bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early copper therapy in classic Menkes disease patients with a novel splicing mutation
Authors: Kaler Stephen G. , Buist Neil R. M. , Holmes Courtney S. , Goldstein David S. , Miller Richard C. , Gahl William A. 
Published: January 2005

AbstractTo correlate genotype with response to early copper histidine therapy in Menkes disease, an X‐linked disorder of copper transport, we performed mutational analysis in 2 related males who began treatment at the age of 10 days and prenatally at 32 weeks' gestation, respectively. A G to T transversion at the —1 exonic position of a splice donor site was identified, predicting a glutamine to histidine substitution at codon 724 of the Menkes copper‐transporting ATPase gene. The Q724H mutation disrupts proper splicing and generates five mutant transcripts that skip from one to four exons. None of these transcripts is predicted to encode a functional copper transport protein. Copper histidine treatment normalized circulating copper and ceruloplasmin levels but did not improve the baseline deficiency of dopamine‐β‐hydroxylase, a copper‐dependent enzyme. At the age of 36 months, the first patient was living and had neurodevelopmental abilities ranging from 10 to 15 months. The second patient also showed delayed neurodevelopment and died of pulmonary complications at the age of 5 1/2 months. We conclude that early copper histidine therapy does not normalize neurological outcome in patients with the Q724H splicing mutation, and suggest that preservation of some residual Menkes ATPase activity may be a general prerequisite for significant clinical efficacy from such treatment.
Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions
Authors: Gilman Sid , Sima Anders A. F. , Junck Larry , Kluin Karen J. , Koeppe Robert A. , Lohman Mary E. , Little Roderick 
Published: January 2005

AbstractSpinocerebellar ataxia type 1 (SCA1) is a dominantly inherited progressive neurological disorder characterized by neuronal degeneration and reactive gliosis in the cerebellum, brainstem, spinocerebellar tracts, and dorsal columns. Multiple system atrophy is a sporadic progressive neurological disorder with degeneration and gliosis in the basal ganglia, cerebellum, brainstem, and spinal autonomic nuclei, and with argyrophilic glial cytoplasmic inclusions. We describe 4 members of a family with the SCAl mutation and a dominantly inherited progressive ataxia in which autopsy examination of 1 member showed neuropathological changes typical of multiple system atrophy, including glial cytoplasmic inclusions. In this patient, magnetic resonance imaging revealed marked brainstem and cerebellar volume loss and mild supratentorial generalized volume loss. Positron emission tomography with [18F]fluorodeoxyglucose revealed widespread hypometabolism in a pattern found in sporadic multiple system atrophy and not in dominantly inherited olivopontocerebellar atrophy. Positron emission tomography with [llC]flumazenil revealed normal benzodiazepine receptor distribution volumes, similar to those seen in sporadic multiple system atrophy. Two other family members still living had similar changes in the imaging studies. The findings in this family suggest that the SCAl gene mutation can result in a disorder similar to multiple system atrophy, both clinically and neuropathologically.
Wolfram syndrome: Hereditary diabetes mellitus with brainstem and optic atrophy
Authors: Scolding Neil J. , Kellar‐Wood Helen F. , Shaw C. , Shneerson John M. , Antount Nagui 
Published: January 2005

AbstractWolfram syndrome was originally described as a combination of familial juvenile‐onset diabetes mellitus and optic atrophy. Other neurological features subsequently emerged, and “DIDMOAD” (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) became a commonly accepted acronym. Here, we describe 4 further cases from 2 families, in whom there occurred previously unrecognized neurological features, central apnea and neurogenic upper airway collapse, together precipitating primary respiratory failure (fatal in 1 case), startle myoclonus (in 2 unrelated cases), axial rigidity, and Parinaud's syndrome. Magnetic resonance images revealed striking brainstem atrophy affecting, in particular, the pons and midbrain. The mitochondrial DNA from 3 cases (and relatives) showed no evidence of any of the previously reported abnormalities. These neurological and neuroradiological features, in conjunction with (1) analyses showing the neurodegenerative origin of optic atrophy, deafness, diabetes insipidus, and incontinence, (2) other previously reported neurological complications (including anosmia, ataxia, epilepsy, and neuropsychiatric and cognitive abnormalities), and (3) the very small number of published postmortem studies, indicate that Wolfram syndrome should be reemphasized as a unique hereditary neurodegenerative disorder with prominent optic atrophy and diabetes mellitus.
Aβ‐peptide length aid apolipoprotein E genotype in Alzheimer's disease
Authors: Gearing Marla , Mori Hiroshi , Mirra Suzanne S. 
Published: January 2005

