bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial parkinsonism, dementia, and lewy body disease: Study of family G
Authors: Denson Melody A. , Wszolek Zbigniew K. , Pfeiffer Ronald F. , Wszolek Elzbieta K. , Paschall Tanya M. , McComb Rodney D. 
Published: January 2005

AbstractGenetic influences are thought by many to play an important role in the cause of Parkinson's disease. We studied two closely intermarried families (Family G) whose ancestors immigrated to the United States from Russia. We investigated this family clinically, genealogically, and pathologically. Our pedigree contained 102 members spanning six generations, with 10 affected individuals and 1 affected spouse. Detailed telephone interviews were conducted with affected individuals, with their spouses, and with their at‐risk siblings. Medical records of deceased and living affected patients were collected. Physical examinations were performed on 7 at‐risk and 5 affected persons. Typical levodopa‐responsive parkinsonism with bradykinesia, rigidity, resting tremor, and impaired postural reflexes was seen in 4 members, dementia was present in 3, and 3 had both dementia and parkinsonism. An autopsy completed on 1 individual, our index case, demonstrated Lewy bodies in the brainstem and neocortex and ubiquitin‐positive neuritic degeneration in the CA2–3 region of the hippocampus, consistent with the limbic (transitional) form of Lewy body disease. This family is distinct both clinically and pathologically from several previously reported parkinsonian kindreds.
Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome
Authors: Ellis Ronald J. , Hsia Karen , Spector Stephen A. , Nelson Julie A. , Heaton Robert K. , Wallace Mark R. , Abramson Ian , Atkinson J. Hampton , Grant Igor , McCutchan J. Allen 
Published: January 2005

AbstractTo determine whether cerebrospinal fluid (CSF) viral burden measurements can assist in the evaluation of human immunodeficiency virus (HIV)‐associated neurocognitive disorders, we quantified HIV type 1 (HIV‐1) RNA in CSF. Because previous findings suggested that disease stage, lymphocytic pleocytosis, and HIV‐1 RNA levels in plasma may influence CSF viral burden, these variables were examined as potential modifying factors. HIV‐1 RNA levels were quantified by using a reverse transcriptase–polymerase chain reaction assay. Performance on a comprehensive neuropsychological (NP) battery was noted in 97 prospectively enrolled, HIV‐infected subjects. Among subjects with acquired immunodeficiency syndrome (AIDS) (<200 CD4 lymphocytes), NP impairment was associated with significantly higher CSF RNA levels (3.1 vs 1.8 log10 copies/ml; p = 0.02); most impaired subjects met criteria for HIV‐associated dementia or minor cognitive–motor disorder. In subjects without AIDS, CSF RNA and NP impairment were unrelated. Before AIDS, CSF RNA was strongly correlated to plasma RNA and to pleocytosis, but in AIDS, CSF and plasma RNA were independent. In conclusion, we found elevated CSF HIV‐1 RNA levels in NP impaired subjects with AIDS. Before AIDS, systemic viral replication, possibly through CD4+ mononuclear cell trafficking, may govern virus levels in CSF, whereas in AIDS, CD4 cell depletion may unmask a correlation between increased productive central nervous system HIV infection and clinical neurocognitive disorders.
Relationship between human immunodeficiency virus—associated dementia and viral load in cerebrospinal fluid and brain
Authors: McArthur Justin C. , McClernon Daniel R. , Cronin Michael F. , Nance‐Sproson Tish E. , Saah Alfred J. , St Clair Marty , Lanier E. Randall 
Published: January 2005

AbstractCerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA levels were measured with the Nucleic Acid Sequence‐Based Amplification (NASBA) assay to determine the relationship with neurological status; 37 subjects with HIV dementia (HIV‐D) were compared with 77 with HIV with minor neurological signs (HIV‐MCMD) and 93 neurologically normal HIV‐seropositive individuals (HIV‐NML). The NASBA assay had a lower limit of detection of 100 copies per milliliter. Mean CSF log HIV RNA levels were significantly higher in those with dementia after adjusting for CD4 count and were correlated with dementia severity. Plasma levels did not distinguish comparably immunosuppressed subjects with or without dementia. CSF and plasma RNA levels were significantly intercorrelated for subjects with CD4 counts <200/mm3 and also correlated inversely with CSF β2‐microglobulin. CSF RNA levels were independent of CSF pleocytosis or antiretroviral exposure. Brain RNA levels were consistently higher than CSF but correlated with CSF values for dementia subjects. The NASBA assay can be used reliably to determine HIV RNA levels in CSF, brain, and plasma samples. CSF HIV RNA may be a surrogate marker for brain infection, based on the observed correlation with brain levels. The association between plasma HIV RNA and CSF levels of HIV and β2‐microglobulin suggests that both viral load and CNS immune activation are important determinants of neurological disease.
Proton magnetic resonance spectroscopic imaging and magnetic resonance imaging volumetry in the lateralization of temporal lobe epilepsy: A series of 100 patients
Authors: Cendes Fernando , Caramanos Zografos , Andermann Frederick , Dubeau François , Arnold Douglas L. 
Published: January 2005

