bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordance of T‐cell receptor β‐chain genes in familial multiple sclerosis
Authors: Lynch Sharon G. , Rose John W. , Petajan Jack H. , Stauffer Dora , Kamerath Craig , Leppert Mark 
Published: January 2005

AbstractRestriction fragment length polymorphisms of the T‐cell receptor β‐chain gene were studied in DNA obtained from 96 individuals from 14 multiplex families with multiple sclerosis (MS). Thirty‐four family members had definite MS and two had probable MS. Five normal family members had abnormal findings on cranial magnetic resonance imaging (MRI) scans. Linkage analysis was performed using the Bgl II and the KpnI polymorphisms. With penetrance values from 0.1 to 0.7, and altering the scoring of the normal individuals with abnormal findings on MRI scans from “unknown” to “affected,” log of the odds scores between −4.59 to −12.76 were found for the autosomal dominant model. For the autosomal recessive model with a penetrance range from 0.1 to 1.0, the LOD scores ranged from −8.20 to −32.98. These findings do not support a direct role of T‐cell receptor β‐chain gene in the inheritance of MS.
Abnormal dopamine uptake sites in postmortem striatum from patients with tourette's syndrome
Authors: Singer Harvey S. , Hahn In‐Hei , Moran Timothy H. 
Published: January 2005

AbstractThe dopamine hypothesis for Tourette's syndrome proposes that the disorder is pathologically related either to an excessive amount of dopamine or to supersensitive receptors. To evaluate these proposals, pre‐ and postsynaptic markers of dopamine metabolism were measured in postmortem striatum from three adults with the diagnosis of Tourette's syndrome. Neuronal dopamine uptake carrier sites ([3H]mazindol binding) were significantly increased in number over control values by 37% in the caudate and by 50% in the putamen. High‐pressure liquid chromatographic assays of dopamine and its primary metabolites, homovanillic acid and 3,4‐dihydroxyphenylacetic acid, showed normal findings. D1 and D2 subtypes of dopaminergic receptors ([3H]SCH 23390 and [3H]spiperone binding, respectively) showed only slight alterations, presumably due to treatment with neuroleptics. The concentration of adenosine 3′,5′‐ monophosphate (cyclic AMP) in putamen was reduced by 23%. Our data support earlier proposals of a dopaminergic abnormality in TS, but suggest that the mechanism involves a significant alteration of uptake sites. We spéculate that increases in carrier site binding indicate an enhanced dopamine innervation within the striatum.
Is the carboxyl‐terminus of dystrophin required for membrane association? A novel, severe case of duchenne muscular dystrophy
Authors: Hoffman Eric P. , Garcia Carlos A. , Chamberlain Jeffrey S. , Angelini Corrado , Lupski James R. , Fenwick Raymond 
Published: January 2005

AbstractDuchenne muscular dystrophy is a lethal X‐linked recessive disorder caused by the deficiency of a component of the muscle fiber membrane cytoskeleton called dystrophin. Becker muscular dystrophy, a clinically milder disorder, results from dystrophin abnormalities rather than deficiency. We identified the first patient who is clearly an exception to these established clinical and biochemical correlates. The patient described clinically had particularly severe Duchenne dystrophy. Biochemically, his muscle contained substantial amounts of abnormal dystrophin (Becker‐like). Characterization of the dystrophin protein and gene revealed a unique intragenic gene deletion resulting in a dystrophin protein missing the carboxyl‐terminal domain. This patient's dystrophin seemed to have a deleterious “dominant” effect on his muscle: The presence of this abnormal protein was more damaging to the myofibers than the absence of dystrophin would have been. This patient challenges the current hypothesis that dystrophin associates with the plasma membrane solely via its carboxyl‐terminus, yet supports the hypothesis that an intact carboxyl‐terminus is crucial for correct dystrophin function.
Recombinant human nerve growth factor infusions prevent cholinergic neuronal degeneration in the adult primate brain
Authors: Tuszynski Mark H. , Sang U Hoi , Yoshida Kazunari , Gage Fred H. 
Published: January 2005

