bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia
Authors: Browne Susan E. , Bowling Allen C. , Macgarvey Usha , Baik M. Jay , Berger Stephanie C. , Muquit Miratul M. K. , Bird Edward D. , Beal M. Flint 
Published: January 2005

AbstractThe etiology of the selective neuronal death that occurs in Huntington's disease (HD) is unknown. Several lines of evidence implicate the involvement of energetic defects and oxidative damage in the disease process, including a recent study that demonstrated an interaction between huntingtin protein and the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). Using spectrophotometric assays in postmortem brain tissue, we found evidence of impaired oxidative phosphorylation enzyme activities restricted to the basal ganglia in HD brain, while enzyme activities were unaltered in three regions relatively spared by HD pathology (frontal cortex, parietal cortex, and cerebellum). Citrate synthase‐corrected complex II‐III activity was markedly reduced in both HD caudate (−29%) and putamen (−67%), and complex IV activity was reduced in HD putamen (−62%). Complex I and GAPDH activities were unaltered in all regions examined. We also measured levels of the oxidative damage product 8‐hydroxydeoxyguanosine (OH8dG) in nuclear DNA, and superoxide dismutase (SOD) activity. OH8dG levels were significantly increased in HD caudate. Cytosolic SOD activity was slightly reduced in HD parietal cortex and cerebellum, whereas particulate SOD activity was unaltered in these regions. These results further support a role for metabolic dysfunction and oxidative damage in the pathogenesis of HD.
Allelic heterogeneity of mediterranean myoclonus and the cystatin B gene
Authors: Labauge Pierre , Ouazzani RÉDa , M'Rabet Amel , Grid Djamel , Genton Pierre , Dravet Charlotte , Chkili Taieb , Beck Corrine , Buresi Catherine , Baldy‐Moulinier Michel , Malafosse Alain 
Published: January 2005

AbstractMediterranean myoclonus is a progressive myoclonus epilepsy with autosomal recessive inheritance. Anothe form has been described in Finland, the so‐called Baltic myoclonus. Mediterranean myoclonus and Baltic myoclonus are also known as Unverricht‐Lundborg disease. Linkage analyses have shown that the genes for both these forms of myoclonus are closely linked to 21q22.3 DNA markers, suggesting that they are caused by mutations at the same locus (EPM1). Recently, two heterozygous mutations were found in the cystatin B gene in patients with Unverricht‐Lundborg disease. We report recombinational and linkage disequilibrium mapping of EPM1, and cystatin B gene sequencing, in 14 consanguineous pedigrees with Mediterranean myoclonus. Linkage to 21q22.3 DNA markers was observed in all these families. Haplotype analysis suggests that a common mutation segregates within these pedigrees, and that this mutation is different from the common one responsible for the Finnish form of Unverricht‐Lundborg disease. No mutation was found in the exons or splice junctions of the cystatin B gene in the 14 pedigrees.
CAG repeat number governs the development rate of pathology in Huntington's disease
Authors: Penney John B. , Vonsattel Jean‐Paul , Macdonald Marcy E. , Gusella James F. , Myers Richard H. 
Published: January 2005

AbstractWe compared the number of CAG repeats, the age at death, and the severity of neuropathology in 89 Huntington's disease brains. We found a linear correlation between the CAG repeat number and the quotient of the degree of atrophy in the striatum (the brain region most severely affected in Huntington's disease) divided by age at death, with an intercept at 35.5 repeats. The largest CAG repeat length, therefore, at which no pathology is expected to develop is 35.5. These results imply that striatal damage in Huntington's disease is almost entirely a lineaar function of the length of the polyglutamine stretch beyond 35.5 glutamines multiplied by the age of the patient. Thus, it is predicted that the pathological process develops linearly from birth. Analysis of other measures of striatal function could test this hypothesis and might determine when treatment for CAG repeat diseases should start.
Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease
Authors: Minoshima Saroshi , Giordani Bruno , Berent Stanley , Frey Kirk A. , Foster Norman L. , Kuhl David E. 
Published: January 2005