AbstractApolipoprotein ∈ (ApoE)ε4 allele, a risk factor for the development of Alzheimer's disease (AD), is associated with increased amyloid deposition. We examined cerebral cortex in 68 AD cases using antibodies to βbeta;‐amyloid (Aβbeta;) peptides of different length (Aβbeta;1−40 and Aβbeta;l−42) and found that the increased plaque frequency observed with ε4 genotypes may be largely attributed to an increase in Aβbeta;1−40‐positive plaques. Indeed, both the number of Aβbeta;1−40‐positive plaques, as well as the ratio of Aβbeta;I−40/ Aβbeta;1−42‐positive plaques, increased with ε4 dosage. In contrast, the frequency of Aβbeta;1−42‐immunoreactive plaques was similar for ε3/ε3,ε3/ε4 and ε4/ε4 genotypes. ApoE may influence Aβbeta; length by facilitating Aβbeta; 1−40 deposition onto Aβbeta;1−42‐seeded plaques or by modulating the activity of a putative carboxypeptidase that forms Aβbeta;1−40 from Aβbeta;1−42 in situ.
Impact of aerobic training on fitness and quality of life in multiple sclerosis
Authors: Petajan Jack H. , Gappmaier Eduard , White Andrea T. , Spencer Mark K. , Mino Lizbeth , Hicks Richard W. 
Published: January 2005

AbstractFifty‐four multiple sclerosis (MS) patients were randomly assigned to exercise (EX) or nonexercise (NEX) groups. Before and after 15 weeks of aerobic training, aspects of fitness including maximal aerobic capacity (Vo2max), isometric strength, body composition, and blood lipids were measured. Daily activities, mood, fatigue, and disease status were measured by the Profile of Mood States (POMS), Sickness Impact Profile (SIP), Fatigue Severity Scale (FSS), and neurological examination. Training consisted of 3 × 40‐minute sessions per week of combined arm and leg ergometry. Expanded Disability Status Scale (EDSS) scores were unchanged, except for improved bowel and bladder function in the EX group. Compared with baseline, the EX group demonstrated significant increases in Vo2max, upper and lower extremity strength, and significant decreases in skinfolds, triglyceride, and very‐low‐density lipoprotein (VLDL). For the EX group, POMS depression and anger scores were significantly reduced at weeks 5 and 10, and fatigue was reduced at week 10. The EX group improved significantly on all components of the physical dimension of the SIP and showed significant improvements for social interaction, emotional behavior, home management, total SIP score, and recreation and past times. No changes were observed for EX or NEX groups on the FSS. Exercise training resulted in improved fitness and had a positive impact on factors related to quality of life.
Anti‐GD1a ganglioside antibodies in peripheral motor syndromes
Authors: Carpo Marinella , Nobile‐Orazio Eduardo , Meucci Nicoletta , Gamba Massimo , Barbieri Sergio , Allaria Silvia , Scarlato Guglielmo 
Published: January 2005

AbstractHigh titers of anti‐GD 1a antibodies have been found in patients with Guillain‐Barŕe syndrome or motor neuropathy. To determine the possible diagnostic relevance of these antibodies, we measured serum anti‐GD 1a IgG and IgM antibodies by enzyme‐linked immunosorbent assay in 195 patients with different motor syndromes and in 335 control subjects. Moderately high antibody titers (I/ 1,280‐1/5,120) were occasionally found in patients with chronic inflammatory demyelinating polyneuropathy (5%), multifocal motor neuropathy (18%), lower motor neuron disease (3.8%), or amyotrophic lateral sclerosis (1.8%) and in immunological control subjects (1.2%), while titers of 1/20,480 or higher were only found in 2 patients with Guillain‐Barri! syndrome (IgG in both) and 2 with motor neuropathy and IgMλ monoclonal gam‐mopathy improving with immunotherapy. In both motor neuropathy patients and the Guillain‐Barŕe syndrome patient who were retested during recovery, anti‐GD 1a titers decreased concomitantly with clinical improvement. High anti‐GD 1a antibody titers may be found in several motor syndromes but only markedly increased anti‐GD 1a titers are strictly associated with potentially treatable dysimmune neuropathies.
Human T‐lymphotropic virus type I‐associated myelopathy and tax gene expression in CD4+ T lymphocytes
Authors: Moritoyo Takashi , Reinhart Todd A. , Haase Ashley T. , Moritoyo Hiroyoko , Izumo Shuji , Osame Mitsuhiro , Sato Eiichi 
Published: January 2005

