bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of tuberin from cerebral tissues with tuberous sclerosis and astrocytoma
Authors: Mizuguchi Masashi , Kato Mitsuhiro , Yamanouchi Hideo , Ikeda Kazuhiko , Takashima Sachio 
Published: January 2005

AbstractWe studied the expression of tuberin, the TSC2 gene product, in cerebra with or without tuberous sclerosis. Tuberin was abundant in the gray matter of normal cerebra, but was undetectable in the subependymal astrocytomas from 3 patients with tuberous sclerosis. In 1 patient, cortical tubers and normally appearing cortical tissue also showed a marked loss of tuberin. These results indicate the critical role of tuberin in the neuropathology of tuberous sclerosis.
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Authors: Gómez‐Isla Teresa , Hollister Richard , West Howard , Mui Stina , Growdon John H. , Petersen Ronald C. , Parisi Joseph E. , Hyman Bradley T. 
Published: January 2005

AbstractTo assess the relationship between dementia, neuronal loss, and neuropathological findings in Alzheimer's disease (AD), we counted the number of neurons, senile plaques, and neurofibrillary tangles in a high‐order association cortex. We studied the superior temporal sulcus of 34 individuals with AD and 17 nondemented control subjects, using statistically unbiased, stereological counting techniques. The number of superior temporal sulcus neurons in nondemented control subjects was stable across the sixth to ninth decades. In AD, more than 50% of the neurons were lost. Both neuronal loss and neurofibrillary tangles increased in parallel with the duration and severity of illness, but the amount of neuronal loss exceeded by manyfold the amount of neurofibrillary tangles accumulated. In contrast to the correlation between neurofibrillary tangels and neuronal loss, the number of senile plaques and the percentage of the superior temporal sulcus that was covered by Aβ (amyloid burden) were not related to neuronal loss, number of neurofibrillary tangles, or duration of disease. Neither the amount nor the rate of neuronal loss in the superior temporal sulcus in AD correlated with apolipoprotein E genotype. These data suggest that neuronal loss in association areas such as the superior temporal sulcus contributes directly to cognitive impairment in AD.
The Role of MRI in clinical trials of multiple sclerosis: Comparison of image processing techniques
Authors: Evans A. C. , Frank J. A. , Antel J. , Miller D. H. 
Published: January 2005

AbstractMagnetic resonance imaging (MRI) has received considerable attention in recent years its potential for providing indics of multiple sclerosis activity and progression in clinical trials of new pharmaceuticals. The percieved advantages of MRI‐derived measurements include greather objectivity, sensitivity, and reproducibility when compared with clinical rating scales. Clinical scales are also somewhat biased toward lesions affecting locomotion. However, the myriad permutations of MRI acquisition parameters, analysis methodologies, and disease indices demand careful cosideration when employing MRI. Moreover, the use of MRI in research into the basic mechanisms of a disease may have different requirements than its use in a clinical trial setting. Consequently, a conference was held, sponsored by the US and Canadian multiple sclerosis societies, to review the present status of various MRI processing strategies and their potential role in clinical trials. Thirteen labortories from North America and Europe as well as regulatory agencies and statistical condultants made formal presentations followed by extended discussion. This report presents the conclusions reached and recommendations for further action that emerged from the meeting.
Deletion and conversion in spinal muscular atrophy patients: Is there a relationship to severity?
Authors: Didonato Christine J. , Ingraham Susan E. , Mendell Jerry R. , Prior Thomas W. , Lenard Sharon , Moxley Richard T. , Florence Julaine , Burghes Arthur H. M. 
Published: January 2005

AbstractThe spinal muscular atrophy—determining gene, survival motor neuron (SMN), is present in two copies, telSMN and cenSMN, which can be distinguished by base‐pair changes in exons 7 and 8. The telSMN gene is often absent in spinal muscular atrophy patients, which could be due to deletion or sequence conversion (telSMN conversion to cenSMN giving rise to two cenSMN genes). To test for conversion events in spinal muscular atrophy, we amplified a 1‐kb fragment that spanned exons 7 and 8 of SMN from 5 patients who retained telSMN exon 8 but lacked exon 7. In all patients, sequence analysis demonstrated that cenSMN exon 7 was adjacent to telSMN exon 8, indicating conversion. All 5 patients with this mutation had type II or III spinal muscular atrophy, strongly supporting an association with chronic spinal muscular atrophy. We also identified 3 families in which 2 siblings had no detectable telSMN but presented with markedly different phenotypes. We suggest that sequence conversion is a common event in spinal muscular atrophy and is associated with the milder form of the disease. The severity, however, can be modified in either a positive or negative direction by other factors that influence splicing or expression of the sequence converted SMN gene.
A novel mitochondrial tRNA phenylalanine mutation presenting with acute rhabdomyolysis
Authors: Chinnery P. F. , Johnson M. A. , Taylor R. W. , Lightowlers R. N. , Turnbull D. M. 
Published: January 2005

