davie C. A. , Wenning G. K. , Barker G. J. , Tofts P. S. , Kendall B. E. , Quinn N. , McDonald W. I. , Marsden C. D. , Miller D. H. 
Published: January 2005

AbstractProton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), and 9 healthy age‐matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction in the N‐acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96–2.0; p < 0.02) compared with the NAA/creatine ratio (median, 1.82; range, 1.19–2.31; p > 0.5). The NAA/creatine ratio was markedly reduced in 6 of the SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group (median, 1.02; range, 0.91–1.23; p < 0.04) compared with the control group (median, 1.22; range, 1.05–1.65). The IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89–1.65; p = 0.25) compared with controls. The olivopontocerebellar group also showed a significant reduction in the NAA/creatine ratio from the lentiform nucleus (median, 1.47; range, 1.22–1.68; p < 0.01) compared with the controls as well as a nonsignificant reduction in the choline/creatine ratio (median, 0.93; range, 0.85–1.27; p < 0.4). In vivo quantification of absolute metabolite concentrations was possible in 7 MSA patients and 6 controls and confirmed an absolute reduction of choline‐containing compounds and NAA in the MSA group compared with controls with no significant difference in the creatine concentrations between the MSA groups probably reflects neuronal loss, occurring predominantly in the putamen. Proton magnetic resonance spectroscopy is a useful, noninvasive technique to help differentiate MSA from IPD.
A gene for hereditary paroxysmal cerebellar ataxia maps to chromosome 19p
Authors: Vahedi Katayoun , Joutel Anne , van Bogaert Patrick , Ducros Anne , Maciazeck Jacqueline , Bach Jean FrancOis , Bousser Marie Germaine , Tournier‐Lasserve Elisabeth 
Published: January 2005

AbstractHereditary paroxysmal cerebellar ataxia (HPCA) is an autosomal dominant disorder characterized by the recurrence of intermittent attacks of vestibulocerebellar ataxia lasting from 15 minutes to a few days. The number of attacks is often significantly decreased by acetazolamide treatment. Neurological examination shows a permanent gaze‐evoked nystagmus, as well as a mild cerebellar ataxia in most patients. The paroxysmal feature of this condition is shared by another autosomal dominat neurological condition, familial hemiplegic migraine (FHM), a condition in which permanent cerebellar signs have also been reported in some families. Although hemiplegic migraine has never been reported in patients with HPCA, we hypothesized, based on the latter observations, that HPCA and FHM may be allelic disorders. We previously mapped a gene responsible for FHM on the short arm of chromosome 19. We performed linkage analysis with 6 markers spanning the FHM interval on a large HPCA family. Significant lod scores were obtained with 3 markers: D19S244 (LS =; 3.71), D19S221 (3.60), and D19S226 (3.54) at theta = 0. Haplotype and multipoint linkage analysis established that the most likely location was the same interval of 30 cM encompassing the chromosome 19 FHM locus.
An allelic association study of monoamine oxidase B in parkinson's disease
Authors: Ho S. L. , Kapadi A. L. , Ramsden D. B. , Williams A. C. 
Published: January 2005

AbstractA single‐stranded conformational polymorphism in the monoamine oxidase B gene was shown to be A or G, 36 bases upstream from the intron 13‐exon 14 boundary. An allelic association study revealed no statistically significant associations between this single‐base polymorphism and Parkinson's disease, unlike the results of a previous study.
Visual system abnormalities in adrenomyeloneuropathy
Authors: Kaplan Peter W. , Kruse Bernd , Tusa Ronald J. , Shankroff Jan , Rignani Joellen , Moser Hugo W. 
Published: January 2005

AbstractWe studied the visual system in 59 men with adrenomyeloneuropathy. Pattern‐reversal visual evoked potentials, magnetic resonance imaging, and clinical examination revealed that visual pathways are affected in 63% of patients, involving the optic discs, optic nerves, lateral geniculate bodies, optic radiations, and parietooccipital cortex. This indicates both primary demyelination of the optic nerves and discs, and more diffuse involvement of postchiasmal structures.
Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy
Authors: Rinne J. O. , Burn D. J. , Dphil C. J. Mathias , Quinn N. P. , Marsden C. D. , Brooks D. J. 
Published: January 2005

AbstractTen patients with sporadic olivopontocerebellar atrophy and autonomic failure were studied with positron emission tomography. Subjects underwent both an {11C}diprenorphine and an {18F}fluorodopa scan. The mean caudateoccipital uptake ratio for {11C}diprenorphine was significantly reduced to 88% and the putamen‐occipital uptake ratio to 85% of the control values. Individually, 4 of the 10 patients had significantly reduced opioid binding in the putamen. Mean putamen {18F}fluorodopa uptake was significantly diminished (to 71% of the control mean); individually 7 patients had significantly reduced uptake. There was a significant positive correlation between putamen‐occipital uptake ratios for {11C}diprenorphine and putamen uptake of {18F}fluorodopa. Our results suggest that subclinical nigrostriatal dysfunction is present in the majority of patients with sporadic olivopontocerebellar atrophy, in accordance with it being part of the spectrum of multiple system atrophy.
Dentatorubral‐pallidoluysian atrophy: Clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat
Authors: Ikeuchi Takeshi , Koide Reiji , Tanaka Hajime , Onodera Osamu , Igarashi Shuichi , Takahashi Hitoshi , Kondo Rui , Ishikawa Atsushi , Tomoda Akemi , Miike Teruhisa , Keiko Sato  , Ihara Yuetsu , Hayabara Toshiyuki , Isa Fumiko , Tanabe Hitoshi , Tokiguchi Susumu , Hayashi Masataka , Shimizu Natsue , Ikuta Fusahiro , Naito Haruhiko , Tsuji Shoji 
Published: January 2005

AbstractDentatorubral‐pallidoluysian atrophy is an autosomal dominant neurodegenerative disease characterized by various combinations of ataxia, choreoathetosis, myoclonus, epilepsy, and dementia as well as a wide range of ages at onset. A specific unstable trinucleotide repeat expansion in a gene on the short arm of chromosome 12 was recently identified as the pathogenic mutation for this disease. We investigated how the degree of expansion of the CAG repeat affects the clinical manifestations of dentatorubral‐pallidoluysian atrophy. The size of the expanded alleles was well correlated with the age at onset (r = ‐0.696, p < 0.001). Patients with the progressive myoclonus epilepsy phenotype had larger expansions (62‐79 repeats) and an earlier age at onset (onset before age 21). Furthermore, most of the patients with the progressive myoclonus epilepsy phenotype inherited their expanded alleles from their affected fathers. On the other hand, patients with the non‐progressive myoclonus epilepsy phenotype showed smaller expansions (54‐67 repeats) and a later age at onset (onset at or after age 21). Detailed analyses of clinical features demonstrated that ataxia, involuntary movement of either myoclonus or choreoathetosis, and intellectual decline are cardinal features of dentatorubral‐pallidoluysian atrophy, with myoclonus and epilepsy being observed more frequently in patients with an earlier age at onset. Thus the wide variation in clinical manifestations of dentatorubral‐pallidoluysian atrophy can now be clearly explained based on the degree of CAG repeat expansion, which strongly indicates that the expanded alleles are intimately involved in the neuronal degeneration in dentatofugal and pallidofugal systems.