AbstractSurgery is a safe and effective treatment for drug‐resistant temporal lobe epilepsy (TLE). However, bilateral electroencephalographic (EEG) abnormalities are frequently present, making presurgical lateralization difficult. New magnetic resonance (MR) techniques can help; proton magnetic resonance spectroscopic imaging (MRSI) can detect and quantify focal neuronal damage or dysfunction based on reduced signals from the neuronal marker N‐acetylaspartate, and magnetic resonance imaging (MRI)‐based measurements of amygdala‐hippocampal volumes (MRIVol) can improve the detection of atrophy of these structures. We performed proton MRSI and MRIVol in 100 consecutive patients with medically intractable TLE to determine how well these techniques agreed with the lateralization by extensive EEG investigation. We found that the EEG, MRSI, and MRIVol findings were highly concordant. The MRSI was abnormal in 99 of 100 patients (bilateral in 54%). The MRIVol was abnormal in 86 of 98 patients (bilateral in 28%). We obtained lateralization in 83% of patients using MRIVol alone, in 86% using MRSI alone, and in 90% by combining MRSI and MRIVol (vs 93% lateralization by EEG). MRSI was abnormal in 12 patients with normal MRIVol. The combination of proton MRSI and MRIVol can lateralize TLE accurately and noninvasively in the great majority of patients. By reducing reliance on EEG, these imaging techniques could reduce prolonged presurgical evaluation and make seizure surgery available to more patients.
Correlation between PMP‐22 messenger mRNA expression and phenotype in hereditary neuropathy with liability to pressure palsies
Authors: Schenone Angelo , Nobbio Lucilla , Caponnetto Claudia , Abbruzzese Michele , Gherardi Gianfranco , Mancardi Gianluigi , Mandich Paola , Bellone Emilia , Ajmar Franco , Windebank Anthony J. 
Published: January 2005

AbstractHereditary neuropathy with liability to pressure palsies (HNPP) is associated with a deletion in chromosome 17p 11.2, which includes the gene for the peripheral myelin protein 22 (PMP‐22). A “gene dosage” effect is probably the mechanism underlying HNPP, but the amount of PMP‐22 mRNA in sural nerves of HNPP patients is highly variable and the role of PMP‐22 underexpression in impairing myelination has yet to be clarified. We have studied 6 genetically proven HNPP patients, to evaluate the relationship between PMP‐22 mRNA levels, and clinical, neurophysiological, and neuropathological findings. Underexpression of PMP‐22 mRNA correlates with disease severity and with mean axon diameter and g ratio, but not with myelin thickness, number of “tomacula,” or nerve conduction parameters. Our findings further confirm that underexpression of PMP‐22 is the main pathogenetic mechanism underlying the severity of clinical symptoms and signs in HNPP. Smaller axons in sural nerves of HNPP patients with lower PMP‐22 levels suggests that underexpression of PMP‐22 may also affect axon development.
Morphometry of in vivo human white matter association pathways with diffusion‐weighted magnetic resonance imaging
Authors: Makris N. , Worth A. J. , Papadimitriou G. M. , Stakes J. W. , Caviness V. S. , Kennedy D. N. , Pandya D. N. , Kaplan E. , Sorensen A. G. , Wu O. , Reese T. G. , Wedeen V. J. , Rosen B. R. , Kennedy D. N. , Davis T. L. 
Published: January 2005

