bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human–severe combined immunodeficiency myasthenic mouse model: A new approach for the study of myasthenia gravis
Authors: Martino Gianvito , DuPont Bonita L. , Wollmann Robert L. , Bongioanni Paolo , Anastasi John , Quintans Josè , Arnason Barry G. W. , Grimaldi Luigi M. E. 
Published: January 2005

AbstractWe have established a new chimeric human‐mouse model of myasthenia gravis in severe combined immunodeficiency mice, using human peripheral blood lymphocytes that survive in the mouse and produce specific antibodies that mediate pathological changes typical of human myasthenia gravis. Mice given peripheral blood lymphocytes from both anti–acetylcholine receptor (AChR) antibody–positive and –negative patients with myasthenia gravis showed circulating anti–acetylcholine receptor antibodies, deposition of human IgG at muscle end‐plates, and simplification of the postsynaptic membrane, findings characteristic of human myasthenia gravis. Mice given human peripheral blood lymphocytes from healthy donors and simultaneously immunized with Torpedo acetylcholine receptor showed the same changes. This chimeric model, utilizing human cells to reproduce the immunopathological findings of human myasthenia gravis in a nonhuman environment, offers new opportunities to study immune regulation in autoimmunity.
Dopa resistance in multiple‐system atrophy: Loss of postsynaptic D2 receptors
Authors: Churchyard A. , Donnan G. A. , Hughes A. , Howells D. W. , Woodhouse D. , Wong J. Y. F. , Kalnins R. M. , Mendelsohn F. A. O. , Paxinos G. 
Published: January 2005

AbstractPostmortem autoradiography was used to explor the mechanisms underlying L‐dopa resistance in 2 patients with multiple‐system atrophy. Indices of striatal presynaptic dopamine terminal loss and dopamine (D1 and D2) receptors were provided by 3H‐SCH 23390, and 123I‐sulpiride binding. Neuronal loss, gliosis, and loss of postsynaptic D2 receptors preferentially involved the middle and posterior of the putamen, that region of the striatum most intimately involved in motor function. Loss of D1 receptors in the same area occurred in only 1 patient. These findings suggest that in multiple‐system atrophy, resistance to L‐dopa is due to a loss of putamental D2 receptors. The differential effects on D1 and D2 receptors in 1 patient implies that different subpopulations of striatal neurons were selectively involved.
Diffuse noxious inhibitory controls in humans: A neurophysiological investigation of a patient with a form of Brown‐Séquard syndrome
Authors: Bouhassira Didier , Le Bars Daniel , Bolgert Francis , Laplane Dominique , Willer Jean‐Claude 
Published: January 2005

AbstractIn normal subjects, the application of heterotopic painful stimuli induces simultaneous and parallel decrease in the sensation of pain and of the spinal nociceptive flexion (RIII) reflex evoked by electrical stimulation of the sural nerve. This inhibition of the RIII reflex is absent in tetraplegic patients with clinically complete spinal cord transections and can be triggered only from the analgesic hand in patients with Wallenberg's syndrome. These findings suggest that the inhibitory phenomena observed in normal subjects are likely to be examples of diffuse noxious inhibitory controls (DNICs), being sustained by a loop involving supraspinal structures, the ascending part of which is localized in the spinoreticular tract. We now report an exceptional case of a patient with Brown‐Séquard syndrome due to a 4‐year‐old spinal cord lesion (left side, T‐6 level) produced by a knife‐wound in the back. Nociceptive flexion (RIII) reflexes elicited by stimulation of cutaneous afferents in the ulnar and sural nerves were studied in the upper and lower limbs by recording from the biceps brachialis and biceps femoris muscles, respectively. For each limb, the RIII reflex threshold was determined. The reflex was then elicited regularly by stimuli of 1.2 times threshold before, during, and after periods of nociceptive electrical conditioning stimulation (15 mA; 4Hz; 1 min) applied successively to the other three limbs. Inhibitions of around 90% followed by after effects (2–3 min) were observed in all situations except that (1) no inhibition could be obtained when the conditioning stimuli were applied to the lower right limb (contralateral to the spinal lesion) and (2) the RIII reflex in the lower left limb was completely insensitive to any of the conditioning stimuli. These results suggest that in humans (1) the ascending part of the loop subserving DNICs is completely crossed at the spinal level and (2) the descending part is confined to the white matter ipsilateral to the limb being tested.
Long‐term follow‐up of 121 patients with benign fasciculations
Authors: Blexrud Marceil D. , Windebank Anthony J. , Daube Jasper R. 
Published: January 2005

