bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dystonia gene in Ashkenazi Jewish population is located on chromosome 9q32–34
Authors: Kramer Patricia L. , De Leon Deborah , Ozelius Laurie , Risch Neil , Bressman Susan B. , Brin Mitchell F. , Schuback Deborah E. , Burke Robert E. , Kwiatkowski David J. , Shale Heidi , Gusella James F. , Breakefield Xandra O. , Fahn Stanley 
Published: January 2005

AbstractIdiopathic torsion dystonia (ITD) is a neurological disorder characterized by sustained muscle contractions that appear as twisting movements of the limbs, trunk, and/or neck, which can progress to abnormal postures. Most familial forms of ITD follow autosomal dominant transmission with reduced penetrance. The frequency of ITD in the Ashkenazi Jewish population is five to ten times greater than that in other groups. Recently, a gene for ITD (DYT1) in a non‐Jewish kindred was located on chromosome 9q32–34, with tight linkage to the gene encoding gelsolin (GSN). In the present study linkage analysis using DNA polymorphisms is used to locate a gene responsible for susceptibility to ITD in 12 Ashkenazi Jewish families. This dystonia gene exhibits close linkage with the gene encoding argininosuccinate synthetase (ASS), and appears by multipoint analysis to lie in the q32–34 region of chromosome 9, a region that also contains the loci for gelsolin and dopamine‐beta‐hydroxylase. The same gene may be responsible for ITD both in the non‐Jewish kindred mentioned above and in the Ashkenazi Jewish families presented here. However, because there is substantial difference between the penetrance of the dominant allele in these two groups, two different mutations may be operating to produce susceptibility to this disease in the two groups.
Increased thymocyte differentiation in myasthenia gravis: A dual‐color immunofluorescence phenotypic analysis
Authors: Durelli L. , Massazza U. , Poccardi G. , Ferrio M. F. , Cavallo R. , Maggi G. , Casadio C. , Di Summa M. , Bergamini L. 
Published: January 2005

AbstractThymocytes express multiple, different surface antigens according to their stage of maturation. Surface differentiation antigens have been studied with the technique of simultaneous dual‐color, direct immunofluorescence in the thymuses of 20 patients with myasthenia gravis (MG) and 10 control subjects with cardiac diseases. Fluorescein isothiocyanate‐conjugated and phycoerythrin‐conjugated monoclonal antibodies were used to stain thymic cell suspensions. A significant decrease in the percentage of immature and common thymocyte phenotypes (CD1+,3+ and CD4+,8+) and significant increase in the percentage of mature thymocyte phenotypes (CD1‐,3+; CD4+,8‐; and CD4‐,8+) and of B cells (CD20+) were found in MG thymuses compared with controls. These data, indicating an increased availability of mature, fully immunocompetent T and B cells, indirectly suggest the occurrence of an active immune response in MG thymus.
Neural transplantation using temperaturesensitive immortalized neural cells: A preliminary report
Authors: Bredesen Dale E. , Hisanaga Kinya , Sharsp Frank R. 
Published: January 2005

AbstractCurrent approaches to neural transplantation–adrenal medullary and fetal brain–suffer from limitations in tissue availability, cellular uniformity, and general applicability. The system described here uses temperature‐sensitive immortalized clonal neural cells to address these limitations. Cerebellar cells, immortalized with a temperature‐sensitive tumor virus, are transformed at 34°C, but differentiate at 38°C. The cells were genetically engineered to express beta‐galactosidase, providing a tag to study their fate in the host. The cells were then successfully transplanted to the cerebellum of adult rats.
The role of interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system
Authors: Hartung Hans‐Peter , Schäfer Bärbel , Van Der Meide Peter H. , Fierz Walter , Heininger Kurt , Toyka Klaus V. 
Published: January 2005

AbstractThe role of interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system was investigated. Administration of rat recombinant interferon‐gamma markedly augmented both myelin‐induced and T‐cell line‐mediated experimental autoimmune neuritis. Conversely, in vivo application of a monoclonal antibody to interferon‐gamma suppressed the disease. Clinical and electrophysiological findings were corroborated by semiquantitative morphometric analysis. Mechanisms responsible for the enhancing effects of interferon‐gamma include upregulation of major histocompatibility complex class II antigen expression in the nerve lesion, increased cellular influx of T cells and macrophages, and heightened macrophage activity with enhanced release of toxic oxygen species. These observations establish a pivotal role of the cytokine interferon‐gamma in the pathogenesis of experimental autoimmune disease of the peripheral nervous system.
The distribution of chromogranin A—like immunoreactivity in the human hippocampus coincides with the pattern of resistance to epilepsy‐induced neuronal damage
Authors: Munoz David G. 
Published: January 2005

