bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymerase chain reaction—based detection of Tropheryma whippelii in central nervous system Whipple's disease
Authors: Lynch T. , Odel J. , Fredericks D. N. , Louis E. D. , Forman S. , Rotterdam H. , Fahn S. , Relman D. A. 
Published: January 2005

AbstractWhipple's disease of the central nervous system (CNS) may be associated with normal intestinal histology as a result of minimal or patchy involvement. The diagnosis is difficult and is frequently made post mortem. We studied 6 patients with clinically suspected CNS Whipple's disease; 2 had oculomasticatory myorhythmia (OMM) fitting criteria for a diagnosis of definite CNS Whipple's disease. One of the 2 had duodenal histology highly suggestive of Whipple's disease; the other 5 patients had normal duodenal histology. DNA was extracted from paraffin‐embedded duodenal tissues in all patients and frozen pontine tissue in 1. Two primer pairs (WF‐WR, W3F‐W2R) were used in separate polymerase chain reactions (PCRs) to amplify fragments of Tropheryma whippelii 16S rDNA from these tissue samples. PCR amplicons were detected only in the duodenal tissues from the 2 patients with OMM. The sequences of these amplicons were identical to the corresponding region of the previously published Tropheryma whippelii 16S rDNA sequence. PCR‐based assays of intestinal or brain tissue may be of value for confirming, and possibly refuting, a clinical diagnosis of CNS Whipple's disease in a patient with any combination of dementia, supranuclear gaze palsy, hypothalamic manifestations, myoclonus, seizures, ataxia, or OMM, especially when tissue histology is unrevealing.
Effect of Lambert‐Eaton myasthenic syndrome antibodies on autonomic neurons in the mouse
Authors: Waterman Sally A. , Lang Bethan , Newsom‐Davis John 
Published: January 2005

AbstractSomatic muscle weakness and autonomic symptoms characterize the autoimmune Lambert‐Eaton myasthenic syndrome (LEMS). The former results from IgG autoantibody–mediated down‐regulation of P/Q‐type voltage‐gated calcium channels at motor nerve terminals and consequent reduction in acetylcholine release; the basis for the autonomic symptoms is unknown. Using ω‐conotoxins GVIA and MVIIC and ω‐agatoxin IVA that block N‐, Q‐, and P‐type channels, we investigated ex vivo the calcium channels subserving transmitter release from postganglionic parasympathetic neurons in the bladder and from postganglionic sympathetic neurons in the vas deferens of mice injected with IgG from LEMS patients or from controls. Calcium influx through N‐, P‐, and Q‐type channels subserved transmitter release from parasympathetic and sympathetic neurons in control mice. In test mice, the component of transmitter release subserved by P‐type channels was abolished by four of four LEMS IgG preparations, that subserved by Q‐type channels was significantly reduced by three, and that subserved by N‐type channels by one. Thus, LEMS IgG impairs transmitter release from parasympathetic and sympathetic neurons through down‐regulation of one or more subtypes of voltage‐gated calcium channels. The results suggest that antibody‐mediated interference with specific ion channel function may also underlie autonomic dysfunction occurring in other autoimmune diseases.
Hippocampal N‐acetylaspartate in neocortical epilepsy and mesial temporal lobe epilepsy
Authors: Vermathen Peter , Ende Gabriele , Laxer Kenneth D. , Knowlton Robert C. , Matson Gerald B. , Weiner Michael W. 
Published: January 2005

AbstractPrevious magnetic resonance spectroscopy (MRS) studies have shown that N−acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE). The reason for the contralateral damage is not clear. To test whether the hippocampus is also damaged if the focus is outside the hippocampus, we have measured patients with neocortical epilepsy (NE). Therefore, the goals of this study were to determine if hippocampal NAA is reduced in NE and if hippocampal NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10 NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16 controls. The results show that, in contrast to mTLE, NAA was not reduced in the hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure focus. These results suggest that repeated seizures do not cause secondary damage to the hippocampus. The absence of spectroscopic differences in NE may help to distinguish NE from mTLE.
Glial cell line–derived neurotrophic factor–levodopa interactions and reduction of side effects in parkinsonian monkeys
Authors: Miyoshi Yasuyuki , Zhang Zhiming , Ovadia Aliza , Lapchak Paul A. , Collins Frank , Hilt Dana , Lebel Carl , Kryscio Richard , Gash Don M. 
Published: January 2005