AbstractUsing the case records of Mayo Clinic patients, 121 patients with a diagnosis of benign fasciculations were identified. All had a normal neurological examination and normal electrophysiological studies, except for fasciculation potentials. Interviews by telephone were conducted 2 to 32 years after diagnosis. None of the patients developed symptomatic motor neuron disease. Forty individuals were in health care careers. A subset of 19 patients described acute onset of fasciculations following a viral infection. Benign fasciculations are not a prelude to progressive motor neuron disease.
Quinolinic acid in children with congenital hyperammonemia
Authors: Batshaw Mark L. , Robinson Michael B. , Hyland Keith , Djali Sina , Heyes Melvyn P. 
Published: January 2005

AbstractLevels of the excitotoxin quinolinic acid (QUIN) were measured in the cerebrospinal fluid of infants and children with congenital hyperammonemia. Twofold to tenfold elevations of QUIN were found in 4 neonates in hyperammonemic coma (QUIN range, 250–990 nM; control mean, 110 ± 90 nM; p < 0.005). Similar elevations of neopterin were found (range, 24–75 nM; control mean, 9.0 ± 4.9 nM; p < 0.005). In addition, significant elevations of QUIN were found in 14 older children with congenital hyperammonemia (mean, 50 ± 20 vs 17 ± 6 nM; p < 0.05). Neopterin levels were not elevated in these children. The QUIN may originate from an increase in tryptophan transport across the blood‐brain barrier or from induction of indolamine‐2,3‐dioxygenase activity. These findings support a role for QUIN in the neuropathology of congenital hyperammonemia. They also suggest the potential utility of N‐methyl‐D‐aspartate receptor–‐blocking agents or inhibitors of QUIN synthesis in the treatment of hyperammonemic coma.
Herpes simplex type 2 in a patient with Mollaret's meningitis: Demonstration by polymerase chain reaction
Authors: Cohen Bruce A. , Rowley Anne H. , Long Christopher M. 
Published: January 2005

AbstractWe describe a patient with recurrent self‐limited aseptic meningitis meeting the criteria for Mollaret's syndrome, in whom extensive serological investigation and cerebrospinal fluid analysis failed to reveal a specific cause. Using polymerase chain reaction techniques to amplify herpes simplex viral DNA, we were able to identify the presence of herpes simplex virus type 2 in the cerebrospinal fluid. The duration of clinical illness may have been shortened by treatment with intravenous acyclovir. We suggest that herpes simplex virus may be a more common cause of aseptic meningitis than has been demonstrated by current commonly available serological and culture techniques.
Human β‐mannosidase deficiency associated with peripheral neuropathy
Authors: Levade T. , Graber D. , Flurin V. , Delisle M‐B. , Pieraggi M‐T. , Testut M‐F. , Carrière J‐P. , Salvayre R. 
Published: January 2005

AbstractHuman β‐mannosidosis is an inherited lysosomal storage disorder described in only seven families. We present a further case in a black African 14‐year‐old boy with severely deficient β‐mannosidase activity, bilateral thenar and hypothenar amyotrophy, electrophysiologically demonstrable demyelinating peripheral neuropathy, and cytoplasmic vacuolation of skin fibroblasts and lymphoid cells. The clinical and biochemical features of our patient are compared to those of previously reported patients.
Trial of immunosuppression in amyotrophic lateral sclerosis using total lymphoid irradiation
Authors: Drachman Daniel B. , Chaudhry Vinay , Cornblath David , Kuncl Ralph W. , Pestronk Alan , Clawson Lora , Mellits E. David , Quaskey Shirley , Quinn Thomas , Calkins Allison , Order Stanley 
Published: January 2005