AbstractAtrophy of cholinergic neurons is a prominent component of Alzheimer's disease, and may explain in part the profound memory loss that is characteristic of patients with this disorder. Previous studies in animal models have shown that infusions of nerve growth factor into the adult brain can prevent both age‐related and lesion‐induced cholinergic neuronal atrophy. Recently, recombinant human nerve growth factor was found biologically active in nonprimate animal models. In the present experiment, recombinant human nerve growth factor infusions into the brains of adult primates prevented lesion‐induced cholinergic neuronal degeneration and promoted cholinergic neurite sprouting. These findings provide additional support for potential therapeutic trials of human nerve growth factor in patients with Alzheimer's disease.
Parametric in vivo imaging of benzodiazepine receptor distribution in human brain
Authors: Frey Kirk A. , Holthoff Vjera A. , Koeppe Robert A. , Jewett Douglas M. , Kilbourn Michael R. , Kuhl David E. 
Published: January 2005

AbstractEmission computed tomographic methods for the in vivo quantification of radioligand‐binding sites in human brain have previously been limited either by a lack of correction for possible effects of altered ligand transport or by highly complicated physiological models that preclude display of binding data in a detailed anatomical format. We investigated the application of a simplified compartmental model to the kinetic analysis of in vivo ligand binding to central benzodiazepine receptors. The human brain distribution of {11C}flumazenil, as determined by dynamic positron emission tomography, combined with metabolite‐corrected arterial blood samples, permitted estimations of local cerebral ligand transport and of receptor binding. This approach allows calculation of transport and binding “maps” on a pixel‐by‐pixel basis, resulting in the display of binding data in a familiar tomographic format while maintaining much of the physiological accuracy inherent in more complex methods. The results obtained in a study of 6 normal volunteers revealed good interindividual precision, with coefficients of variation between 10 and 15% of mean regional values, suggesting the utility of this approach in future clinical studies of benzodiazepine receptor binding.
Anti—tumor necrosis factor therapy abrogates autoimmune demyelination
Authors: Selmaj K. , Raine C. S. , Cross A. H. 
Published: January 2005

AbstractTo define a role for the cytokine tumor necrosis factor (TNF) in immune‐mediated demyelination, the effect of anti‐TNF antibody was investigated with a form of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice induced by the adoptive transfer of myelin basic protein‐(MBP)‐sensitized T lymphocytes, an animal model of the human disease multiple sclerosis (MS). In three separate experiments, no mouse sensitized for EAE and then treated with anti‐TNF by intraperitoneal injection developed signs of central nervous system (CNS) disease. Examination of CNS tissue from anti‐TNF‐treated animals showed no pathological changes. CNS tissue from control animals demonstrated extensive inflammatory cell infiltration and demyelination. To test whether anti‐TNF therapy was inhibitory to encephalitogenic cells, preincubation of MBP‐sensitized T lymphocytes with anti‐TNF in vitro prior to injection into recipient mice was performed, and resulted in no diminution of their ability to transfer EAE. In addition, spleen cells from anti‐TNF‐ treated mice were capable of serial transfer of EAE, similar to spleen cells from control animals. However, spleen cells from anti‐TNF‐treated mice did not produce TNF on stimulation with MBP or concanavalin A. This study showed that anti‐TNF antibody can inhibit effectively the development of EAE by interfering with the effector, rather than the induction, phase of the disease. Anticytokine therapy may have important applications in the development of new therapeutic strategies for MS.
The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine‐depleted rats and MPTP‐treated monkeys
Authors: Klockgether Thomas , Turski Lechoslaw , Honoré Tage , Zhang Zhiming , Gash Don M. , Kurlan Roger , Greenamyre J. Timothy 
Published: January 2005