AbstractWe describe a patient who presented with acute rhabdomyolysis and had 68% cytochrome c oxidase (COX)‐deficient fibers in skeletal muscle. Further investigations confirmed a respiratory chain defect that was associated with a novel heteroplasmic point mutation in the phenylalanine tRNA gene of the mitochondrial genome (mtDNA). Analysis of single muscle fibers revealed a significantly greater level of mutant mtDNA in COX‐negative fibers. This is the first case of a mitochondrial tRNA gene point mutation presenting with acute rhabdomyolysis and recurrent myoglobinuria.
Acetylcholine receptor expression in human extraocular muscles and their susceptibility to myasthenia gravis
Authors: MacLennan C. , Beeson D. , Buijs A.‐M. , Vincent A. , Newsom‐Davis J. 
Published: January 2005

AbstractIn myasthenia gravis (MG), extraocular muscle (EOM) weakness is often an initial and persisting symptom. It has been proposed that acetylcholine receptor (AChR) from EOM is antigenically different from AChR of other innervated muscles and that the presence of antibodies to fetal AChR expressed in EOM causes their weakness. We have (1) studied mRNA expression for each of the AChR subunits (α, β, γ, δ, and ϵ) in human muscle, including EOM, and (2) compared the binding of sera from ocular myasthenia gravis (OMG) patients with fetal (α2βγδ) and adult (α2βϵδ) human AChRs. RNase protection assays showed that expression of the AChR γ‐subunit (fetal‐type) mRNA in EOM was comparable with that in other innervated muscle types. By contrast, ϵ‐subunit (adult‐type) mRNA was expressed at much higher levels in EOM than in other muscles studied. Moreover, some OMG sera bound specifically to adult AChR. These results do not support the contention that susceptibility of EOM in MG results from expression of fetal AChR and indicate that the inclusion of antigen from a source rich in adult AChR in the MG diagnostic assay will increase the yield of positive results in OMG patients.
Gene locus for autosomal recessive distal myopathy with rimmed vacuoles maps to chromosome 9
Authors: Ikeuchi Takeshi , Asaka Tomoya , Saito Masaaki , Tanaka Hajime , Higuchi Sari , Tanaka Keiko , Saida Kyoko , Uyama Eiichiro , Mizusawa Hidenobu , Fukuhara Nobuyoshi , Nonaka Ikuya , Takamori Masaharu , Tsuji Shoji 
Published: January 2005

AbstractDistal myopathy with rimmed vacuoles is an autosomal recessive muscular disorder, characterized clinically by weakness of the distal muscles in the lower limbs in early adulthood. Recently, the gene locus for familial vacuolar myopathy with autosomal recessive inheritance (hereditary inclusion body myopathy) was mapped to chromosome 9 by genome‐wide linkage analysis of nine Persian‐Jewish families. Since both disease conditions share similar clinical, genetic, and histopathological features, we analyzed seven families with distal myopathy with rimmed vacuoles using ten microsatellite markers within the region of the hereditary inclusion body myopathy locus. Significantly high cumulative pairwise lod scores were obtained with three markers: D9S248 (Zmax = 5.90 at Θ = 0), D9S43 (Zmax = 5.25 at Θ = 0), and D9S50 (Zmax = 4.23 at Θ = 0). Detection of obligate recombination events as well as multipoint linkage analysis revealed that the most likely location of the distal myopathy with rimmed vacuoles gene is in a 23.3‐cM interval defined by D9S319 and D9S276 on chromosome 9. The results raise the possibility that distal myopathy with rimmed vacuoles and hereditary inclusio body myopathy in Persian Jews are allelic diseases.
A familial syndrome of congenital cataract, mental impairment, and dentate gyrus atrophy
Authors: Hudson Arthur J. , Munoz David G. 
Published: January 2005

