bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and magnetic resonance imaging findings in batten disease: Analysis of the major mutation (1.02‐kb deletion)
Authors: Järvelä Irma , Autti Taina , Lamminranta Sirkka , Åberg Laura , Raininko Raili , Santavuori Pirkko 
Published: January 2005

AbstractA total of 36 patients with Batten disease (juvenile‐onset neuronal ceroid lipofuscinosis), homozygous or heterozygous for the major mutation, a 1.02‐kb deletion, in the CLN3 gene, were studied to relate their genotype to their clinical phenotype. The onset of visual failure and epilepsy was highly concordant in both groups. Great inter and intrafamilial heterogeneity was demonstrated in the development of mental and physical handicap and in magnetic resonance imaging findings among both homozygous and heterozygous patients. The 1.02‐kb deletion in homozygous form was always associated with mental and physical handicap, whereas the heterozygous phenotype could be extremely benign without affecting the intellectual level of the patient. Our data suggest that genetic background, modifying genes, and environmental factors all influence the final phenotype of Batten disease.
Presurgical multimodality neuroimaging in electroencephalographic lateralized temporal lobe epilepsy
Authors: Knowlton Robert C. , Laxer Kenneth D. , Ende Gabriele , Hawkins Randall A. , Wong Stephen T. C. , Matson Gerald B. , Rowley Howard A. , Fein George , Weiner Michael W. 
Published: January 2005

AbstractThe purpose of this study was to compare 2hyphen;[18F]fluoro‐2‐deoxy−D−glucose positron emission tomography (FDG‐PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H‐MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)‐defined unilateral temporal lobe epilepsy (TLE). Twenty‐five patients were prospectively studied, along with age‐matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG‐PET, HV, and 1H‐MRSI was possible in 23 patients. FDG‐PET lateralized 87% of patients, HV 65%, N‐acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61% and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG‐PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H‐MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure‐free outcome. FDG‐PET remains the most sensitive imaging method to correlate with EEG‐lateralized TLE. Both FDG‐PET and 1H‐MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure‐free outcome. Bilaterally abnorma; MRI and 1H‐MRSI measures do not preclude good surgical outcome.
Human immunodeficiency virus type 1 and its coat protein gp 120 induce apoptosis and activate JNK and ERK mitogen‐activated protein kinases in human neurons
Authors: Lannuzel Annie , Tardieu Marc , Hery Christiane , Barnier Jean Vianney , Vincent Jean Didier , Guibert Bernard , Van Tan Huynh , Gray Francoise 
Published: January 2005

AbstractDetection of apoptotic neurons and microglial cells in the brains of human immunodeficiency virus type 1 (HIV‐1)‐infected patients has suggested that programmed cell death may be implicated in the physiolpathology of HIV‐1 encephalopathy. To analyze in vitro the intracellular signals induced by HIV‐1 in human neurons and the associated neuronal death, we tested cultured human central nervous system (CNS) cells for apoptosis induced by HIV‐1 and gp120 and for signaling pathways activated by gp120. HIV‐1 and gp120 induced apoptosis of neurons and microglial cells but not of astrocytes or transformed microglial cells. Gp120 activated c‐Jun N‐terminal kinase (JNK) and p42 extracellular regulated kinase (ERK) in primary CNS cells, with an early peak of activation at 2 to 5 minutes that was not present when pure microglial or astrocyte cultures were tested, followed by a late and sustained activation (10 and 60 minutes) in primary and enriched glial cell cultures as well as in transformed microglial cells. This demonstrates that gp120 could be an effector of HIV‐1‐induced apoptosis in the CNS and act directly on neuronal and glial cells.
Amyloid β‐protein deposition in the leptomeninges and cerebral cortex
Authors: Shinkai Yasuhisa , Morishima‐Kawashima Maho , Ihara Yasuo , Yoshimura Masahiro , Shimada Hiroyuki , Ito Yuji , Yanagisawa Katsuhiko 
Published: January 2005