AbstractThis study investigated cerebral glucose metabolism in very early Alzheimer's disease, before a clinical diagnosis of probable Alzheimer's disease is possible, using [18F]fluorodeoxyglucose positron emission tomography. First, 66 patients with probable Alzheimer's disease with a spectrum of dementia severity (Mini‐Mental State Examination score, 0–23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three‐dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini‐Mental State Examination score, 25 · 1) at the time of scanning but whose condition later progressed to probable Alzheimer's disease. Both results were compared to cerebral metabolic activity in 22 age‐similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21–22%) in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer's disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer's disease.
Early‐onset Alzheimer's disease with a presenilin‐1 mutation at the site corresponding to the volga German presenilin‐2 mutation
Authors: Crook Richard , Ellis Ronald , Shanks Megan , Thal Leon J. , Perez‐Tur Jordi , Baker Matt , Hutton Mike , Haltia Tuomas , Hardy John , Galasko Douglas 
Published: January 2005

AbstractWe describe a new mutation causing Alzheimer's disease (AD) in presenilin‐1 (N135D) that is at the homologous site to the presenilin 2 mutation (N141I) in Volga German kindreds. The phenotype of PS1 N135D is an early‐onset (34–38 years) disease. The mutation forms part of, and extends, the α‐helical array of mutations in transmembrane 2 of the presenilins and leads to the suggestion that disruption of this helical face is the molecular insult that leads to disease.
X‐linked emery‐dreifuss muscular dystrophy can be diagnosed from skin biopsy or blood sample
Authors: Mora M. , Cartegni L. , Di Blasi C. , Barresi R. , Bione S. , di Barletta M. Raffaele , Morandi L. , Merlini L. , Nigro V. , Politano L. , Donati M. A. , Cornelio F. , Cobianchi F. , Toniolo D. 
Published: January 2005

AbstractWe have raised an anti‐emerin polyclonal antibody against a fusion protein encompassing most of the hydrophilic portion of emerin. Using this antibody, we have analyzed emerin expression in Emery‐Dreifuss muscular dystrophy (EDMD) patients and controls, by immunocytochemistry, in peripheral blood mononuclear cells and lymphoblasts. Emerin was localized on the surfaces of nuclei in control skeletal muscle and skin but was absent or reduced in patient skeletal muscle, was absent from the skin of patients, and was expressed only in a few nuclei in a patient's mother. Immunoblot of peripheral blood cells from EDMD patients showed absence of the emerin band, altered‐size emerin, or a protein of normal molecular mass but slightly reduced quantity. The diagnosis of X‐linked EDMD is normally confirmed by genegic analysis of the STA gene coding for emerin. We propose immunocytochemical evaluation of emerin expression in skin biopsies as a sensitive and more convenient tool for diagnosing X‐linked EDMD and, in particular, for distinguishing it from the autosomal dominant form. This technique may be applied to suspected EDMD patients, especially sporadic cases or those with incomplete clinical phenotype, and also suspected carriers. Immunoblot of peripheral blood cells is also useful, but it may not unequivocally identify carriers and some patients.
Hypoxia—ischemia causes abnormalities in glutamate transporters and death of astroglia and neurons in newborn striatum
Authors: Martin Lee J. , Brambrink Ansgar M. , Lehmann Christoph , Portera‐Cailliau Carlos , Koehler Raymond , Rothstein Jeffrey , Traystman Richard J. 
Published: January 2005

AbstractThe neonatal striatum degenerates after hypoxia–ischemia (H‐I). We tested the hypothesis that damage to astrocytes and loss of glutamate transporters accompany striatal neurodegeneration after H‐I. Newborn piglets were subjected to 30 minutes of hypoxia (arterial O2 saturation, 30%) and then 7 minutes of airway occlusion (O2 saturation, 5%), producing cardiac arrest, followed by cardiopulmonary resuscitation. Piglets recovered for 24, 48, or 96 hours. At 24 hours, 66% of putaminal neurons were injured, without differing significantly thereafter, but neuronal densities were reduced progressively (21–44%). By DNA nick‐end labeling, the number of dying putaminal cells per square millimeter was increased maximally at 24 to 48 hours. Glial fibrillary acidic protein–positive cell body densities were reduced 48 to 55% at 24 to 48 hours but then recovered by 96 hours. Early postischemia, subsets of astrocytes had fragmented DNA; later postischemia, subsets of astrocytes proliferated. By immunocytochemistry, glutamate transporter 1 (GLT1) was lost after ischemia in the astroglial compartment but gained in cells appearing as neurons, whereas neuronal excitatory amino acid carrier 1 (EAAC1) dissipated. By immunoblotting, GLT1 and EAAC1 levels were 85% and 45% of control, respectively, at 24 hours of recovery. Thus, astroglial and neuronal injury occurs rapidly in H‐I newborn striatum, with early gliodegeneration and glutamate transporter abnormalities possibly contributing to neurodegeneration.
Short‐ and long‐duration responses to levodopa during the first year of levodopa therapy
Authors: Nutt John G. , Carter Julie H. , Van Houten Laura , Woodward William R. 
Published: January 2005