AbstractAbnormally increased subthalamic nucleus output to the internal pallidal segment and the reticular part of the substantia nigra plays a critical pathophysiological role in the development of parkinsonism. Because synaptic transmission of subthalamic output is glutamatergic and mediated, in part, by the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)subtype of glutamate receptor, AMPA receptor antagonists may posses antiparkinsonian properties. We report that in monoamine‐depleted rats, 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo(f)quinoxaline (NBQX) (Novo‐Nordisk, Copenhagen, Denmark)—a selective antagonist of the AMPA subtype of glutamate receptor—suppressed muscular rigidity but had no effect on akinesia. NBQX microinjected into the subthalamic nucleus, internal pallidal segment, and reticular part of the substantia nigra, but not into the laterodorsal neostriatum of the rats, stimulated locomotor activity and reduced muscular rigidity. In aged Rhesus monkeys with bilateral 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydrophyridine‐induced parkinsonism intramuscular NBQX produced clinically apparent improvement in akinesia, tremor, posture, and gross motor skills. NBQX also potentiated the antiparkinsonian effects of L‐3,4‐dihydroxyphenylalanine in both rats and monkeys. Blockade of excitatory synaptic transmission by AMPA receptor antagonists may provide a new therapeutic strategy for Parkinson's disease (PD).
Brain amino acid reductions in one family with chromosome 6p—linked dominantly inherited olivopontocerebellar atrophy
Authors: Kish Stephen J. , Robitaille Yves , El‐Awar Munir , Gilbert Joseph , Deck John , Chang Li‐Jan , Schut Lawrence 
Published: January 2005

AbstractWe measured the levels if aspartate, glutamate, gamma‐aminobutyric acid (GABA), and other amino acids in autopsied brain of 6 patients from one family (Pedigree S) with dominantly inherited olivopontocerebellar atrophy. A previous demonstration of redeuced aspartate concentration in plasma of affected members of this family suggested the possibility of a generalized disorder of amino acid metabolism affecting the brain. As compared with the control levels, mean levels of aspartate and glutamate were markedly reduced by about 70 and 40°, respectively, in the degenerated cerebellar cortex from the patients. Since the cerebellar asparate reduction liekly exceeds the amount that could be explained by neuronal loss, other factors such as abnormal asparate metabolism, neurotransmitter turnover, or both are probably involved. Mean aspartate, glutamate, and GABA levels were also reduced by about 10 to 30° in most of the 16 examined extracerebellar brain areas in which no or, at most, mild neuronal cell loss was observed by semiquantitative estimation. Concentrations of taurine, glutamine, and o‐phosphoethanolamine were normal in all brain areas examined. Our biochemical data provide support to the presence of a generalized, but quantitatively mild, disturbance in amino acid metabolism in patients with olivopontocerebellar atrophy from Pedigree S. The regionally widespread amino acid reductions in the brain, of as yet unknown pathophysiological significance, could be due to a failure of one or more enzymes involved in aspartate and glutamate metabolism.
MK‐801 and ketamine induce heat shock protein HSP72 in injured neurons in posterior cingulate and retrosplenial cortex
Authors: Sharp Frank R. , Jasper Pat , Hall John , Noble Linda , Sagar Stephen M. 
Published: January 2005

AbstractMK‐801 and ketamine are noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor blockers that decrease brain injury in animal models of focal and global ischemia. Recent reports, however, suggested that MK‐801 itself can damage neurons. Here we show that MK‐801 (0.1 to 5.0 mg/kg) and ketamine (40 to 100 mg/kg) typically induce heat shock protein HSP72 mainly in layer 3 neurons of the posterior cingulate and retrosplenial cortex of the rat. These HSP72‐immunoreactive neurons contain abnormal cytoplasmic vacuoles visualized by electron microscopy. The HSP72 immunoreactivity is maximal at 24 hours with 1.0‐mg/kg doses of MK‐801 and disappears by 2 weeks. Based on these data, we propose: (1) MK‐801 and ketamine injure selected neurons, which express HSP72 in response to that injury. (2) Since HSP72 is induced for 1 to 2 weeks, the prolonged psychological side effects of MK‐801, ketamine, phencyclidine, and related drugs could be related to this injury. (3) The neuroprotective effect of MK‐801 is probably not related to HSP72 induction. (4) HSP72 immunocytochemistry is useful for studying nonlethal neuronal injury from a wide variety of brain insults.
The prevalence of vascular dementia in europe: Facts and fragments from 1980–1990 studies
Authors: Rocca Walter A. , Hofman Albert , Brayne Carol , Breteler Monique M. B. , Clarke Michael , Copeland John R. M. , Dartiques Jeanm‐François , Engedal Knut , Hagnell Olle , Heeren Thea J. , Jonker Cees , Lindesay James , Lobo Antonio , Mann Anthony H. , Mölsä Pekka K. , Morgan Kevin , O'Connor Daniel W. , Droux Arnaldo da Silva , Sulkava Raimo , Kay David W. K. , Amaducci Luigi ,   EURODEM‐Prevalence Research Group
Published: January 2005