AbstractWe present a family with congenital cataract with, in some cases, mental retardation and emotional instability, but intellectual deterioration in all affected members. The latter was accompanied by psychosis in some. The inheritance is most likely autosomal dominant, affecting two generations and consisting of a congenitally blind parent and 6 of 11 of her offspring. In addition to these features, some affected individuals had dysphagia and movement disorder, especially choreiform movements. They all showed small body mass, due possibly to poor nutrition from dysphagia. The pathological findings were unique, demonstrating selective atrophy of the granule cell layer of the dentate gyrus. There was selective expression in paraffin‐embedded sections of αB‐crystallin (CRYA2) in oligodendroglia in all areas of the nervous system examined. αB‐Crystallin is a major optic lens protein but also a heat shock protein and molecular chaperone found in brain and a number of other tissues. Because of the association of congenital cataract and the accumulation in oligodendroglia of αB‐crystallin, the gene for this protein was sequenced for possible mutation. No mutation was found indicating other genetic locus. This family appears to have a newly recognized genetic disorder.
Clinical utility of diffusion‐weighted magnetic resonance imaging in the assessment of ischemic stroke
Authors: Lutsep H. L. , Albers G. W. , Decrespigny A. , Kamat G. N. , Marks M. P. , Moseley M. E. 
Published: January 2005

AbstractDiffusion‐weighted imaging (DWI) detects small changes in water diffusion that occur in ischemic brain. This study evaluated the clinical usefulness of a phase‐navigated spin‐echo DWI sequence compared with T2‐weighted magnetic resonance imaging (T2W MRI) in patients with cerebral ischemia and assessed apparent diffusion coefficient (ADC) and T2‐weighted imaging (T2WI) changes over time. ADC values and T2 ratios of image intensity were measured from the region of ischemia and from the corresponding contralateral brain region. The clinical histories of patients with DWI scans obtained over the course of 1 year were reviewed to ascertain whether DWI aided in clinical diagnosis or management. Of 103 scans obtained a mean of 10.4 days after symptom onset, DWI detected six lesions not seen on T2WI and discriminated two new infarcts from old lesions. DWI was most useful within 48 hours of the ictus. The evolution of ADC values and T2 ratios was evaluated in 26 cases with known symptom onset times. ADC values were low at less than 1 week after stroke onset and became elevated at chronic time points. T2 ratios were near normal acutely, increasing thereafter. DWI was superior to T2W MRI in detecting acute stroke, whereas both techniques assisted in determining lesion age.
Altered intrathymic T‐cell repertoire in human myasthenia gravis
Authors: Truffault Frédérique , Cohen‐Kaminsky Sylvia , Khalil Iman , Levasseur Philippe , Berrih‐Aknin Sonia 
Published: January 2005

AbstractIn myasthenia gravis, the thymus is thought to be the primary site of autosensitization. We investigated the Vβ T‐cell repertoire at different intrathymic differentiation stages in 17 patients with myasthenia gravis and 8 age‐matched control subjects by tricolor immunofluorescence, using a panel of six anti‐Vβ antibodies. We observed an increased expression of Vβ5.1 and Vβ8 subfamilies in the patients compared to the control subjects. These increases were observed not only in mature cells but also in the latest thymic precursors of mature cells (double‐positive CD3 high), while there was no change in intermediate precursors (double‐positive CD3 low), pointing to biased selection during intrathymic differentiation. In addition, there was a strong correlation between the percentage of Vβ5.1+ and Vβ8+ cells among both the CD4 and CD8 subsets in the patients, but not in control subjects, suggesting that thymic events relevant to the disease lead to these selected populations. Finally, location studies of Vβ5.1+ cells on thymic sections indicated that these cells were overrepresented both in the core of germinal centers and in perifollicular areas of hyperplastic thymuses, suggesting a role in the autoimmune response. Taken together, these findings are compatible with the hypothesis of a biased intrathymic selection in myasthenia gravis.
Presenilin‐1 protein expression in familial and sporadic Alzheimer's disease
Authors: Levey Allan I. , Heilman Craig J. , Lah James J. , Nash Norman R. , Rees Howard D. , Wakai Masakazu , Mirra Suzanne S. , Rye David B. , Nochlin David , Bird Thomas D. , Mufson Elliott J. 
Published: January 2005