AbstractTo further investigate the process of amyloid β‐protein (Aß) deposition, we determined, using sensitive enzyme immunoassays, the levels of Aβ40 and Aβ42 (Aβs) in the soluble and insoluble fractions of the leptomeninges (containing arachnoid mater and leptomeningeal vessels) and cerebral cortices from elderly control subjects showing various stages of Aβ deposition and from patients affected by Alzheimer's disease (AD). In both locations, insoluble Aβ levels were higher by ordersof magnitude than soluble Aβ levels. Soluble Aβ levels. Soluble Aβ levels in cortices were much lower than those in leptomeninges. In insoluble Aβ in the cortex, Aβ42 was by far the predominant species, and Aβ42 in AD cortices was characterized by the highest degree of modifications in the amino terminus. In contrast, this Aβ42 predominance was not observed in insoluble Aβ in the leptomenings, which were found to be able to accumulate Aβs to an extent similar to that in the cortex, on a weight basis. The levels of insoluble Aβ in the leptomeninges or cortex generally correlated with the degree of cerebral amyloid angiopathy or the abundance of senile plaque, respectively. However, the presence of plaque‐free cortical samples showing significant levels of insoluble Aβ42 suggests that biochemically detectable Aβ accumulation precedes immunocytochemically detectable Aβ deposition in the cortex.
A triethnic comparison of intracerebral hemorrhage mortality in Texas
Authors: Morgenstern Lewis B. , Spears William D. 
Published: January 2005

AbstractIntracerebral hemorrhage (ICH) is a significant cause of stroke death. Little is known about the relative risk of Hispanic Americans (HAs), African Americans (AAs), and non‐Hispanic whites (NHWs) for ICH mortality. Based on the high prevalence of hypertension in AAs and the low prevalence of hypertension in HAs, we expected AAs to have the highest ICH mortality rates and HAs the lowest. Race/ethnic age‐specific ICH mortality rates were calculated from Texas vital statistics for the years 1980 through 1995. Rate ratios (RRs) are reported with NHWs as the referent group. There were 15,042 deaths due to ICH in Texas during this time. In the 45‐ to 59‐year age group, AAs had an RR of 4. The RR for HAs was 1.9. In the 60hyphen; to 74‐year age range, AAs had an RR of 1.7 and HAs had an RR of 1.3. In the 75+ age group, the rates were similar among all three race/ethnic groups. We conclude that there is a significant interaction of age and race/ethnicity for ICH. At younger ages, AAs and HAs have the highest ICH mortality rates. Access to care and socioeconomic status may play a role in the unexpectedly high ICH mortality rates in HAs.
Detection of 14‐3‐3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt‐Jakob disease
Authors: Zerr Inga , Bodemer Monika , Gefeller Olaf , Otto Markus , Poser Sigrid , Wiltfang Jens , Windl Otto , Kretzschmar Hans A. , Weber Thomas 
Published: January 2005

AbstractThe analysis of 14‐3‐3 protein in cerebrospinal fluid (CSF) was shown to be highly sensitive and specific for the diagnosis of Creutzfeldt‐Jakob disease (CJD). However, the predictive value of this test in the clinical diagnosis of, and its relation to, sporadic, genetic, and iatrogenic CJD cases have yet to be established. CSF samples of suspect CJD cases seen in the prospective German surveillance study were tested for the presence of 14‐3‐3 protein by using a modified western blot (WB) technique. WB detected 14‐3‐3 protein in 95.4% of definite and 92.8% of probable cases. In two patients classified initially as not having CJD the test was positive, and both were later proved to have definite CJD. The positive predictive value is 94.7% and the negative predictive value is 92.4%. False‐positive results in a single CSF analysis were seen in patients with herpes simplex encephalitis, hypoxic brain damage, atypical encephalitis, intracerebral metastases of a bronchial carcinoma, metabolic encephalopathy, and progressive dementia of unknown cause. WB analysis for 14‐3‐3 protein was positive in only 5 of 10 cases of familial forms of spongiform encephalopathies. CSF analysis for 14‐3‐3 protein should thus be performed in any case suspect for CJD.
Physiological characterization of taxol‐induced large‐fiber sensory neuropathy in the rat
Authors: Cliffer Kenneth D. , Siuciak Judith A. , Carson Susan R. , Radley Heather E. , Park John S. , Lewis Dacie R. , Zlotchenko Elizabeth , Nguyen Trang , Garcia Karen , Tonra James R. , Stambler Nancy , Cedarbaum Jesse M. , Bodine Sue C. , Lindsay Ronald M. , Distefano Peter S. 
Published: January 2005