AbstractThe precise characterization of cortical connectivity is important for the understanding of brain morphological and functional organization. Such connectivity is conveyed by specific pathways or tracts in the white matter. Diffusion‐weighted magnetic resonance imaging detects the diffusivity of water molecules in three dimensions. Diffusivity in anisotropic in oriented tissues such as fiber tracts. In the present study, we used this method to map (in terms of orientation, location, and size) the “stem” (compact portion) of the principal association, projection, and commissural white matter pathways of the human brain in vivo, in 3 normal subjects. In addition, its use in clinical neurology is illustrated in a patient with left inferior parietal lobule embolic infarction in whom a significant reduction in relative size of the stem of the left superior longitudinal fasciculus was observed. This represents an important method for the characterization of major association pathways in the living human that are not discernible by conventional magnetic resonance imaging. In the clinical domain, this method will have a potential impact on the understanding of the diseases that involve white matter such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, head injury, and spinal cord injury.
Dendritic injury is a pathological substrate for human immunodeficiency virus—related cognitive disorders
Authors: Masliah Eliezer , Ellis Ronald J. , Mallory Margaret , Heaton Robert K. , Marcotte Thomas D. , Nelson Julie A. , Grant Igor , Atkinson J. Hampton , Wiley Clayton A. , Achim Cristian L. , McCutchan J. Allen 
Published: January 2005

AbstractTo determine the neuropathological substrate of human immunodeficiency virus (HIV)‐associated neurocognitive disorders, we examined persons with acquired immunodeficiency syndrome before their death and related their antemortem neuropsychological performance to postmortem indicators of HIV encephalitis, viral burden, and presynaptic and postsynaptic neuronal injury. Of 20 prospectively examined cases, 9 were neurocognitively normal, 5 showed neuropsychological impairment, 5 had minor cognitive/motor disorder, and 1 was demented. Degree of neurocognitive impairment was strongly related to the amount of dendritic simplification based on microtubule‐associated protein 2 immunohistochemical staining, somewhat less so to a semiquantitative viral burden score based on numbers of HIV gp41‐immunoreactive cells, and much less so to the presence of multinucleated giant cells or microglial nodules. It appears that even milder neurocognitive impairment reflects microneuroanatomical injury to synaptic structures.
Serial proton magnetic resonance spectroscopic imaging, contrast‐enhanced magnetic resonance imaging, and quantitative lesion volumetry in multiple sclerosis
Authors: Narayana Ponnada A. , Doyle Timothy J. , Lai Dejian , Wolinsky Jerry S. 
Published: January 2005

AbstractSerial magnetic resonnce (MR) studies that included proton MR spectroscopic imaging (MRSI), contrast‐enhanced MR imaging (MRI), and lesion volumetric studies were performed on 25 multiple sclerosis (MS) patients with mild to modest clinical deficits. Each patient was scanned at varying intervals for up to 2 years, resulting in a total of 124 usable MR sessions. In these longitudinal studies, metabolic changes were observed on MRSI for some subjects before the appearance of lesions on MRI scanning. Regional changes in metabolite levels were observed to be dynamic and reversible in some patients. Transient changes in N‐acetylaspartate (NAA) levels were sometimes found in acute plaques and indicate that a reduced NAA level does not necessarily imply axonal loss. An inverse correlation between the average NAA within the spectroscopic volume and the total lesion volume in the whole brain was observed. This negative correlation implies that NAA can serve as an objective marker of the disease burden. Strong lipid peaks in the absence of gadolinium enhancement and MRI‐defined lesions were observed in 4 patients. This observation suggests that demyelination can occur independent of perivenous inflammatory changes and supports the presence of more than one pathophysiological process leading to demyelination in MS.
A novel mutation in the mitochondrial tRNAVal gene associated with a complex neurological presentation
Authors: Tiranti Valeria , D'Agruma Leonardo , Pareyson Davide , Mora Marina , St Franco Carrara , Zelante Leopoldo , Gasparini Paolo , Zeviani Massimo 
Published: January 2005

AbstractWe describe a patient who presented with progressive ataxia, sezures, mental deterioration, mild myopathy, and hearing loss. A novel heteroplasmic G‐to‐A transition was found, affecting the acceptor stem of the mitochondrial (mt) tRNAVal gene. Mutant mtDNA was 67% of total mtDNA in the muscle of the proband and was also present at low levels in the muscle of his healthy mother. It was absent in all of the numerous control DNA samples that were tested. Analysis of single muscle fibers revealed a significantly greater level of mutant mtDNA in cytochrome c oxidase‐negative fibers. Mutations of mtDNA may be responsible of neurological syndromes that, like the case reported here, are clinically puzzling, and lack typical “mitochondrial” clues, such as elevated levels of blood lactate, overt defects of the respiratory complexes, and clinically documented maternal inheritance.
Loss of electrical excitability in an animal model of acute quadriplegic myopathy
Authors: Rich Mark M. , Pinter Martin J. , Kraner Susan D. , Barchi Robert L. 
Published: January 2005