AbstractAlthough the cause of amyotrophic lateral sclerosis (ALS) remains unknown, recent studies have suggested an autoimmune mechanism of pathogenesis. Previous trials of immunosuppressive treatment have yielded inconclusive results. Our study was designed to determine whether more powerful and prolonged immunosuppression, produced by total lymphoid irradiation (TLI), would alter the course of ALS. In a double‐blind, randomized, placebo‐controlled study, 30 patients with classic ALS were treated with TLI, and 31 were given sham radiation. Quantitative measurements of muscle strength, functional motor activity, and humoral and cellular immune status were followed for 2 years, or until death or respirator dependence. Motor function in the TLI‐treated and control groups showed no significant differences throughout the study. Overall survival was not significantly different in the TLI‐treated and control groups. TLI effectively suppressed cellular and humoral immune function throughout the 2‐year study period. Analysis of the relationship between immunosuppression and motor functions showed no consistent effect of treatment. We conclude that powerful and prolonged immunosuppression produced by TLI did not benefit patients with ALS. This fails to support the concept of an autoimmune mechanism of pathogenesis of ALS.
Ciliary neurotrophic factor: Pharmacokinetics and acute‐phase response in rat
Authors: Dittrich Falk , Theonen Hans , Sendtner Michael 
Published: January 2005

AbstractCiliary neurotrophic factor (CNTF) supports the survival of motoneurons in vitro and in vivo. Recombinant CNTF is an investigational drug for the treatmentof amyotrophic lateral sclerosis. We determined the pharmacokinetics of radioiodinated CNTF after intravenous injection into rats. CNTF shows a biphasic clearance with an initial plasma half‐life of 2.9 minutes and is removed from the circulation by the liver. No accumulation of radioactivity was detectable in nerve tissue or skeletal muscle after intravenous injection of 0.1 μg and 0.5 μg of CNTF. Radioactive degradation products accumulate in the skin. Liver cells express specific binding proteins for CNTF, and the incorporation and degradation of intravenously injected CNTF by the liver may occur after association of CNTF with the soluble CNTF receptor α in the circulation. Probably as a consequence of its binding to hepatocytes, CNTF induces acute‐phase responses in liver. The short half‐life and the inflammatory side effect may limit the clinical usefulness of systematically administered CNTF in the treatment of human motoneuron disorders.
Phosphorus magnetic resonance spectroscopic imaging in patients with frontal lobe epilepsy
Authors: Garcia Paul A. , Laxer Kenneth D. , van der Grond Jeroen , Hugg James W. , Matson Gerald B. , Weiner Michael W. 
Published: January 2005

AbstractPhosphorus magnetic resonance spectroscopic imaging has previously demonstrated localized metabolic abnormalities within the epileptogenic region in patients with temporal lobe epilepsy, including alkalosis, increased inorganic phosphate level, and decreased phosphomonoester levels. We studied 8 patients with frontal lobe epilepsy, finding interictal alkalosis in the epileptogenic region compared to the contralateral frontal lobe in all patients (7.10 ± 0.05 vs 7.00 ± 0.06, p < 0.001). Seven patients exhibited decreased phosphomonoester levels in the epileptogenic frontal lobe compared to the contralateral frontal lobe (16.0 ± 6.0 vs 23.0 ± 4.0, p < 0.01). In contrast to findings in temporal lobe epilepsy, inorganic phosphate level was not increased in the epileptogenic region. Based on values derived from normal control subjects, 5 patients had elevated pH in the seizure focus and 2 patients had decreased phosphomonoesters while none had abnormalities in the contralateral frontal lobe. These data suggest that magnetic resonance spectroscopy will be useful in the presurgical evaluation of patients with frontal lobe epilepsy.
Neuronal migration disorders: Positron emission tomography correlations
Authors: Lee Namsoo , Radtke Rodney A. , Gray Linda , Burger Peter C. , Montine Thomas J. , DeLong G. Robert , Lewis Darrell V. , Oakes W. Jerry , Friedman Allan H. , Hoffman John M. 
Published: January 2005

AbstractWe analyzed the interictal [18F]fluoro‐2‐deoxy‐D‐glucose positron emission tomography (PET) findings of 17 epileptic patients with neuronal migration disorders (NMDs). Fifteen patients had abnormal PET findings, i.e., focal hypometabolism in 9 patients and displaced metabolic activity of normal gray matter in 6. All 15 patients had magnetic resonance imaging (MRI) abnormalities; however, PET abnormality assisted in the identification of NMDs on MRI in 3 patients. Two patients with negative MRI also had negative PET studies. PET hypometabolism appeared to correlate with severity of neuronal dysgenesis or temporal lobe involvement, or both. Displaced metabolic activity of gray matter is regarded as a unique interictal [18F]fluoro‐2‐deoxy‐D‐glucose–PET finding in NMD. This study demonstrates variable metabolic patterns in NMD and that PET may be a useful complement to MRI in the evaluation of NMD.
Intravascular malignant lymphomatosis: Amelioration of neurological symptoms with plasmapheresis
Authors: Harris Cheryl P. , Sigman June D. , Jaeckle Kurt A. 
Published: January 2005