AbstractThe cancer chemotherapeutic agent Taxol (paclitaxel) causes a dose‐related peripheral neuropathy in humans. We produced a dose‐dependent large‐fiber sensory neuropathy, without detrimental effects on general health, in mature rats by using two intravenous injections 3 days apart. Tests of other dosing schedules demonstrated the dependence of the severity of the neuropathy and of animal health on both the dose and the frequency of dosing. Pathologically, severe axonal degeneration and hypomyelination were observed in sections of dorsal roots, whereas ventral roots remained intact. Electrophysiologically, H‐wave amplitudes in the hindlimb and amplitudes of predominantly sensory compound nerve action potentials in the tail were reduced. These effects persisted for at least 4 months after treatment. Motor amplitudes were not affected, but both motor and sensory conduction velocities decreased. The ability of rats to remain balanced on a narrow beam was impaired, indicating proprioceptive deficits. Muscle strength, measured by hindlimb and forelimb grip strength, and heat nociception, measured by tail‐flick and hindlimb withdrawal tests, were not affected by Taxol. This model of Taxol‐induced neuropathy in mature rats, with minimal effects on general health, parallels closely the clinical syndrome observed after Taxol treatment in humans.
Cytochrome c Oxidase subunit I microdeletion in a patient with motor neuron disease
Authors: Comi Giacomo P. , Bordoni Andreina , Salani Sabrina , Franceschina Liliana , Sciacco Monica , Prelle Alessandro , Fortunato Francesco , Zeviani Massimo , Napoli Laura , Bresolin Nereo , Moggio Maurizio , Ausenda Carlo D. , Taanman Jan‐Willem , Scarlato Guglielmo 
Published: January 2005

AbstractAn out‐of‐frame mutation of the mitochondrial DNA‐encoded subunit I of cytochrome c oxidase (COX) was discovered during investigation of a severe isolated muscle COX deficiency in a patient with motor neuron‐like degeneration. The mutation is a heteroplasmic 5‐bp microdeletion located in the 5′ end of the COI gene, leading to premature termination of the corresponding translation product. Western blot analysis, immunohistochemistry, and single‐fiber polymerase chain reaction demonstrated a tight correlation between COX defect, COX I expression, and percentage of mutation. COX subunits II, III, and IV were decreased as well, suggesting a defective assembly of COX holoenzyme. The mutation was associated with a clinical phenotype unusual for a mitochondrial disorder, that is, an isolated motor neuron disease(MND) with some atypical findings, including early onset, preferential involvement of the upper motor neuron, and increased cerebrospinal fluid protein content. MND may arise from impaired scavenging and overproduction of free oxygen radicals, a by‐product of oxidative phosphorylation (OXPHOS). Our observation suggests that OXPHOS impairment could play a role in the pathogenesis of some MND cases.
Association between the gene encoding the E2 subunit of the α‐ketoglutarate dehydrogenase complex and Parkinson's disease
Authors: Kobayashi Tomonori , Matsumine Hiroto , Matuda Sadayuki , Mizuno Yoshikuni 
Published: January 2005