AbstractInfection by human T‐lymphotropic virus type I (HTLV‐I) is associated with adult T‐cell leukemia and a slowly progressive disease of the central nervous system (CNS), HTLV‐I‐associated myelopathy/tropical spastic paraparesis, characterized pathologically by inflammation and white matter degeneration in the spinal cord. One of the explanations for the tissue destruction is that HTLV‐I infects cells in the CNS, or HTLV‐I‐infected CD4+ T lymphocytes enter the CNS, and this drives local expansion of virus‐specific CD8+ cytotoxic T lymphocytes, which along with cytokines cause the pathological changes. Because both in the circulation and in the cerebrospinal fluid, CD8+ cytotoxic T lymphocytes are primarily reactive to the product of the HTLV‐I tax gene, we sought evidence of expression of this gene within cells in the inflammatory lesions. After using double‐label in situ hybridization techniques, we now report definitive localization of HTLV‐I tax gene expression in CD4+ T lymphocytes in areas of inflammation and white matter destruction. These findings lend support to a hypothetical scheme of neuropathogenesis in which HTLV‐I tax gene expression provokes and sustains an immunopathological process that progressively destroys myelin and axons in the spinal cord.
Effect of lazabemide on the progression of disability in early Parkinson's disease
Authors: Kieburtz  
Published: January 2005

AbstractLazabemide (Ro 19‐6327) is a relatively short‐acting, reversible, and selective type B monoamine oxidase inhibitor that is not metabolized to amphetamines or other active compounds. We previously found lazabemide to be safe and well tolerated at dosages of up to 400 mg/day during a 6‐week study of 201 patients with early untereated Parkinson's disease (PD). We now assess whether or not lazabemide influences the progression of disability in untreated PD. Patients (N = 321) were assigned by randomization to one of five treatment groups (placebo, 25 mg, 50 mg, 100 mg, or 200 mg/day) and followed systematically for up to 1 year. The risk of reaching the primary end point (the onset of disability sufficient to require levodopa therapy) was reduced by 51% for the patients who received lazabemide compared with placebo‐treated subjects. This effect was consistent among all dosages. The frequency of adverse experiences did not placebo‐treated subjects. This effect was consistent among all dosages. The frequency of adverse experiences did not differ among the treatment groups. At dosages ranging from 25 to 200 mg/day, lazabemide was well tolerated and delayed the need for levodopa in early, otherwise untreated PD. The magnitude and pattern of benefits were similar to those observed after 1 year of deprenyl (selegiline) treatment in the DATATOP clinical trial.
Motor neuron disease: A paraneoplastic process associated with anti‐Hu antibody and small‐cell lung carcinoma
Authors: Verma Ashok , Berger Joseph R. , Snodgrass Susan , Petito Carol 
Published: January 2005

AbstractAlthough isolated lower motor neuron disease has been reported as a paraneoplastic complication, it has not been previously described in association with anti‐Hu antibody. We report a 51‐year‐old man in whom weakness heralded the presence of a small‐cell cancer of the lung. His neurological disorder was characterized by an unremitting progression of limb, neck, and chest wall weakness and wasting that commenced and remained predominant in the upper limbs. Electrophysiological studies demonstrated widespread denervation and examination of a muscle biopsy specimen showed evidence of acute and chronic denervation. High titers of anti‐Hu antibody were detected in the serum and cerebrospinal fluid. Neither objective measures of strength nor titers of anti‐Hu antibody responded to corticosteroids, cyclophosphamide, intravenous immunoglobulins, or plasmapheresis. Death from the complications of motor neuron disease ensued 23 months after the onset of weakness. Autopsy revealed tumor in the lung and on pleural and peritoneal surfaces. There was a loss of anterior horn cells in the spinal cord. Despite the absence of symptomatic cerebellar disease, a decrease in the number of Purkinje cells was also detected.
Neurodegenerative disorders with extensive tau pathology: A comparative study and review
Authors: Feany Mel B. , Dickson Dennis W. 
Published: January 2005