AbstractIntravascular malignant lymphomatosis is a rare disease that is uniformly fatal when disseminated. Chemotherapeutic and radiation therapy regimens have provided short‐term amelioration of symptoms but have not affected overall survival. We describe a patient with diffuse neurological symptoms who responded transiently but dramatically to plasmapheresis. This marked response warrants further evaluation of this therapy in intravascular malignant lymphomatosis.
FK506‐induced neurotoxicity in liver transplantation
Authors: Wijdicks Eelco F. M. , Wiesner Russell H. , Dahlke Linda J. , Krom Ruud A. F. 
Published: January 2005

AbstractWe report FK506‐induced neurotoxicity in 14 of 44 consecutive patients following orthoptic liver transplantation. In 10 of these 14 patients, postural hand tremors were found in the first weeks following surgery, transient apraxia of speech in 3, and generalized tonic‐clonic seizures were noted in 2 patients. Other manifestations included nightmares, agitation, and acute delirium. Reduction of the FK506 dose resulted in resolution of symptoms, but in 1 patient mild speech difficulties and in 3 patients a fine tremor remained. Blood and plasma levels of FK506 were similar in patients with and without neurotoxicity. FK506 neurotoxicity in patients with liver transplantation commonly results in transient neurological manifestations. The incidence of neurotoxicity in FK506 is dramatically reduced in maintenance doses of 0.075 mg/kg twice a day.
Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease
Authors: Simpson Ian A. , Chundu Koteswara R. , Davies‐Hill Theresa , Honer William G. , Davies Peter 
Published: January 2005

AbstractGlucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both transporters were reduced in the cerebral cortex, with larger and highly significant reductions observed for GLUT3, the putative neuronal glucose transporter. The reductions in GLUT3 were greater than the loss of synapses, and should be considered as a potential cause of the deficits in glucose metabolism.
Wearing‐off fluctuations in Parkinson's disease: Contribution of postsynaptic mechanisms
Authors: Bravi D. , Mouradian M. M. , Roberts J. W. , Davis T. L. , Sohn Y. H. , Chase T. N. 
Published: January 2005

AbstractWearing‐off phenomenon that complicates levodopa therapy of Parkinson's disease has been attributed to a reduction in striatal dopamine storage due to the progressive degeneration of presynaptic dopaminergic terminals. To determine whether postsynaptic mechanisms also contribute to these response fluctuations, the duration of the antiparkinsonian response in parkinsonian patients grouped by disease severity was compared following discontinuation of a steady‐state optimal‐dose infusion of apomorphine. Although the plasma half‐life of this dopamine receptor agonist remained constant, its mean efficacy half‐time declined from 66 minutes in early, levodopa‐naive patients to 33 minutes in advanced, complicated parkinsonians (p < 0.005). Since the motor effects of apomorphine do not depend on the presence of dopaminergic terminals, changes at the postsynaptic level undoubtedly contribute to the diminished response duration. The only slightly greater attenuation of levodopa's motor effects observed previously under similar conditions suggests these postjunctional alterations, possibly involving relatively plastic striatal dopaminoceptive systems, account for most of the shortening in the duration of levodopa action that underlie wearing‐off fluctuations.
Responsiveness of the somatosensory system after nerve injury and amputation in the human hand
Authors: Schady W. , Braune S. , Watson S. , Torebjörk H. E. , Schmidt R. 
Published: January 2005