AbstractWe examined the response to 2–hour levodopa infusions in 18 Parkinson's disease subjects before starting long‐term levodopa treatment and after 6 and 12 months of treatment using tapping speed as an index of bradykinesia. The long‐duration response (LDR), measured as the increase in baseline (overnight without levodopa) tapping speed, increased by 29 ± 18 at 6 months and by 35 ± 24 at 12 months. The magnitude of the short‐duration response (SDR) to a 2‐hour levodopa infusion after an overnight levodopa withdrawal did not differ at 6 and 12 months (16 ± 18 and 20±13 taps/min) from that before long‐term levodopa (21±taps/min). However, when levodopa was withheld for 3 days, it was evident that the SDR magnitude was increasing in magnitude (19, 23, and 31 taps/min at 0, 6, and 12 months). Duration of SDR did not change. A diurnal motor pattern with faster tapping speeds in the morning and slower in the evening was apparent on the days no levodopa was administered. These observations indicate (1) the LDR is responsible for much of the sustained response to levodopa during the first year of treatment, (2) the SDR magnitude increases but is obscured by the LDR, and (3) a diurnal pattern of motor function is present that may be partially responsible for the poorer motor function in the afternoons and evenings.
Increased 3‐nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis
Authors: Beal M. Flint , Ferrante Robert J. , Browne Susan E. , Matthews Russell T. , Kowall Neil W. , Brown Robert H. 
Published: January 2005

AbstractThe pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3‐Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3‐nitrotyrosine and 3‐nitro‐4‐hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3‐nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3‐nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite‐mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.
Inflammatory central nervous system demyelination: Correlation of magnetic resonance imaging findings with lesion pathology
Authors: Brück Wolfgang , Bitsch Andreas , Kolenda Herbert , Brück Yvonne , Stiefel Michael , Lassmann Hans 
Published: January 2005

AbstractMagnetic resonance imaging (MRI) is widely used to evaluate and monitor disease activity in inflammatory demyelinating central nervous system (CNS) diseases such as multiple sclerosis. The present study aimed at correlating MRI findings with histological parameters in 6 cases of biopsy‐proven inflammatory demyelination of the CNS. The earliest stages of demyelinating activity manifested as almost isointense lesions with a massive gadolinium‐DTPA (Gd‐DTPA) enhancement in T1‐weighted scans. In T2‐weighted scans, early active lesions formed a border of decreased intensity compared with the lesion center and the perifocal edema. The morphological correlate of this pattern in our patients was activated macrophages in the zone of myelin destruction at the plaque border. Late active lesions were hypointense in T1 and hyperintense in T2 scans. Inactive demyelinated and remyelinating lesions were hyperintense in T2 scans and enhanced inhomogenously after Gd‐DTPA application. T1 scans revealed major differences in the degree of hypointensity that correlated with the extent of axonal damage, extracellular edema, and the degree of demyelination or remyelination.
Inhibition of axonal growth from sensory neurons by excess nerve growth factor
Authors: Conti Anna M. , Fischer Stephanie J. , Windebank Anthony J. 
Published: January 2005