AbstractWe selected, reanalyzed, and compared data from current prevalence studies of vascular dementia in Europe. Inclusion criteria were: dementia defined by the Diagnostic and Statistical Manual for Mental Disorders, edition 3, or equivalent criteria; case finding through direct individual examination; appropriate sample size; and inclusion of institutionalized persons. Mixed dementia was combined with vascular dementia. Of the 23 surveys of dementia considered, five fulfilled the inclusion criteria. Age‐specific prevalence varied more widely for men than for women; differences were greater in older ages. The prevalence increased steeply with advancing age in all countries, and was generally higher in men; it declined over 15 years in the age class of 80 to 89 years in one Swedish population. Within populations, Alzheimer's disease was generally more common than vascular dementia. Unfortunately, prevalence studies of vascular dementia are limited in Europe and worldwide, and their comparison is impeded by the lack of common diagnostic criteria.
Inter‐ and intra‐examiner reliability of nerve conduction measurements in normal subjects
Authors: Chaudhry Vinay , Cornblath David R. , Mellits E. David , Avila Orlando , Freimer Miriam L. , Glass Jonathan D. , Reim Johannes , Ronnett Gabriele V. , Quaskey Shirley A. , Kuncl Ralph W. 
Published: January 2005

AbstractNerve conduction studies are widely employed in evaluating patients with peripheral nerve disease and are often used serially to measure disease progression or to assess a therapeutic intervention. We determined the inter‐ and intra‐examiner reliability of electrophysiological data by performing serial nerve conduction studies on 7 normal subjects. A high degree of inter‐examiner reliability was present, but significant inter‐examiner differences were found. Our results suggest that if nerve conduction studies are to be used longitudinally, they should optimally be performed by a single examiner to minimize the degree of variability associated with different examiners.
Thrombotic microangiopathy isolated to the central nervous system
Authors: Dawson Ted M , Lavi Ehud , Raps Eric C. , Goldberg Herbert I. 
Published: January 2005

AbstractA man with plasma cell dyscrasia and bone marrow infiltration presented with rapidly progressive encephalopathy. Magnetic resonance imaging revealed multiple small areas of abnormal signal that correlated with the autopsy findings of thrombotic microangiopathy isolated to the central nervous system.
Outcome after ischemia in the developing sheep brain: An electroencephalographic and histological study
Authors: Williams Chris E. , Gunn Alistair J. , Mallard Carina , Gluckman Peter D. 
Published: January 2005

AbstractThe role of seizures occurring with perinatal hypoxic‐ischemic encephalopathies is unclear. We examined the relationships between the time course of parasagittal electroencephalographic (EEG) activity and pathological outcome following transient cerebral ischemia, which was induced in 33 chronically instrumented fetal sheep by occluding the carotid arteries after ligation of the vertebral‐carotid anastomoses. The EEG was quantified with real‐time spectral analysis. Histological outcome was assessed 72 hours later. After 10 or 20 minutes of ischemia, EEG activity was depressed and then progressively recovered and mild selective neuronal loss was seen. The length of this depression correlated with the duration of ischemia (r = 0.88). After 30 or 40 miniutes of ischemia, EEG activity remained depressed for 8 ± 2 hours, followed by a rapid transition to low‐frequency epileptiform activity that reached maximum intensity at 10 ± 3 hours. By 72 hours, EEG intensity had fallen below control levels. This sequence of prolonged depression, epileptiform activity, and then loss of intensity was associated with the development of laminar necrosis of the underlying cortex. These electrophysiological sequelae may have prognostic value. The results indicate that after a severe hypoxicischemic insult, the parasagittal cortex becomes hyperexcitable before the final loss of activity. Secondary neuronal death may occur in this phase.
Transplantation of fetal dopamine neurons in Parkinson's disease: One‐year clinical and neurophysiological observations in two patients with putaminal implants
Authors: Lindvall Olle , Widner Håkan , Rehncrona Stig , Brundin Patrik , Odin Per , Gustavii Björn , Frackowiak Richard , Leenders Klaus L. , Sawle Guy , Rothwell John C. , Ourklund Anders Bj , Marsden C. David 
Published: January 2005