AbstractWe studied the responsiveness of the somatosensory system in humans after prolonged deprivation of peripheral input. Eight patients with traumatic transection of the median or ulnar nerve and 6 patients with amputation of a finger or hand underwent microneurography and intraneural stimulation. Bundles of nerve fibers were electrically stimulated through a microelectrode placed in the affected nerve proximally to the site of damage or in the case of amputees, in a nerve fascicle supplying the stump. During intraneural stimulation the subjects with nerve injuries reported distinct percepts in the hypoesthetic skin. Their projections were usually confined to the territory of a single or two adjacent palmar digital nerves, similar to the fascicular territories of healthy nerves in control subjects, but there was much less microneurographically recordable afferent activity than in normal subjects. In amputees intraneural stimulation evoked sensations in a phantom digit or digits in over three fourths of the fascicles studied. We conclude that (1) the somatosensory system remains able to process information from a nerve fascicle that has lost its cutaneous territory, and (2) somatosensory localization remains accurate despite the presumed central reorganization that takes place after nerve division or amputation. This lack of functional adaptation has important implications with regard to our understanding of human central nervous system plasticity.
Parkinson's disease and brain levels of organochlorine pesticides
Authors: Fleming Lora , Mann John B. , Bean Judy , Briggle Thomas , Sanchez‐Ramos Juan R. 
Published: January 2005

AbstractEpidemiological studies have suggested an etiologic relationship between pesticide exposure and Parkinson's disease (PD). Organochlorine pesticides were assayed in postmortem brain samples from 20 PD, 7 Alzheimer's disease (AD), and 14 nonneurological control cases. The three groups were similar in age at death, sex, and demographic variables. Only two of 16 pesticide residues screened were detected. A long‐lasting residue of DDT (pp‐DDE) was found in the majority of cases of PD and AD, as well as in all the control cases; pp‐DDT was significantly more likely to be found in AD controls than the PD cases (Fisher's exact two‐tailed, p = 0.04). Dieldrin was detected in 6 of 20 PD brains, 1 of 7 AD, and in none of 14 control samples. Despite the relatively small number of brains assayed, the association between Dieldrin and the diagnosis of PD was highly significant (p = 0.03). Dieldrin, a lipid‐soluble, long‐lasting mitochondrial poison, should be investigated as a potential etiological agent of Parkinsonism.
Sequence heterogeneity of HTLV‐I proviral DNA in the central nervous system of patients with HTLV‐I–associated myelopathy
Authors: Kira Jun‐ichi , Koyanagi Yoshio , Yamada Takeshi , Itoyama Yasuto , Tateishi Jun , Akizuki Shin‐ichiro , Kishikawa Masao , Baba Eishi , Nakamura Minoru , Suzuki Jun , Nakamura Tatsufumi , Nakamura Naomi , Yamamoto Naoki , Goto Ikuo 
Published: January 2005

AbstractThe nucleotide sequence of human T‐lymphotropic virus type I (HTLV‐I) in central nervous system tissue was determined in 3 autopsy cases with HTLV‐I–associated myelopathy (HAM)/tropical spastic paraparesis (TSP) and 1 seropositive carrier without HAM/TSP but with multiple sclerosis. All HAM/TSP samples (3 spinal cords and 2 brains) and the sample from the seropositive carrier without HAM/TSP (brain) were positive for HTLV‐I env (5146–6681), pX5′ (6549–7494), and pX3′ (7354–8276) regions by the two‐step polymerase chain reaction method. A nucleotide sequence analysis of the pX5′ and pX3′ polymerase chain reaction products from nucleotides 6631 to 8259 revealed heterogeneity of the HTLV‐I genome in all cases. It is notable that 13 of 50 clones derived from the pX3′ polymerase chain reaction products were defective in the tax open reading frame while 7 were defective in the rex open reading frame in the HAM/TSP samples. All 17 clones from 1 HAM/TSP case were defective in the pX open reading frame II. One nucleotide insertion at 7784 creating a frame shift in both tax and rex was seen in all 3 HAM/TSP cases but not in the HTLV‐I carrier without HAM/TSP. The pX‐defective mutants found frequently in the central nervous system may contribute to the neural damage, since the pX gene products are essential for the transactivation of various cellular genes as well as for viral replication.
X‐linked pachygyria and agenesis of the corpus callosum: Evidence for an X chromosome lissencephaly locus
Authors: Berry‐Kravis Elizabeth , Israel Jeanette 
Published: January 2005

AbstractA family of 5 affected male infants in 2 generations with an X‐linked pattern of inheritance is described. All affected infants manifested intractable seizures, severe psychomotor retardation, growth failure, microphallus, and death during infancy. Three of the affected patients had radiological studies that demonstrated findings consistent with pachygyria‐agyria and agenesis of the corpus callosum. We believe that this family represents a form of X‐linked pachygyria‐agyria (lissencephaly) that has not been described previously and suggests a locus for lissencephaly on the X chromosome.