AbstractIn rats treated with high‐dose corticosteroids, skeletal muscle that is denervated in vivo (steroid‐denervated [S‐D]) develops electrical inexcitability similar to that seen in patients with acute quadriplegic myopathy. In studies of affected muscles in vitro, the majority of S‐D fibers failed to generate action potentials in response to intracellular stimulation although the average resting potential of these fibers was no different from that of control denervated muscle. The downregulation of membrane chloride conductance (GC1) seen in normal muscle after denervation did not occur in S‐D muscle. Although block of chloride channels in S‐D muscle produced high specific membrane resistance, comparable to similarly treated control denervated muscle, and partially restored excitability in many fibers, action potential amplitude was still reduced in S‐D fibers, suggesting a concomitant reduction in sodium current. 3H‐saxitoxin binding measurements revealed a reduction in the density of the adult muscle sodium channel isoform in S‐D muscle, suggesting that a decrease in the number of sodium channels present may play a role in the reduction of sodium current, although altered properties of channels may also contribute. The weakness seen in S‐D muscle may involve the interaction of a number of factors that modify membrane excitability, including membrane depolarization, persistence of GC1, and reduced voltage‐gated sodium currents.
Cognitive, neuroimaging, and pathological studies in a patient with Pick's disease
Authors: Lieberman Andrew P. , Trojanowski John Q. , Lee Virginia M.‐Y. , Balin Brian J. , Ding Xin‐Shen , Greenberg Joel , Morrison Donald , Reivich Martin , Grossman Murray 
Published: January 2005

AbstractWe conducted cognitive, imaging, and neuropathological studies on a patient with Pick's disease. The patient was impaired at interpreting sentences with complex grammatical constructions, differing significantly from control subjects and patients with Alzheimer's disease (AD). Evaluation of regional brain functioning at rest, with positron emission tomography, revealed reduced left frontal activity compared with control subjects and AD patients. Autopsy demonstrated the classic pathology of Pick's disease, including massive neuron loss and gliosis in the frontal and cingulate cortex as well as numerous tau‐positive hippocampal Pick bodies. The abnormal tau proteins were phosphorylated at the same amino acid residues as AD paired helical filament tau (PHFtau), but they exhibited a unique migration profile on western blot. Our observations support the hypothesis that a distinct variety of hyperphosphorylated tau in Pick's disease compromises the long‐term viability of selectively vulnerable populations of neurons in frontal cortices that contribute to sentence processing.
Proinflammatory cytokines regulate antigen‐independent T‐cell Activation by two separate calcium‐signaling pathways in multiple sclerosis patients
Authors: Martino Gianvito , Grohovaz Fabio , Brambilla Elena , Codazzi Franca , Consiglio Antonella , Clementi Emilio , Filippi Massimo , Comi Giancarlo , Grimaldi Luigi M. E. 
Published: January 2005

AbstractCentral nervous system (CNS) lesions typical of multiple sclerosis (MS) are characterized by demyelinating inflammatory infiltrates that contain few CNS antigen‐specific autoreactive T cells and a multitude of pathogenic non‐antigen‐specific mononuclear cells. Here, we report that in patients with MS the combined action of interferon‐γ (IFNγ), tumor necrosis factor‐α (TNFα), interleukin (IL)‐2, and IL‐6 leads to the activation of most peripheral T cells (mainly CD4 memory) by promoting a persistent intracellular calcium increase via two independent signaling pathways. The activation of these pathways, one activated by IFNγ and the other by the combination TNFα/IL‐2/IL‐6, is independent from myelin antigens and precedes by 2 weeks phases of disease activity (eg, clinical relapses and/or appearance of gadolinium‐enhancing lesions on brain magnetic resonance imaging scans during 1 year of follow‐up). Our results indicate that an appropriate combination of the four cytokines, three with a proinflammatory profile and one necessary for T‐cell growth and differentiation, can activate in an antigen‐independent fashion most peripheral T cells from MS patients. This mechanism is likely to contribute to the recruitment of nonspecific lymphocytes into the cellular activation processes leading to CNS demyelination and may represent a major target for immune intervention in MS.
Cochlear origin of hearing loss in MELAS syndrome
Authors: Sue C. M. , Lipsett L. J. , Crimmins D. S. , DipAud C. S. Tsang , Boyages S. C. , Presgrave C. M. , Gibson W. P. R. , Byrne E. , Morris J. G. L. 
Published: January 2005