AbstractThe distribution of chromogranin A‐like immunoreactivity in the hippocampus of adult humans who were free of neurological disease was examined by immunohistochemical methods. Immunoreactivity was restricted to the cytoplasm of certain neuronal populations, most notably the mossy fibers of dentate granule cells (and a subset of their perikarya), and the perikarya of pyramidal cells of the cornu Ammonis 2 (CA2) sector. Additionally, staining was observed in neurons in the stratum oriens, a population of neurons at the periphery of the CA4 sector, scattered, probably short‐axon perikarya in the CA1 sector, and fibers in the perforant path and the molecular layer of the dentate gyrus. Pyramidal neurons in the CA1 and CA3 sectors were not immunoreactive. The two prominently immunoreactive neuronal populations, CA2 pyramids and dentate granule cells, are those spared in human and experimental epileptic brain damage, whereas CA1 and CA3 pyramids, lacking chromogranin, are characteristically destroyed in this condition. The known activities of chromogranin in the periphery as a calcium‐binding protein and as a precursor of active peptides (autocrine inhibitory modulators) suggest that its distribution in the hippocampus may help to explain the observed pattern of resistance to epileptic brain damage.
Ataxic sensory neuropathy and dorsal root ganglionitis associated with Sjögren's syndrome
Authors: Griffin J. W. , Cornblath D. R. , Alexander E. , Campbell J. , Low P. A. , Bird S. , Feldman E. L. 
Published: January 2005

AbstractThirteen patients, 11 women and 2 men, developed sensory and autonomic neuronopathies in association with features of primary Sjögren's syndrome. In 11 Sjögren's syndrome had not been previously diagnosed at the time of neurological presentation. All had prominent loss of kinesthesia and proprioception. Pain and thermal sensibility were less serverely affected. Most had evidence of autonomic insufficiency. In some this was servere, with Adie's pupils, fixed tachycardia, and orthostatic hypotension. The course ranged from an abrupt, devastating onset to indolent progression over years. Stabilization or functional improvement occurred in 6 patients, 2 of whom received no drug therapy. Sensory nerve conduction studies and examination of nerve biopsy specimens demonstrated a wide spectrum in the severity of loss of large myelinated fibers. The cutaneous nerves of 6 patients had perivascular mononuclear infiltrates without necrotizing arteritis. Examination of biopsy specimens of dorsal root ganglia in 3 patients revealed lymphocytic (T‐cell) infiltration in the dorsal roots and ganglia, with focal clusters around neurons. In the more mildly affected ganglia, individual sensory neurons were undergoing degeneration. In the most advanced case, very few neurons remained. The possibility of Sjögren's syndrome should be considered in patients, especially women, who develop acute, subacute, or chronic sensory and autonomic neuropathies, with ataxia and kinesthetic loss.
Lower motor neuron syndromes defined by patterns of weakness, nerve conduction abnormalities, and high titers of antiglycolipid antibodies
Authors: Pestronk A. , Chaudhry V. , Feldman E. L. , Griffin J. W. , Cornblath D. R. , Denys E. H. , Glasberg M. , Kuncl R. W. , Olney R. K. , Yee W. C. 
Published: January 2005

AbstractWe studied 74 patients with progressive, asymmetrical lower motor neuron syndromes. Clinical features of these patients, including age, sex, disease duration, patterns of weakness, and reflex changes, were evaluated by review of records. In each patient the clinical features were compared to the type of nerve conduction abnormalities and to the specificities of high‐titer serum antiglycolipid antibodies. Antibody specificities were determined by an enzyme‐linked immunosorbent assay using purified glycolipids and carbohydrates as substrates. Our results show that high titers of antibodies to glycolipids are common in sera of patients with lower motor neuron syndromes. Selective patterns of reactivity indicate that specific carbohydrate epitopes on the glycolipids are the targets of the high‐titer antibodies in individual patients with lower motor neuron syndromes. Several distinct lower motor neuron syndromes can be identified based on clinical, physiological, and antiglycolipid antibody characteristics. These syndromes include multifocal motor neuropathy with evidence of multifocal conduction block on motor, but not sensory, axons and frequent (84 ) high titers of anti‐GM1 ganglioside antibodies; a lower motor neuron syndrome with predominantly distal weakness early in the disease course, no conduction block, and a high incidence (64%) of anti‐GM1 antibodies; and a lower motor neuron syndrome with predominant early weakness in proximal muscles and serum antibodies to asialo GM1 that do not cross‐react with GM1 ganglioside.
Eyelid twitching seizures and generalized tonic‐clonic convulsions: A syndrome of idiopathic generalized epilepsy
Authors: Miller John W. , Ferrendelli James A. 
Published: January 2005