AbstractMutations of the presenilin PS1 and PS2 genes are closely linked to aggressive forms of early‐onset (<60 years) familial Alzheimer's disease. A highly specific monoclonal antibody was developed to identify and characterize the native PS1 protein. Western blot analyses revealed a predominant 32‐kd immunoreactive polypeptide in a variety of samples, including PC12 cells transfected with human PS1 complementary DNA, brain biopsy specimens from demented patients, and postmortem samples of frontal neocortex from early‐onset familial Alzheimer's disease cases (PS1 and PS2), lateonset sporadic Alzheimer's disease cases, and cases of other degenerative disorders. This truncated polypeptide contains the N‐terminus of PS1 and appeared unchaged across cases. In 2 early‐onset cases linked to missense mutations in the PS1 gene, a PS1 immunoreactive protein (∼49 kd) accumulated in the frontal cortex. This protein was similar in size to full‐length PS1 protein present in transfected cells overexpressing PS1 complementary DNA, and in lymphocytes from an affected individual with a deletion of exon 9 of the PS1 gene, suggesting that mutations of the PS1 gene perturb the endoproteolytic processing of the protein. Immunohistochemical studies of control brains revealed that PS1 is expressed primarily in neurons, with the protein localized in the soma and dendritic processes. In contrast, PS1 showed striking localization to the neuropathology in early‐onset familial Alzheimer's disease and sporadic Alzheimer's disease cases. PS1 immunoreactivity was present in the neuritic component of senile plaques as well as in neurofibrillary tangles. Localization of PS1 immunoreactivity in familial and sporadic Alzheimer's disease suggests that genetically heterogeneous forms of the disease share a common pathophysiology involving PS1 protein.
Multiple sclerosis: Re‐expression of a developmental gene in chronic lesions correlates with remyelination
Authors: Capello Elisabetta , Voskuhl Rhonda R. , McFarland Henry F. , Raine Cedric S. 
Published: January 2005

AbstractCentral nervous system tissue from multiple sclerosis and non‐multiple sclerosis subjects was studied for the expression of exon 2 myelin basic protein gene products at the protein and message levels by immunocytochemistry and in situ hybridization, respectively. The exon 2‐encoded protein sequence is normally expressed during development (myelination) within the 21 · 5‐ and 20 · 2‐kd isoforms of myelin basic protein and is downregulated in the adult central nervous system where the 18 · 5‐ and 17 · 2‐kd isoforms predominate, the latter devoid of exon 2 owing to alternative splicing. Exon 2 myelin basic protein gene products were readily demonstrable in multiple sclerosis samples, the highest levels correlating with remyelination in chronic lesions while normal adult central nervous system and non‐multiple sclerosis material showed very low levels and fetal human central nervous system tissue (a positive control) showed high levels. We conclude that recapitulation of ontogenetic events during myelin repair accounts for the increased expression of the exon 2‐encoded protein sequence in the adult central nervous system during multiple sclerosis, an event that might underly the previously observed T‐cell activation to this protein sequence during relapses.
Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease
Authors: Augood S. J. , Faull R. L. M. , Emson P. C. 
Published: January 2005

AbstractThe cellular expression of dopamine D1 and D2 receptor mRNAs was investigated in the postmortem human caudate nucleus of control cases and genetically and pathologically confirmed cases of Huntington's disease (HD) by using quantitative in situ hybridization. The HD cases were categorized (0–4) by severity of striatal neuropathology according to the Vonsattel scale. For the HD grade 0 case, a pronounced reduction in the number of D1 and D2 mRNA‐positive cells was observed compared with controls; however, the abundance of both receptor mRNAs per remaining cell was within the control range. For D2 receptor mRNA, the number of detectable D2−positive medium‐sized cells decreased with increasing pathology; this decrease was accompanied by a gradual reduction in the intensity of D2 signal per cell. By contrast, for D1 receptor mRNA, despite a decrease in the number of D1 mRNA‐positive cells detected, the average cellular expression of D1 mRNA was markedly reduced in the HD grade 1 case and then increased (relative to the grade 1 case) with increasing pathology, presumably reflecting the relative survival of D1−expressing striatal interneurons. The implications of these findings for providing further information on the neurodegenerative process in HD are discussed.
Apolipoprotein E genotypes in a neuropathological series from the consortium to establish a registry for Alzheimer's disease
Authors: Welsh‐Bohmer Kathleen A. , Gearing Marla , Saunders Ann M. , Roses Allen D. , Mirra Suzanne 
Published: January 2005