AbstractVentral mesencephalic tissue from aborted human fetuses (age, 6–7 weeks' postconception) was implanted unilaterally into the putamen using stereotaxic surgery in 2 immunosuppressed patients (Patients 3 and 4 in our series) with advanced idiopathic Parkinson's disease. Tissue from 4 fetuses was grafted to each patient. Compared with our previous 2 patients, the following changes in the grafting procedure were introduced: the implantation instrument was thinner, more tissue was placed in the operated structure, and the time between abortion and grafting was shorter. There were no postoperative complications. Both patients showed a gradual and significant amelioration of parkinsonian symptoms (most marked in Patient 3) starting at 6 and 12 weeks after grafting, respectively, reaching maximum stability at approximately 4 to 5 months; patients remained relatively stable thereafter during the 1‐year follow‐up period. Clinical improvement was observed as a reduction of the time spent in the “off” phase and the number of daily “off” periods; a lessening of bradykinesia and rigidity during the “off” phase, mainly but not solely on the side contralateral to the graft; and a prolongation and change in the pattern of the effect of a single dose of L‐dopa. Neurophysiological measurements revealed a more rapid performance of simple and complex arm and hand movements bilaterally, but primarily contralateral to the graft. The results indicate that patients with Parkinson's disease can show significant and sustained improvement of motor function after intrastriatal implantation of fetal dopamine‐rich mesencephalic tissue. The accompanying paper by Sawle and colleagues describes the results of repeated positron emission tomography scans in these patients.
Multifocal inflammatory leukoencephalopathy with 5‐fluorouracil and levamisole
Authors: Hook C. Christopher , Kimmel David W. , Kvols Larry K. , Scheithauer Bernd W. , Forsyth Peter A. , Rubin Joseph , Moertel Charles G. , Rodriguez Moses 
Published: January 2005

AbstractA cerebral demyelinating disease developed in 3 patients during adjuvant therapy with 5‐fluorouracil and levamisole for adenocarcinoma of the colon. None of the patietns had evidence of metastatic disease or prior neurological disease. The duration of chemotherapy before onset of neurological symptoms ranged from 15 to 19 weeks. The total dose of 5‐fluorouracil was 9.7 to 15.7 gm. The total dose of levamisole was 2.7 to 3.75 gm. Two patietns presented with a subacute (2–3 weeks) progressive decline in mental status and ataxia. The third patient had two unexplained episodes of loss of consciousness. In each, magnetic resonance imaging with gadolinium demostrated prominent multifocal enhancing white matter lesions. Cerebral biopsy was performed stereotaxically in 2 patietns. The morphological features were those of active demyelinating disease. The myelin loss was associated with numerous dispersed as well as vasocentric macrophages, sparing of axons, and pervisacular lymphocytic inflammation. Electron microscopy confirmed the light microscopic findings. All 3 patients improved after cessation of chemotherapy and a short course of corticosteroid therapy. Our patients represent the first reported examples of an inflammatory leukoencephalopathy associated with the administration of 5‐fluorouracil and levamisole. This syndrome may represent the pathological basis for 5‐fluorouracil neurotoxicity, although we cannot completely exclude the role of levamisole.
Phenotypic characteristics of familial Creutzfeldt‐Jakob disease assoicated with the codon 178AsnPRNP mutation
Authors: Brown Paul , Goldfarb Lev G. , Kovanen Jussi , Haltia Mattie , Cathala Françoise , Sulima Michael , Gibbs C. J. , Gajdusek D. Carleton 
Published: January 2005

AbstractA group of 43 patietns from seven families affected by Creutzfeldt‐Jakob disease (CJD) with the codon 178Asn mutation of the PRNP amyloid precursor gene is compared to a group of 211 patients with the sporadic form of the disease. As a group, the patients with codon 178Asn mutation had an earlier age at onset of illness (almost always presenting as an insidious loss of memory), a longer duration of illness, and an absence of periodic electroencephalographic activity. Transmission of disease to primates was accomplished using brain tissue homogenates from 6 of 10 patients, resulting in significantly shorter incubation periods than those due to sporadic CJD inocula. These findings are interpreted and discussed in terms of possible differences in the temporospatial evolution of damage to the brain, and of accelerated induction of polymerized amyloid protein by its mutationally altered template precursor.