AbstractThere have been few studies investigating the mechanism and nature of the hearing loss that occurs in the mitochondrial disorders. We studied 18 patients with the MELAS A3243G point mutation from four different kindreds. Pure tone audiometry, speech discrimination testing, acoustic reflexes, tympanometry, and brain stem auditory evoked responses were performed to localize the site of pathology in the auditory pathways. In 12 patients, we performed electrocochleography and otoacoustic emissions to assess cochlear involvement. Neuroimaging and promontory nerve stimulation were performed to exclude retrocochlear pathology. Audiological testing confirmed sensorineural hearing loss in 14 of the 18 patients studied; hearing loss was usually gradual in onset, was symmetrical, and initially affected the higher frequencies. In some patients, there were features that distinguished the hearing loss from presbyacusis, including a young age at onset, asymmetrical involvement, stepwise progression, and partial recovery. We treated one patient who had profound bilateral hearing loss with cochlear implantion; this restored good functional hearing. Hearing loss in MELAS syndrome appears to be due to dysfunction of the cochlea, probably resultiong from metabolic failure of the stria vascularis and outer hair cells. Cochlear implantation is a therapeutic option worth considering in those patients who become deaf.
End‐plate voltage‐gated sodium channels are lost in clinical and experimental myasthenia gravis
Authors: Ruff Robert L. , Lennon Vanda A. 
Published: January 2005

AbstractThis study examined the loss of voltage‐gated Na+ channels as well as acetylcholine receptors (AChRs) form the endplate region in patients with acquired myasthenia gravis (MG) and in rats with experimental autoimmune passively transferred MG (PTMG). Rats received a monoclonal IgG antibody directed against an extracellular epitope of the nicotinc acetylcholine receptor of muscle (AChR) to produce PTMG. At the end‐plate border we examined miniature end‐plate potentials (MEPPs), sodium current (INa) amplitude, and action potential (AP) properties; the latter two were also examined on the extrajunctional membrane. In the normal situation, the safety factor for neuromuscular transmission is ensured by the large INa at the end plate, which reduces the AP threshold. Among different fiber types, INa was largest for type IIb fibers and smallest for type I fibers. When end‐plate border properties of fibers form 3 MG patients and 15 PTMG rats were compared with controls, INa was reduced, AP thresholds were higher, and rates of AP rise were reduced. Amplitudes of MEPPs and INa at the end plate indicated that loss of AChRs was greater than loss of Na+ channels in patients with MG and rats with PTMG; INa was reduced to about 60% of control values, whereas MEPPs were reduced to less than 30% of control values. On the extrajunctional membrane, INa and AP thresholds and rates ofrise were similar for MG patients, PTMG rats, and controls. This evidence for loss of voltage‐gated Na+ channels at the motor end plate in both patients with MG and in rats with PTMG reveals a hitherto unrecognized consequence of the end‐plate damage initiated by the binding of complement‐fixing IgG to end‐plate AChRs.
Selective inhibition of human glial inducible nitric oxide synthase by interferon‐β: Implications for multiple sclerosis
Authors: Hua Liwei L. , Liu Judy S. H. , Brosnan Celia F. , Lee Sunhee C. 
Published: January 2005

AbstractNitric oxide generated from the inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of multiple sclerosis. Because significant species‐ and cell‐specific differences exist in the expression of iNOS, we used primary human glial cell cultures to screen for an inhibitor of iNOS expression. Remarkably, among numerous soluble factors tested, interferon‐β (IFN‐β) alone showed a selective and potent inhibition of interleukin‐1β/interferon‐γ (IL‐1β/IFN‐)–induced iNOS expression in astrocytes. Inhibition of iNOS may provide a mechanism by which IFN‐β can ameliorate inflammation and cytotoxicity in the central nervous system of patients with multiple sclerosis.