AbstractGlial cell line–derived neurotrophic factor (GDNF) stimulates the nigrostriatal dopaminergic pathway and improves motor functions in animal models of parkinsonism. Sinemet is currently the most widely used drug for treating Parkinson's disease. The present study has evaluated GDNF–Sinement interactions in parkinsonian rhesus monkeys. Both GDNF and Sinemet, when given alone, significantly improved total parkinsonian scores. The response to Sinement did not change after intracerebroventricular vehicle injections. In contrast, there was a functional interaction between GDNF and levodopa. When comparing the levodopa dose response before and after GDNF treatment, significant behavioral improvements were seen after trophic factor administration at every levodopa dose level except 500 mg. Adverse responses to Sinemet treatment alone in parkinsonian animals included vomiting, dykinesias, dystonias, and stereotypic movements. Combined GDNF–Sinemet treatment significantly reduced the occurrence of these levodopa‐induced side effects, with a >90% decrease in adverse responses seen at the mid‐Sinemet (250 mg levodopa–25 mg carbidopa) dose level. The only side effect from GDNF treatment was a transitory weight loss. Thus, combined GDNF–Sinemet treatment could be of therapeutic value in treating parkinsonism, by producing a greater functional response and by mitigating adverse responses to Sinemet treatment.
Central levodopa metabolism in Parkinson's disease after administration of stable isotope—labeled levodopa
Authors: Durso Raymon , Evans James E. , Josephs Ephraim , Szabo George K. , Evans Barbara A. , Handler Joseph S. , Jennings Dana , Browne Thomas R. 
Published: January 2005

AbstractWe report the use of a new stable isotope–labeled form of levodopa (LD) to examine in vivo central LD metabolism in Parkinson's disease (PD). Eight patients representing a wide spectrum of disease severity were administered 50 mg of carbidopa orally followed in 1 hour by an intravenous bolus of 150 mg of stable isotope–labeled LD (ring‐1′,2′,3′,4′,5′,6′‐13C6). Serial blood samples were taken every 30 to 60 minutes and a lumbar puncture was performed 6 hours after the infusion. The average percentage of labeled homovanillic acid (HVA) in lumbar cerebrospinal fluid (CSF) was 54% (SD, 9%; range, 34–67%). The mean CSF labeled HVA concentration was 34.7 ng/ml (SD, 20.2 ng/ml; range, 11.3–67.9 ng/ml). Area under the curve for labeled serum LD closely predicted CSF labeled HVA concentrations (r = 0.747, p = 0.033). Labeled CSF HVA levels did not significantly correlate with either quality or duration of response to the labeled LD dose. In a similar manner, labeled CSF HVA concentrations were not influenced by duration of disease or previous daily LD dosage. These findings support the hypothesis that levodopa‐induced benefit in PD is not severely limited by a defect in central levodopa metabolism.
Congenital axonal neuropathy caused by deletions in the spinal muscular atrophy region
Authors: Korinthenberg R. , Sauer M. , Ketelsen U.‐P. , Hanemann C. O. , Stoll G. , Graf M. , Baborie A. , Volk B. , Wirth B. , Rudnik‐Schöneborn S. , Zerres K. 
Published: January 2005

AbstractThree newborn siblings presented with generalized weakness, asphyxia, facial diplegia, and external ophthalmoplegia. Electrophysiological testing showed inexcitability of motor and sensory nerves and myographic signs of denervation. Nerve biopsies and postmortem examination showed loss of myelinated fibers and axonal damage in sensory and mixed nerves. Many spinal motor neurons were chromatolytic although their number was normal. Molecular genetic investigations revealed a homozygous deletion of the survival motor neuron (SMN) gene and a loss of markers Ag1‐CA and C212 in the paternal haplotype. These findings are consistent with the diagnosis of an unusually severe type of spinal muscular atrophy. Given the large extent of the deletion, it must be considered that the unusual severe phenotype with involvement of brainstem nuclei and afferent nerves might also be due to changes of yet unknown genes neighboring the SMN gene.
Factor V Leiden mutation: An unrecognized cause of hemiplegic cerebral palsy, neonatal stroke, and placental thrombosis
Authors: Thorarensen Olafur , Ryan Stephen , Hunter Jill , Younkin Donald P. 
Published: January 2005