AbstractMany neurodegenerative disorders with onset in mid to late adult life present diagnostic challenges to clinicians and pathologists alike. A distinguishing neuropathological feature has traditionally been the presence or absence of neurofibrillary tangles. Recent biochemical and molecular biological studies have identified the microtubule‐binding protein tau as the predominant component of these and related inclusions, and have provided powerful new reagents for the study of neurodegenerative diseases. Several diseases previously considered distinct pathophysiological entities contain similar tau‐immunoreactive lesions, but qualitative and regional anatomical differences in vulnerability can differentiate the disorders. Comparison of tau‐immunoreactive lesions in three relatively uncommon neurodegenerative diseases—progressive supranuclear palsy, Pick's disease, and corticobasal degeneration—illustrates the types of analyses that demonstrate unexpeceted pathological similarities, but also fundamental differences between these disorders. These results have important implications for the differential diagnosis of disorders containing tau‐immunoreactive lesions, including Alzheimer's disease.
Sequence of mitochondrial DNA in patients with multiple sclerosis
Authors: Chalmers R. M. , Harding A. E. , Robertson N. , Compston D. A. S. 
Published: January 2005

AbstractThe excess female transmission of multiple sclerosis (MS) and the observation of an MS‐like illness in patients with Leber's hereditary optic neuropathy who carry a mitochondrial DNA mutation may indicate that mitochondrial genes contribute to the genetic susceptibility to MS. We sequenced the protein‐ and RNA‐coding sequences of 9 patients with MS who had a family history of MS consistent with maternal transmission. Four base‐pair (bp) changes of particular interest were identified. Those at bp 4216 and 4917 may play a role in the etiology of Leber's hereditary optic neuropathy. Two others, at bp 11447 and 14766, were found in all MS patients sequenced. Restriction enzyme analysis used to screen 175 unrelated MS patients and 233 healthy control subjects showed that each of these changes was present in MS patients at a similar frequency to control subjects. The 4216 and 4917 changes were at a higher frequency in north European control subjects than previously documented. We conclude that variation in mitochondrial DNA is unlikely to contribute to susceptibility to MS. The etiology of the overlap between Leber's hereditary optic neuropathy and MS remains unexplained.
Altered mental status in thrombotic thrombocytopenic purpura is secondary to nonconvulsive status epilepticus
Authors: Garrett William T. , Bleck Thomas P. , Chang Cherylee W. J. 
Published: January 2005

AbstractThrombotic thrombocytopenic purpura (TTP) is a syndrome with numerous neurological manifestations including altered mental status and seizures. At least 10% of the patients with TTP seen at our institution had non‐convulsive status epilepticus as a cause of or associated with their altered mental status. We propose that altered mental status secondary to nonconvulsive status epilepticus requiring electroencephalographic diagnosis and antiepileptic medication occurs in a substantial proportion of patients with TTP.
Lambert‐eaton myasthenic syndrome immunoglobulins react with multiple types of calcium channels in small‐cell lung carcinoma
Authors: Meriney Stephen D. , Hulsizer Susan C. , Grinnell Alan D. , Lennon Vanda A. 
Published: January 2005

AbstractBarium currents through voltage‐gated calcium (Ca2+) channels were studied in the small‐cell lung carcinoma cell line NCI‐H345 using patch clamp techniques. Pharmacological dissection of whole‐cell barium currents revealed that 23% of the current was sensitive to nitrendipine, 35% to ω‐conotoxin GVIA, and between 10 and 39% to ω‐Aga‐IVA. This implies that these cells express L‐, N‐, and P‐type calcium channels. Only large cells expressed current that was sensitive to ω‐Aga‐IVA. The size dependency of this P‐type channel expression may reflect the cell cycle stage. Cell‐attached recordings revealed three unitary conductances: 5 to 6 pS, 10 to 12 pS, and 20 to 23 pS. The largest conductance channel (20‐23 pS) was sensitive to bay K 8644 and is presumed to represent L‐type calcium channels. The frequency of observing the medium conductance channel (10‐12 pS) was reduced by exposure to ω‐conotoxin GVIA and may represent N‐type channels. Incubation of cells with Lambert‐Eaton myasthenic syndrome IgG for 24 to 48 hours removed up to 71% of the whole‐cell current. Incubation with control human IgG (normal or myasthenia gravis) had no effect. Lambert‐Eaton maysthenic syndrome IgG did not selectively target one “presynaptic” type of calcium channel, but rather appeared to target many of the calcium channel types that are expressed on small‐cell lung carcinoma cells.
Acute and chronic effects of hypoxia on the developing hippocampus
Authors: Owens James , Robbins Carol A. , Wenzel H. Jurgen , Schwartzkroin Philip A. 
Published: January 2005