AbstractDihydrolipoamide succinyltransferase (E2, EC 2.3.1.61, chromosome 14q24.2–3) is a specific subunit of human α‐ketoglutarate dehydrogenase complex (KGDHC). A biallelic intragenic polymorphism was identified in E2 gene of KGDHC. It was a single nucleotide substitution between G (in allele 1) and A (in allele 2) at the position that does not change amino acid code. Using this intragenic polymorphism as a marker, we investigated the association between this gene and Parkinson's disease. Frequencies of the genotypes that carry allele 2 were significantly higher in the Parkinson's disease group than in the control group. The results indicated that a genetic variant of the E2 gene itself or in close proximity to the gene constitutes one of the genetic risk factors for Parkinson's disease.
Amyloid angiopathy in a volga german family with Alzheimer's disease and a presenilin‐2 mutation (N141I)
Authors: Nochlin David , Bird Thomas D. , Nemens Ellen J. , Ball Melvyn J. , Sumi S. Mark 
Published: January 2005

AbstractWe report the neuropathological features in 6 members of a Volga German family with autosomal dominant Alzheimer's disease linked to chromosome 1 who had a presenilin‐2 mutation (N141I). The most significant feature in this family was the presence of severe or moderately severe amyloid angiopathy in five family members with clinical dementia. The index case with the presenilin‐2 mutation had late‐onset dementia at age 73 years, died of an acute intracerebral hemorrhage, and pathologically showed severe amyloid angiopathy but only rare neuritic senile plaques and neurofibrillary tangles. That she was apolipoprotein E ϵ2/3 heterozygous suggests that the ϵ2 allele may have exerted a selective protective effect resulting in late onset relatively mild Alzheimer's disease despite severe amyloid angiopathy. This family emphasizes the need for more investigation into the role of presenilin mutation in amyloid deposition, especially in the cerebral vasculature, and the role of these changes in clinical dementia.
Localization of the giant axonal neuropathy gene to chromosome 16q24
Authors: Flanigan Kevin M. , Crawford Thomas O. , Griffin John W. , Goebel Hans H. , Kohlschütter Alfried , Ranells Judith , Camfield Peter R. , Ptáček Louis J. 
Published: January 2005

AbstractGiant axonal neuropathy (GAN) is a degenerative disorder of the peripheral nerves that is inherited as an autosomal recessive trait, presenting in early childhood and progressing to death, usually by late adolescence. Diagnosis is made by peripheral nerve biopsy, in which a striking pathological finding is seen—fibers distorted by giant axonal swellings filled with densely packed bundles of neurofilaments (the primary intermediate filament in neurons), with segregation of other axoplasmic organelles. In addition to disorganized neurofilaments in nerve, disorganization of other members of the intermediate filament family of proteins is seen in other tissues; this implies that the underlying defect is one of generalized intermediate filament organization, with neurofilaments predominantly affected. We have pursued a genomewide search for regions of homozygosity of descent in 5 consanguineous families. A 5.3‐cM region of homozygosity, shared in all 5 families, was found on chromosome 16q24, and linkage was established to this locus with a LOD score of 4.18 at Θ = 0.00 at the most tightly linked marker, D16S3098. Determination of this locus is the first step toward characterizing the gene responsible for a fundamental property of intermediate filament organization and may shed light on other disorders (such as amyotrophic lateral sclerosis) in which neurofilament pathology is prominent.
Depletion of catecholaminergic neurons of the rostral ventrolateral medulla in multiple systems atrophy with autonomic failure
Authors: Benarroch Eduardo E. , Smithson Inge L. , Low Phillip A. , Parisi Joseph E. 
Published: January 2005

AbstractThe ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]‐positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4°C for 24 hours and cut into 1‐cm blocks in the coronal plane from throughout the medulla. Serial 50‐μm sections were collected and one section every 300 μm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.
[11C]Raclopride‐PET studies of the Huntington's disease rate of progression: Relevance of the trinucleotide repeat length
Authors: Antonini Angelo , Leenders Klaus L. , Eidelberg David 
Published: January 2005