AbstractFifteen‐day embryonic rat dorsal root ganglion (DRG) neurons were exposed to 1 to 200 ng/ml nerve growth factor (NFG). Maximal neurite outgrowth was obtained with 10 to 20 ng/ml. Neurite outgrowth was reduced to 89% of maximal by increasing NGF to 50 ng/ml, to 66% by 100 ng/ml, and to 18% by 200 ng/ml NGF. Identical effects were seen with mouse 2.5S NGF and recombinant human NGF. Neuron cell counts demonstrated that significant cell death did not occur. In time course experiments, significant inhibition, compared with control, began within 1 hour of adding 200 ng/ml and 3 hours of adding 50 ng/ml NGF. The inhibitory effect of NGF on neurite outgrowth was reversed within 3 hours when DRG were incubated with 5 ng/ml NGF after treatment with 50 or 200 ng/ml NGF medium for 12 hours. The inhibition demonstrated for neurons did not occur in PC12 cells; axonal growth was not inhibited by up to 1,000 ng/ml NGF. Excess brain‐derived neurotrophic factor or neurotrophin‐3 did not inhibit neurite outgrowth. We conclude that high concentrations of NGF produces specific and reversible arrest of neurite outgrowth from sensory neurons. This observation has important clinical implications, because these inhibitory concentrations have been exceeded when NGF has been administered into the central nervous system of humans and animals.
Association of IgM type anti‐GM1 antibodies and muscle strength in chronic acquired demylelinating polyneuropathy
Authors: Bech Einar , Andersen Henning , Ørntoft Torben F. , Jakobsen Johannes 
Published: January 2005

AbstractThe pathogenetic role of anti‐GM1 in chronic acquired demyelinating polyneuropathy (CADP) is uncertain. An association between antibodies and disease activity has not yet been established. In 8 patients with CADP followed longitudinally, anti‐GM1 antibodies were monitored with a standardized enzyme‐linked immunosorbent assay technique and muscle performance with isokinetic dynamometry. During a mean observation period of 24 months, strength improved in 6 of 8 patients by a median value of 54.5%, and anti‐GM1 fell in all 6 patients; the reduction being 43%. In 2 patients, muscle performance deteriorated by 30 and 8%, whereas anti‐GM1 titers increased by 10 and 9%, respectively. The relative change in anti‐GM1 was inversely related to muscle performance. Clinical scoring of muscle performance according to the Medical Research Council scale failed to show an association with anti‐GM1. It is concluded that anti‐GM1 antibodies are closely realted to disease activity, and that the close association indicates a role of anti‐GM1 in the pathogenesis of CADP.
Diffusion‐weighted MRI in transient global amnesia: Elevated signal intensity in the left mesial temporal lobe in 7 of 10 patients
Authors: Strupp Michael , Brüning Roland , Wu Ren Hua , Deimling Michael , Reiser Maximilian , Brandt Thomas 
Published: January 2005

AbstractPrompted by the findings of previous studies with positron emission tomography and single photon emission computed tomography, which demonstrated hypoperfusion or hyperperfusion in the left temporal lobe in isolated patients with transient global amnesia (TGA), we compared the sensitivity of diffusion‐weighted (DW) magnetic resonance imaging (MRI) with that of conventional T1‐ and T2‐weighted MRI in patients with TGA. Ten patients with the typical syndrome of a pure TGA were included in the study. For all patients, a coronal DW sequence, a steady‐state free precession (SSFP) sequence, and conventional T1‐ and T2‐weighted turbo spin‐echo sequences were obtained. Seven of the 10 patients had elevated signal intensity in the left hippocampal region on DW MRI; moreover, 3 of these 7 patients exhibited bilateral signal abnormality in this sequence. All conventional T1‐ and T2‐ weighted images as well as all follow‐up studies were normal. The signal elevation in DW MRI correlates with a decrease in the interstitial space and with cellular edema in the temporal lobe during TGA. The underlying pathomechanism causing this cellular edema cannot be clearly outlined using DW MRI. Our data are, however, compatible with spreading depression. This is the first study to show that DW MRI is a sensitive MRI method for evaluating TGA, especially in the early stage of the disease.
Progressive atrophy of cerebellum and brainstem as a function of age and the size of the expanded CAG repeats in the MJD1 gene in Machado‐Joseph disease
Authors: Onodera Osamu , Idezuka Jiro , Igarashi Shuichi , Takiyama Yoshihisa , Endo Kotaro , Takano Hiroki , Oyake Mutsuo , Tanaka Hajime , Inuzuka Takashi , Hayashi Tsunemi , Yuasa Tatsuhiko , Ito Jusuke , Miyatake Tadashi , Tsuji Shoji 
Published: January 2005