AbstractPerinatal hypoxia i associated with both seizures arising acutely and the subsequent development of temporal lobe epilepsy (as determined retrospectively). We terefore attempted to identify acute and chronic morphological and/or electrophysiological hippocampal pathologies assiciated with experimentally induced hypoxia in immature rats. Pups were exposed to 15 minutes of hypoxia on 3 successive days (starting on postnatal dya 8; P8), or to 60 minutes of hypoxia on P10 with either one or multiple hupoxia‐induced seizures. For animals experiencing multiple seizures, flurothyl seizure threshold was significantly lower than that of controls at 60 to 80 days, but not at 10 days, after hypoxia. Acutely, there was a treatment‐related increase in the number and the density of pyknotic dentate and hilar neurons, in particular in animals experiencing multiple seizures. However, 60 to 80 days after the multiple‐sezure protocol, the number of dentate and hilar neurons did not differ between expermental and control animals at any time point. These results indicate that early postnatal hupoxia and hypoxia‐induced seizure episodes decrease seizure threshold in the adult but produce minimal acute or chronic morphological or functional chages in the hippocampus.
Sequestration of RNA in Alzheimer's disease neurofibrillary tangles and senile plaques
Authors: Ginsberg Stephen D. , Crino Peter B. , Lee Virginia M.‐Y. , Eberwine James H. , Trojanowski John Q. 
Published: January 2005

AbstractThe polypeptide composition of neurofibrillary tangles (NFTs) and senile plaques (SPs) has been characterized extensively within the Alzheimer's disease (AD) brain. Because few data exist on the nonproteinaceous components of these lesions, we sought to determine if NFTs, neuropil threads (NTs), and SPs contain RNA species. To acoomplish this, acridine orange (AO) histofluorescence was employed, alone or in combination with thioflavine S (TS) staining and immunohistochemistry to identify RNAs in paraffin‐embedded tissue sections of hippocampus and entorhinal cortex. Postmortem brain samples came from 32 subjets including AD and elderly Down's syndrome (DS) patints, age‐matched normal controls, and non‐AD diseased controls. AO stained the cytoplasm of normal hippocampal and entorhinal neurons in all of the cases, while NFTs, NTs, and SPs were AO‐positive in the same regions of AD and DS brains. Cytoplasmic AO histofluorescence was abolished with RNase, but not DNase or proteinase K, indicating the relative specificity of AO for RNA species. Quantitative analysis of double‐labeled sections demonstrated that approximately 80% of TS‐positive NFTs also were AO‐positive, whereas approximately 55% of TS‐stained SPs contained AO labeling. These novel observations demosntrate the presence of RNAs in NFTs, NTs, and SPs.
Imaging of axonal damage in multiple sclerosis: Spatial distribution of magnetic resonance imaging lesions
Authors: Narayanan S. , Fu L. , Pioro E. , De Stefano N. , Collins D. L. , Francis G. S. , Antel J. P. , Matthews P. M. , Arnold D. L. 
Published: January 2005

AbstractWe performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2‐weighted magnetic resonance images, and lesion distribution images were generated for each patient. The conventional magnetic resonance and spectroscopic images were transformed into a standard brain‐based stereotaxic coordinate space, allowing comparison of images from different patients on a voxel‐by‐voxel basis. The spatial distribution of lesions in the transformed magnetic resonance images did not differ significantly between the relapsing and the progressive disease groups. We then generated from the individual data sets, group lesion probability distribution images for the relapsing and the progressive disease groups. The spatial distribution of metabolites was characterized with respect to lesion distribution using the magnetic resonance spectroscopic images transformed into stereotaxic space and averaged. The neuronal marker N‐acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects. Comparison of the averaged metabolite and T2‐weighted lesion probability images confirmed loss of N‐acetylaspartate in regions of both high and low lesion probability. This suggests that diffuse axonal volume loss or dysfunction extends beyond the inflammatory lesions of multiple sclerosis, perhaps due to microscopic disease or wallerian degeneration along projection pathways of axons traversing the lesions.