AbstractActivated protein C resistance caused by an Arg506Gln mutation in the factor V gene (factor V Leiden mutation) is the most common cause of familial thrombosis. This mutation is associated with arterial and venous thromboembolic disease in neonates, infants, and children, but is not a significant risk factor for ischemic stroke in adults. We report on 3 babies with different neonatal cerebrovascular disorders including ischemic infarction and hemorrhagic stroke who are heterozygous for factor V Leiden mutation. One infant had multiple thrombi in the fetal placental vasculature. This is the first reported association between hemiplegic cerebral palsy, placental thrombosis, and factor V Leiden mutation. We suspect that activated protein C resistance may be an important cause of in utero cerebrovascular disease and hemiplegic cerebral palsy.
Recommendations from the national multiple sclerosis society clinical outcomes assessment task force
Authors: Rudick Richard , Antel Jack , Confavreux Christian , Cutter Gary , Ellison George , Fischer Jill , Lublin Fred , Miller Aaron , Petkau John , Rao Stephen , Reingold Stephen , Syndulko Karl , Thompson Alan , Wallenberg Joy , Weinshenker Brian , Willoughby Ernest 
Published: January 2005

AbstractThis article provides recommendations from the National Multiple Sclerosis Society's Clinical Outcomes Assessment Task Force. The Task Force was appointed in 1994 and charged with recommendending improved approaches for clinical outcomes assessment in future controlled clinical trials. The recommendations herein follow extensive deliberation and data analysis during 2.5 years. General principles and desirable measurement attributes were used to assess alternative measurement techniques and clinical scales. On the basis of the analysis of existing multiple sclerosis (MS) data sets, a new measurement approach is proposed. The approach is based on quantitative functional composites that consist of simple quantitative measures from the major clinical dimensions of MS combined into a single score. Quantitative functional composites are likely to provide improved precision and sensitivity in future MS clinical trials. Studies necessary to further refine quantitative functional composites as useful MS clinical trial outcomes are delineated.
Dietary fat intake and the risk of incident dementia in the Rotterdam study
Authors: Kalmijn Sandra , Launer Lenore J. , Ott Alewijn , Witteman Jacqueline C. M. , Hofman Albert , Breteler Monique M. B. 
Published: January 2005

AbstractA high intake of saturated fat and cholesterol and a low intake of polyunsaturated fatty acids have been related to an increased risk of cardiovascular disease. Cardiovascular disease has been associated with dementia. We investigated the association between fat intake and incident dementia among participants, age 55 years or older, from the population‐based prospective Rotterdam Study. Food intake of 5,386 nondemented participants was assessed at baseline with a semiquantitative food‐frequency questionnaire. At baseline and after an average of 2.1 years of follow‐up, we screened for dementia with a three‐step protocol that included a clinical examination. The risk of dementia at follow‐up (RR [95% CI]) was assessed with logistic regression. After adjustment for age, sex, education, and energy intake, high intakes of the following nutrients were associated with an increased risk of dementia: total fat (RR = 2.4 [1.1–5.2]), saturated fat (RR = 1.9 [0.9–4.0]), and cholesterol (RR = 1.7 [0.9–3.2]). Dementia with a vascular component was most strongly related to total fat and saturated fat. Fish consumption, an important source of n‐3 polyunsaturated fatty acids, was inversely related to incident dementia (RR = 0.4 [0.2–0.9]), and in particular to Alzheimer's disease (RR = 0.3 [0.1–0.9]). This study suggests that a high saturated fat and cholesterol intake increases the risk of dementia, whereas fish consumption may decrease this risk.
Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21–22
Authors: Baker Matt , Kwok John B. J. , Kucera Steve , Crook Richard , Farrer Matthew , Houlden Henry , Isaacs Adrian , Lincoln Sarah , Onstead Luisa , Hardy John , Wittenberg Leonie , Dodd Peter , Webb Sonja , Hayward Nick , Tannenberg Tony , Andreadis Athena , Hallupp Marianne , Schofield Peter , Dark Frances , Hutton Michael 
Published: January 2005

AbstractAn Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty‐eigth affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 · 8.9 years). We mapped the disease locus to an approximately 26‐cM region of chromosome 17q21–22 with a maximum two‐point LOD score of 2.87. Affected individuals share a common haplotype between markers D17S783 and D17S808. This region of chromosome 17 contains the loci for several neurodegenerative diseases that lack distinctive pathological features, suggesting that these dementias, collectively referred to as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP‐17), are caused by mutations in the same gene. The entire coding region of five genes, mapped to the FTDP‐17 candidate region, were also sequenced. This analysis included the microtubule‐associated protein tau that is the major component of the paired helical filaments observed in Alzheimer's disease. No pathogenic mutations were identified in either the tau gene or in any of the other genes analyzed.
Aging and the brain: A new frontier
Authors: Drachman David A. 
Published: January 2005