AbstractThis is a report of two neurologically normal patients who had primary generalized seizures consisting of irregular fluttering or twitching movements of the eyelids accompanied by generalized, rhythmic 9‐ to 15‐Hz electroencephalographic discharges as well as infrequent generalized tonic‐clonic seizures. This is a syndrome of idiopathic generalized epilepsy that responds to treatment with valproic acid.
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
Authors: DeKosky Steven T. , Scheff Stephen W. 
Published: January 2005

AbstractUltrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD) revealed that the number of synapses in lamina III of Brodmann's area 9 was significantly decreased when compared with the number in age‐matched control brains (n = 9; postmortem time, < 13 hours). Further decline in synaptic number was seen in age‐matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini‐Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini‐Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined. The loss of neuronal connectivity, indexed by loss of synapses, predicted the degree of cognitive impairment in the patients who underwent biopsy and indicated a degree of structural change in AD brain not likely to be affected by pharmacotherapy.
Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: A randomized, double‐blinded, placebo‐controlled clinical trial
Authors:   The Multiple Sclerosis Study Group, Wolinsky  
Published: January 2005

AbstractPatients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2‐year, double‐blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole‐blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 ± 1.07 grades for cyclosporine‐treated patients and 0.65 ± 1.08 grades for placebo‐treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for “time to sustained progression” or on a composite score of “activities of daily living.” Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine‐treated patients, 32% for placebo‐treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant.
N‐Methyl‐D‐Aspartate antagonist reduces stroke size and regional glucose metabolism
Authors: Simon Roger , Shiraishi Kazuya 
Published: January 2005

AbstractPharmacological inhibition of cell excitation during focal ischemia was studied in the rat middle cerebral artery occlusion model. The potent and selective N‐methyl‐D‐aspartate antagonist CGS 19755, administered 5 minutes prior to or 5 minutes following permanent middle cerebral artery occlusion, caused a substantial decrease in infarct size, which was associated with reduction of postischemic cerebral glucose hypermetabolism. These data support a role for excitation‐induced hypermetabolism in the pathogenesis of infarction following focal cerebrovascular occlusion.
Nationwide survey of HTLV‐I–associated myelopathy in Japan: Association with blood transfusion
Authors: Osame Mitsuhiro , Janssen Robert , Kubota Hiroaki , Nishitani Hiroshi , Igata Akihiro , Nagataki Shigenobu , Mori Masataka , Goto Ikuo , Shimabukuro Hiromi , Khabbaz Rima , Kaplan Jonathan 
Published: January 2005

AbstractTo study the epidemiology of human T‐cell lymphotropic virus type I (HTLV‐I)–associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Japan, we conducted two nationwide surveys between October 1986 and March 1989. A total of 710 patients with HAM (definite HAM, 589; probable HAM, 121) were reported. Of the 589 patients with definite HAM, 69%0 were residents of the areas with the highest prevalence HTLV‐I in Japan. To determine the importance of blood transfusion in the pathogenesis of HAM/TSP, we performed a case‐control study in the Kagoshima district in southern Japan. Significantly more patients with HAM reported a history of blood transfusion (26/129, or 20%) than did subjects in a health survey of the general population (41/1,290, or 3%; odds ratio = 7.7, p < 0.001) or than did hospitalized neurological patients (6/119, or 5%; odds ratio = 4.8, p < 0.001). Furthermore, the cumulative percentages of the intervals between blood transfusion and the onset of the symptoms of HAM fit a lognormal curve, suggesting that transfusion was an important common exposure. Blood transfusion probably transmitted HTLV‐I to the patients with transfusion‐associated HAM because there was a significant decrease in the number of patients with the transfusion‐associated HAM who received blood after implementation of nationwide screening of blood donors in 1986 (p = 0.004). In the first 2 years, screening the blood supply in Japan appears to have decreased the number of reported patients with HAM by 16%.
Macrophages but not schwann cells express ia antigen in experimental autoimmune neuritis
Authors: Schmidt Beate , Stoll Guido , Hartung Hans‐Peter , Heininger Kurt , Schäfer Bärbel , Toyka Klaus V. 
Published: January 2005