AbstractMachado‐Joseph disease (MJD) is an autosomal dominat neurodegenerative disease characterized by cerebellar ataxia associated to varying degrees with pyramidal signs, extrapyramidal signs, or peripheral amyotrophy. It is caused by unstable expansion of the CAG repeat in the MJD1 gene on chromosome 14q32.1. To determine how the neurodegenerative process in the central nervous system of patients with MJD correlates with the size of expanded CAG repeats in the MJD1 gene and other factors, we performed detailed quantitative analyses of findings of magnetic resonance imaging of the central nervous system of 21 patients with MJD of various ages and with various sizes of expanded CAG repeats. We found that atrophy of the brainstem and cerebellar vermis in MJD patients is closely correlated not only with the size of expanded CAG repeat in the MJD1 gene but also with patient age, which suggests that the neurodegenerative process in MJD is regulated by the size of expanded CAG repeats as well as by the patient age.
Increased sensitivity of fibroblasts from amyotrophic lateral sclerosis patients to oxidative stress
Authors: Aguirre T. , van Den Bosch L. , Goetschalckx K. , Tilkin P. , Mathijis G. , Cassiman J. J. , Robberecht W. 
Published: January 2005

AbstractAlthough the cause of amyotrophic lateral sclerosis (ALS) is unkown, free radical toxicity is thought to play a pathogenic role. We investigated whether cells from ALS patients are more vulnerable to exogenously induced oxidative stress than cells from controls. We therefore studied the sensitivity of fibroblasts from patients with sporadic ALS (SALS), and from patients with familial ALS (FALS) associated with copper/zinc superoxide dismutase (Cu/ZnSOD) mutations (SOD1‐FALS), to the free radical‐generating agents 3‐morpholinosydnonimine (SIN‐1) and hydrogen peroxide (H2O2), and to serum withdrawal. SOD1‐FALS and SALS fibroblasts were significantly more sensitive than controls to SIN‐1 but not to serum withdrawal. In addition, SOD1‐FALS fibroblasts were more sensitive to H2O2 than SALS fibroblasts and than fibroblasts of controls. These results suggest that the mechanism underlying both SOD1‐FALS and SALS jeopardizes the cell's defense against free radical stress, and that SOD1‐FALS cells are particularly sensitive to H2O2. The latter finding is compatible with biochemical data on the increased affinity of the mutated Cu/ZnSOD for H2O2.
Paroxysmal tonic upgaze: A reappraisal of outcome
Authors: Hayman M. , Harvey A. S. , Hopkins I. J. , Kornberg A. J. , Coleman L. T. , Shield L. K. 
Published: January 2005

AbstractParoxysmal tonic upgaze (PTU) of childhood is a distinctive neuro‐ophthalmological syndrome of unknown etiology and pathogenesis that is characterized by episodes of sustained upward deviation of the eyes, often with incomplete downward saccades on attempted downgaze. It is generally regarded as having a benign outcome. We observed 16 children with PTU, from 10 months to 11 years from onset (mean, 5.4 years), to study the natural history and possible etiology. Five cases were from two unrelated families. Onset of PTU occurred either during or after an intercurrent infection or vaccination in 5 children. No antecedent was identifiable in the rest. PTU had completely resolved in 10 children (62%) (mean age at offset, 2.5 years), whereas 2 children intermittently manifest a modified from of the disorder. At follow‐up, 11 children (69%) had developmental delay, intellectual disability, or language delay and 9 (56%) had ocular motility problems other than PTU. Only 3 children (19%) had normal development and neurological findings. PTU is a heterogeneous syndrome with respect to associations and outcome and may simply be an age‐dependent manifestation of a variety of disorders affecting corticomesencephalic control of vertical eye movement. This disorder may be an early sign of more widespread neurological dysfunction.
Optic neuritis heralding varicella zoster virus retinitis in a patient with acquired immunodeficiency syndrome
Authors: Meenken Christina , van Den Horn Gerardus J. , de Smet Marc D. , van Der Meer Jan T. M. 
Published: January 2005

AbstractWe report on a 29‐year‐old severely compromised acquired immunodeficiency syndrome patient who developed retrobulbar optic neuritis 5 weeks after an episode of cutaneous herpes zoster infection. During the optic neuritis, varicella zoster virus could be demonstrated in the cerebrospinal fluid. The neuritis responded well to treatment with foscarnet, but, 3 weeks into therapy, varicella zoster retinitis developed. Additional treatment with intravenous acyclovir stopped progression of the retinitis and resulted in healing of the retinal lesions. This case suggests that retrobulbar optic neuritis can be regarded as a prodrome of imminent acute retinal necrosis. Early recognition and prompt therapy with combined antivirals may prevent the development of this devastating ocular complication of varicella zoster infection.