AbstractWith aging, both “normal” senescent age‐related changes (ARCs) and late‐onset diseases affect the brain, producing declines in performance. The brain as a postmitotic structure is particularly vulnerable to ARCs, and senescence is by far the most powerful risk factor for neurological diseases of the elderly such as sporadic Alzheimer's disease. The concept of senescence as an immutable result of the passage of time is yielding to understanding of the biology of ARCs. Both individual and species differences in longevity illustrate the variable effects of time. Whereas human life expectancy has been extended by prevention and treatment of specific diseases, life span can be altered by modifying the processes producing ARCs. Models of prolonged life span (eg, modifications of Caenorhabditis elegans longevity genes, restricted caloric intake)demonstrate the feasibility of extending longevity throughout the phylogenetic spctrum. Both programmed and variable factors produce ARCs. Cell survival depends on a balance of opposing factors–oncogene and anti‐oncogene products, cyclins, growth factors, and so on; apoptotic death results when the balance shifts. Variable factors, including accumulation of oxygen free radicals, protein conformational changes, decline in chaperone functions, and secondary loss of mitochondrial energy production, can also result in neuronal degeneration. To prevent the increased neuronal vulnerability of senescence, ARCs must be modified. The “new frontier” in neurology is the challenge of understanding the changes of aging, both to determine their impact on disease and to prevent their consequences.
Spinocerebellar ataxia type 6: CAG repeat expansion in α1a voltage‐dependent calcium channel gene and clinical variations in japanese population
Authors: Ikeuchi Takeshi , Takano Hiroki , Koide Reiji , Igarashi Shuichi , Tanaka Hajime , Tsuji Shoji , Takahashi Hitoshi , Horikawa Yoh , Honma Yoshiaki , Onishi Yoji , Nakao Naoki , Sahashi Ko , Tsukagoshi Hiroshi , Inoue Kiyoharu 
Published: January 2005

AbstractAutosomal dominant spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. Recently, mild CAG repeat expansion in the α1A voltage‐dependent calcium channel gene has been found to be associated with a type of autosomal dominant SCA (SCA6). We analyzed 98 Japanese families with autosomal dominant SCAs, for whom CAG repeat expansions of the SCA1, SCA2, Machado‐Joseph disease/SCA3, and dentatorubral‐pallidoluysian atrophy genes were excluded, and 5 apparently sporadic cases of cortical cerebellar atrophy. The diagnosis of SCA6 was confirmed in 30 families (31%) comprising 47 affected individuals and 1 sporadic case. The size of expanded CAG repeats ranged from 21 to 26 repeat units and was found to be correlated inversely with age at onset. We identified 2 SCA6 patients homozygous for expanded CAG repeats, whose ages at onset were earlier than the 95% lower confidence level, suggesting the presence of a gene dosage effect of expanded CAG repeat. Ataxia is the most common initial symptom found in 45 of the 48 patients. Patients with a prolonged disease course showed other accompanying clinical features including dystonic postures, involuntary movements, and abnormalities in tendon reflexes.
Increased serum levels of soluble CD95 (APO‐1/Fas) in relapsing‐remitting multiple sclerosis
Authors: Zipp Frauke , Weller Michael , Calabresi Peter A. , Frank Joseph A. , Bash Craig N. , Dichgans Johannes , McFarland Henry F. , Martin Roland 
Published: January 2005

AbstractCD95/CD95 ligand interactions are critically involved in the negative regulation of peripheral T‐cell responses. Here, we report that serum levels of soluble CD95 are significantly elevated in patients with relapsing remitting multiple sclerosis. In a transectional study, CD95 levels did not correlate with clinical disability or lesion formation on magnetic resonance imaging. Longitudinally, Expanded Disability Status Scale changes were associated with high CD95 levels. Interferon‐β (IFNβ) treatment led to an initial increase and subsequent decline of serum CD95 levels. Interestingly, patients generating neutralizing antibodies to the drug had significantly higher baseline CD95 levels before IFNβ treatment than those without neutralizing antibodies.
Upregulation of Fas/Fas ligand in inclusion body myositis
Authors: Fyhr Ing‐Marie , Oldfors Anders 
Published: January 2005