AbstractThis study was designed to identify which cells express major histocompatibility complex class II (Ia) antigen in experimental autoimmune neuritis and may therefore be antigen presenters. Serial 1‐μm‐thick cryosections of ventral roots of animals with experimental autoimmune neuritis were labeled with Ox6 antibody against rat Ia, the ED1 antibody to identify monocytes/macrophages and an antiserum against S100, a marker for Schwann cells. Ia‐positive cells were predominantly present before overt clinical signs and demyelination (day 12). At later stages when many axons were demyelinated, their number was markedly reduced. Few Ia‐positive cells that had extending long processes, which over some distance were in immediate contact with several myelin sheaths, were scattered in normal‐appearing nerve roots at these later time points. Most of the Ia‐positive cells could be identified as ED1‐positive leanmonocytes/macrophages, but in contrast most phagocytic macrophages in advanced stages of myelin degradation no longer expressed Ia. Ia‐positive structures were invariably negative for S100 at early and late stages of experimental autoimmune neurities, indicating that Schwann cells did not express identifiable Ia antigen. These findings contrast with reports of expression of major histocompatibility complex class II antigens by Schwann cells in human neuropathies. Furthermore they do not support the notion that aberrant Ia expression by Schwann cells plays a major pathogenic role in experimental autoimmune disease of the peripheral nervous system.
Chronic encephalitis, epilepsy, and cerebrovascular immune complex deposits
Authors: Andrews John M. , Thompson Joel A. , Pysher Theodore J. , Walker Marian L. , Hammond M. Elizabeth 
Published: January 2005

AbstractRefractory epilepsy, electroencephalographic abnormalities, progressive hemiplegia, and contralateral hemicerebral atrophy developed in a previously healthy 3‐year, 9‐month‐old girl. Extensive laboratory testing showed elevated serum antinuclear antibody titers, cerebrospinal fluid oligoclonal bands, and elevated immunoglobulin G (IgG): albumin ratio, IgG index, and IgG synthesis rate: Pathological study of a subtotal hemispherectomy specimen revealed widespread cerebral vasculitis with immunofluorescence staining for IgG, IgM, IgA, C3, and C1q, and ultrastructural evidence of vascular injury in addition to severe cortical atrophy with marked neuronal loss. Cerebrospinal fluid abnormalities in other reported patients siuggest that immunological abnormalities may not be unique to this girl. These data suggest possible immunopathogenetic mechanisms in these patients.
DNA cytosine methylation in brain of patients with Alzheimer's disease
Authors: Schwob Netanel G. , Nalbantoglu Josephine , Hastings Kenneth E. M. , Mikkelsen Tom , Cashman Neil R. 
Published: January 2005

AbstractWe developed a novel quantitative assay to test the hypothesis that defects in DNA cytosine methylation might be responsible for the brain chromatin abnormalities and transcriptional alterations observed in patients with Alzheimer's disease (AD). We found no significant difference in percent methylation of CCGG sites from brain DNA of 44 patients with AD compared with 20 normal subjects. These results, however, would not exclude genomic redistribution of methylcytosine in AD, or disturbed methylation of a limited population of critical brain‐specific genes.
Dissociated neglect behavior following sequential strokes in the right hemisphere
Authors: Daffner Kirk R. , Ahern Geoffrey L. , Weintraub Sandra , Mesulam M‐Marsel 
Published: January 2005

AbstractA 42‐year‐old woman suffered two focal right hemisphere strokes, sequentially damaging different components of a proposed cerebral network for the spatial distribution of attention. Her first stroke was centered in the right frontal lobe and resulted in left hemispatial neglect but only for tasks that emphasize exploratory‐motor components of directed attention. A second stroke occurred 20 days later in the parietal lobe and led to the emergence of perceptual‐sensory aspects of neglect. This case strongly supports the existence of a distributed anatomic‐functional network subserving directed attention.
A clinical triad to diagnose paraneoplastic retinopathy
Authors: Jacobson Daniel M. , Thirkill Charles E. , Tipping Stuart J. 
Published: January 2005

AbstractTwo elderly men developed photosensitivity and light‐induced glare, transient visual symptoms, and progressive visual loss several months before small cell carcinoma of the lung was discovered. Both patients had impaired visual acuity and color vision, ring scotomas, and attenuated retinal arteriole caliber. Electroretinography demonstrated abnormal cone and rod‐mediated responses. Antiretinal antibodies were identified in their serum. Their visual sensory function improved following therapy with immunosuppressive agents. The triad of photosensitivity, ring scotomatous visual field loss, and attenuated retinal arteriole caliber should alert one to a paraneoplastic disorder affecting the retina.
Ubiquitin immunoreactivity in kuru plaques in Creutzfeldt‐Jakob disease
Authors: Suenaga Toshihiko , Hirano Asao , Llena Josefina F. , Ksiezak‐Reding Hanna , Yen Shu‐Hui , Dickson Dennis W. 
Published: January 2005

AbstractCerebellar kuru plaques in 2 cases of Creutzfeldt‐Jakob disease were studied immunohistochemically. Similar to cerebellar senile plaques in Alzheimer's disease, many kuru plaques contained ubiquitin‐positive, tau‐negative small granular elements, presumably representing dystrophic neurites. Our results suggest that similar mechanisms are involved in neuritic changes in cerebellar plaques in Creutzfeldt‐Jakob and Alzheimer's diseases despite differences of amyloid proteins in the plaques.