AbstractWe evaluated the sensitivity, specificity, and predictive value of the apolipoprotein E (ApoE) ε4 allele for the neuropathological diagnosis of Alzheimer disease (AD) in a clinical series of well‐characterized AD patients and controls followed longitudinally in the multicenter study of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). In the 162 patients for whom autopsy and ApoE genotype data were available, the clinical diagnosis of AD was verified as the primary cause of dementia in 139 cases (139 of 162, or 86%). The sensitivity and specificity of the ε4 allele for AD were both 83%. The positive predictive value of the ε4 allele was very high at 97% (115 of 119); whereas, the negative predictive value was 44% (19 of 43), providing no useful information for diagnosis of AD when the ε4 allele is not present. Of the cases where AD was not considered the primary or sole cause of dementia (n = 23), 6 cases exhibited concomitant neuropathological findings of definite or probable AD and 2 of these 6 cases had at least one ε4 allele. These multicenter data extend previous obsevations reported from smaller case series of single laboratories and demonstrate that once the clinical diagnosis of AD is established, the presence of an ε4 allele reliably predicts the ultimate CERAD neuropathological diagnosis of AD. The findings also suggest that ApoE genotype information is useful clinically in bolstering diagnostic confidence when an ε4 allele is present and in identifying a group of patients for whom additional diagnostic evaluations may be warranted when the 4 allele is absent.
Apolipoprotein E ε2 does not increase risk of early‐onset sporadic Alzheimer's disease
Authors: Scott W. K. , Saunders A. M. , Gaskell P. C. , Locke P. A. , Growdon J. H. , Farrer L. A. , Auerbach S. A. , Roses A. D. , Haines J. L. , Pericak‐Vance M. A. 
Published: January 2005

AbstractWe examined the association of apolipoprotien E (ApoE) genotype and the risk of early‐onset Alzheimer's disease (AD) in 209 white early‐onset sporadic cases (43% male) and 303 white controls (48% male) of similar age distribution. The risk of AD was significantly increased, relative to the 3/3 genotype, in people with the 4/4, 3/4, and 2/4 genotypes, controlling for age at time of examination and sex. The 2/3 genotype reduced slightly the risk of AD, although the effect was not statistically significant. We conclude, contrary to some previous reprots, that the ApoE ε2 allele does not increase the risk of early‐onset sporadic AD.
Melatonin: A clinical perspective
Authors: Penev Palmen D. , Zee Phyllis C. 
Published: January 2005

AbstractOver the last several decades the pineal gland has emerged as an active neuroendocrine transducer of important environmental information. However, the current understanding of the function of its major hormone, melatonin, in humans remains ill defined and based exclusively on corelative observations. In a similar manner, the multitude of phenomenological descriptions of the effects of exogenous melatonin is contrasted by the limited understanding of the underlying mechanisms and the lack of firmly established clinical applications for the hormone. Future randomized, double‐blind, placebo‐controlled clinical studies wil be necessary to determine the precise indications, treatment regimens, and safety of melatonin in clinical practice. The recent rapid progress in the area of melatonin research should lead to a better understanding of its role in human health and disease.
Functional magnetic resonance imaging of single motor events reveals human presupplementary motor area
Authors: Humberstone Miles , Sawle Guy V. , Clare Stuart , Hykin Jonathan , Coxon Ronald , Bowtell Richard , Macdonald Ian A. , Morris Peter G. 
Published: January 2005

AbstractConventional functional imaging paradigms use periods of repetitive task performance to generate sustained functional signal changes. We have developed a technique of imaging the small, transient signal changes that occur after single cognitive events. The technique uses echo‐planar imaging at 3 T to generate functional images of the whole brain with a temporal resolution of 3 seconds. It uses a signal averaging technique to create time sweeps of functional activity. After a single cognitive event, widely distributed patterns of brain activation can be detected and their time course measured. This technique enables the individual cognitive tasks that constitute a paradigm to be analyzed separately and compared. We describe the application of this new technique to separate the cognitive elements in a simple “go/no‐go” motor paradigm. Comparison of activation patterns during “go” and “no‐go” responses reveals hierarchical subdivision of the medial premotor cortex into an anterior region (presupplementary motor area) involved in movement decision making and a posterior region (supplementary motor area proper) directly involved in motor execution.