AbstractIn inclusion body myositis, T cells invade and destroy nonnecrotic muscle fibers. The mechanism by which T cells damage muscle fibers in inflammatory myopathies is not known. In this study we have investigated the expression of Fas and Fas ligand in muscle in five patients with inclusion body myositis. Reverse transcription polymerase chain reaction showed upregulation of both Fas and Fas ligand in all inclusion body myositis patients. Immunohistochemical investigation showed expression of Fas ligand in many of the muscle infiltrating mononuclear cells. Fas was expressed both in mononuclear cells and on the surface of muscle fibers in inclusion body myositis patients and in patients with polymyositis but not in patients with Duchenne muscular dystrophy or denervation. The results indicate that the Fas/Fas ligand system may be of importance for the inflammatory reaction and T‐cell–mediated muscle cell injury.
Gene transfer to schwann cells after peripheral nerve injury: A delivery system for therapeutic agents
Authors: Sørensen Jesper , Haase Georg , Krarup Christian , Gilgenkrantz Helene , Kahn Axel , Schmalbruch Henning 
Published: January 2005

AbstractWe transferred a reporter gene to Schwann cells to test whether they might serve as an endoneurial delivery system for therapeutic proteins. A replication‐defective adenoviral vector carrying the gene for β‐galactosidase (lacZ) was injected into the distal segment of intact or crushed sciatic nerves of adult rats, and the expression of lacZ was histochemically assessed. Less than 1% of the Schwann cells became reactive in intact nerves, but up to 18% of the proliferating Schwann cells of injured nerves expressed lacZ. Gene expression decayed with time but might persist for up to 2 months. It was enhanced by immunosuppression: daily cyclosporin A injections reduced both proliferation of Schwann cells and lymphocytic infiltration of the nerve, whereas tolerance induced by a single intrathymic injection of the vector 4 days after birth abolished the inflammatory response but not the proliferation of Schwann cells. The vector itself did not impede axonal regeneration. The results indicate that adenoviral gene transfer to Schwann cells in injured nerves is possible and suggest that induced production of neurotrophic factor may represent a therapeutic supplement to surgical nerve repair.
(R) salsolinol N‐methyltransferase activity increases in parkinsonian lymphocytes
Authors: Naoi Makoto , Maruyama Wakako , Nakao Naoki , Ibi Tohru , Sahashi Ko , Benedetti Margherita Strolin 
Published: January 2005

AbstractRecently, an endogenous catechol isoquinoline, 1(R),2(N)‐;6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline [N‐methyl(R)salsolinol], was proved to be a neurotoxin specific for dopamine neurons by in vivo and in vitro experiments. This N‐methyl(R)salsolinol was found to increase significantly in the cerebrospinal fluid of untreated parkinsonian patients, suggesting its possible involvement in the pathogenesis of Parkinson's disease. To clarify the mechanism of the increase, the activity of enzymes related to the metabolism of the neurotoxin was examined in lymphocytes prepared from parkinsonian patients and controls. In patients with Parkinson's disease, the activity of a neutral N‐methyltransferase, measured by using (R)salsolinol as a substrate, was found to increase significantly (100.2 ± 81.8 pmol/min/mg of protein) in comparison with that in controls (18.9 ± 15.0 pmol/min/mg of protein). The distribution of the activity was bimodal in the parkinsonian patients, whereas it was singular in controls. The activity of other related enzymes, an alkaline N‐methyltransferase and N‐methyl(R)salsolinol oxidase, in parkinsonian lymphocytes was the same as in controls. Increase of the neutral N‐methyltransferase may be an endogenous factor in the pathogenesis of Parkinson's disease.
Increased Aβ42(43) from cell lines expressing presenilin 1 mutations
Authors: Mehta Nitin D. , Refolo Lawrence M. , Eckman Chris , Sanders Sunny , Yager Debra , Perez‐Tur Jordi , Younkin Steve , Duff Karen , Hardy John , Hutton Mike 
Published: January 2005

AbstractMutations in the presenilin 1 (PS1) gene on chromosome 14 are a major cause of autosomal dominant, early‐onset Alzheimer's disease. Here, we show that transfecting cells with several mutant, but not wild‐type, PS1 cDNAs alters the processing of the amyloid precursor protein (APP) such that more Aβ42(43) is produced, confirming and extending several recent reports. The most effective mutation in this regard was the exon 9 splice‐out mutation (δ9). The correlation between the size of the effect on APP processing and the age of onset of disease assessed in families with the mutations was not informative, and the possible reasons for this are discussed.