AbstractWe used [11C]raclopride and positron emission tomography (PET) to assess the relationship between striatal dopamine D2 receptor binding, trinucleotide repeat number (CAG), and subject age in 10 asymptomatic and 8 symptomatic carriers of the Huntington's disease (HD) mutation. In both preclinical and symptomatic gene carriers, we found significant correlations between CAG repeat length and the ratio of percent loss in striatal D2 receptor binding divided by age. In accord with neuropathological studies, we obtained an intercept at 35.5 CAG repeats in the symptomatic HD patients. Nontheless, we noted that the slopes of the correlation lines differed significantly for the presymptomatic and symptomatic cohorts. These PET results support the notion that the HD disease process is a function of trinucleotide length and age, and that the development of clinical signs and symptoms is associated with CAG repeat lengths greater than 35.5. However, our analysis also suggests that striatal degeneration may proceed in a nonlinear fashion. These findings have implications for the design of neuroprotective strategies for the treatment of HD.
Facioscapulohumeral dystrophy: A distinct regional myopathy with a novel molecular pathogenesis
Authors: Tawil Rabi , Figlewicz Denise A. , Griggs Robert C. , Weiffenbach Barbara ,   The FSH Consortium
Published: January 2005

AbstractFacioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited diseases of muscle. Until recently, FSHD had received little attention because of its relatively benign course and the perception that it represented a syndrome rather than a distinct myopathy. Research interest into this disease was reignited with the demonstration of linkage of FSHD to chromosome 4q35 in 1990. Clinical and molecular genetic research in FSHD has since helped define it as a distinct clinical entity, outlined its natural history, and defined the primary molecular defect associated with the condition. FSHD is now known to be associated with large deletions of variable size on chromosome 4q35. These deletions, however, do not appear to disrupt a transcribed gene but are thought to interfere with the expression of a gene or genes located proximal to the deletions. These observations complicate the search for the FSHD gene but also imply the presence of a potentially novel molecular pathognesis.
Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease
Authors: Jack Clifford R. , Petersen Ronald C. , Xu Yue Cheng , O'Brien Peter C. , Waring Stephen C. , Tangalos Eric G. , Smith Glenn E. , Ivnik Robert J. , Thibodeau Stephen N. , Kokmen Emre 
Published: January 2005

AbstractA variety of anatomic and functional neuroimaging findings are associated with Alzheimer's disease (AD). One of the strongest imaging associations identified is between AD and hippocampal atrophy. The ∈4 allele of the apolipoprotein E (ApoE) gene increases the risk of developing AD and lowers the mean age of onset of the disease. The purpose of this study was to assess the association between hippocampal volume and ApoE polymorphisms in elderly control subjects and in patients with probable AD. We performed magnetic resonance imaging–based volume measurements of the hippocampus in 125 cognitively normal elderly controls and 62 patients with probable AD. ApoE genotyping was performed by using standard methods. Hippocampal volumes were significantly smaller in AD cases than in control subjects. Hippocampal volumes did not differ significantly within either clinical group on the basis of ApoE genotype. Both the ∈4 allele of ApoE and hippocampal atrophy were significantly but independently associated with AD.
Mortality in DATATOP: A Multicenter trial in early Parkinson's disease
Authors: Shoulson  ,   Parkinson Study Group
Published: January 2005

AbstractDeprenyl (selegiline) delays the need for levodopa therapy in patients with early Parkinson's disease, but the value of long‐term treatment with this type B monoamine oxidase inhibitor remains unsettled. We examined mortality among the 800 patients with early Parkinson's disease who were not requiring levodopa and who were randomly assigned in the DATATOP trial to receive deprenyl, tocopherol, combined treatments, or placebo. Ascertainment of the vital status of subjects in this double‐blinded trial was performed prospectively after the initial randomization, during open‐label de‐prenyl, and after a second independent randomization to continue active deprenyl or swithch to matching placebo. The study was conducted at 28 academic medical centers in the United States and Canada. After an average of 8.2 years of observation, the overall death rate of our subjects was 17.1% (137 of 800) or 2.1% per year. The mortality rate was unaffected by deprenyl, tocopherol, or combined treatment assignments and was about that expected for an age‐ and gender‐matched US population without Parkinson's disease. Neither deprenyl, tocopherol, nor their combined treatments affected the duration of life in our early Parkinson's disease patients. The deprenyl‐related delay in disability that we reported previously was not associated with a deprenyl‐related reduction in mortality.