bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated treatment with chimeric anti‐CD4 antibody in multiple sclerosis
Authors: Lindsey R. J. W. , Hodgkinson S. , Mehta R. , Mitchell D. , Enzmann D. , Steinman L. 
Published: January 2005

AbstractWe treated 21 multiple sclerosis patients with two to four doses of cM‐T412, a chimeric monoclonal antibody against the CD4 antigen found on helper/inducer T lymphocytes. The mean number (± standard error) of circulating CD4 lymphocytes decreased from 888 (± 81) cells/mm3 at baseline to 246 (± 18) after treatment. At 1 year after the last treatment, the CD4 count had recovered to only 335 (± 32). The antibody had no effect on CD8 lymphocytes, B lymphocytes, or other leukocytes. Side effects were minimal. Despite the prolonged depletion of CD4 lymphocytes, no opportunistic infections occurred. Only 1 patient had a possible allergic reaction. Most patients were clinically stable, but a few progressed. We conclude that repeated treatment with cM‐T412 is effective in reducing the number of circulating CD4 lymphocytes and has no limiting side effects.
Decreased levels of soluble amyloid β‐protein precursor are associated with Alzheimer's disease in concordant and discordant monozygous twin pairs
Authors: Wagner Steven L. , Peskind Elaine R. , Nochlin David , Provow Sally , Farrow Jeffrey S. , Pandian M. R. , Cleveland Michelle , Ito Ralph K. , Farlow Martin R. 
Published: January 2005

AbstractWe conducted immunochemical measurements of soluble amyloid β‐protein precursor (βPP) in cerebrospinal fluid (CSF) from three monozygous twin pairs. Two of the twin pairs are discordant for Alzheimer's disease and one pair showed concordance for Alzheimer's disease, which was confirmed neuropathologically. All affected individuals displayed substantially lower levels of soluble βPP in CSF compared with the unaffected individuals. There were no differences in total protein levels in CSF samples from the affected twins compared with those of the unaffected twins. These studies suggest that decreased soluble βPP in CSF may reflect neuropathological processes in Alzheimer's disease involving βPP.
The Denny‐brown collection: A research and teaching resource
Authors: Vilensky Joel A. , Gilman Sid , Dec Elaine M. 
Published: January 2005

AbstractA large collection of potentially valuable materials compiled by the late Dr Derek Denny‐Brown is described. This consists of 2,200 films of monkeys with central nervous system lesions, associated behavior and neuropathological descriptions, and histological slides. There are also 500 films of patients with a wide assortment of diseases, including some not currently seen, like postencephalitic parkinsonism. This description will enable contemporary researchers to utilize this collection in their research and teaching programs.
Frequency and clinical correlates of anti–neural IgM antibodies in neuropathy associated with IgM monoclonal gammopathy
Authors: Nobile‐Orazio E. , Manfredini E. , Carpo M. , Meucci N. , Monaco S. , Ferrari S. , Bonetti B. , Cavaletti G. , Gemignani F. , Durelli L. , Barbieri S. , Allaria S. , Sgarzi M. , Scarlato G. 
Published: January 2005

AbstractWe studied the frequency and clinical correlates of different IgM specificities in 75 patients with neuropathy associated with IgM monoclonal gammopathy. Patients were tested for IgM reactivity with the myelin‐associated glycoprotein, PO, neurofilaments, and tubulin by immunoblot; with GM1, asialo‐GM1, GM2, GD1a, GD1b, sulfatide, and chondroitin sulfate C by enzyme‐linked immunosorbent assay; and with brain and nerve glycolipids by overlay highperformance thin‐layer chromatography. Forty‐two patients (56%) had high titers of IgM antibodies to MAG; 4 (5%), to sulfatide (1 also to myelin‐associated glycoprotein); 4 (5%), to the 200‐kd neurofilament (2 also to myelin‐associated protein); and 1 each, to GD1b and chondroitin sulfate C. No reactivity was found in 26 patients (35%). More patients with anti–myelin‐associated glycoprotein IgM (62%) than with unknown IgM reactivity (31%) had a predominantly sensory neuropathy (p < 0.025). Nerve conduction findings were consistent with a demyelinating neuropathy in 77% of patients reactive to myelin‐associated glycoprotein and 24% with unknown reactivity (p < 0.0001) and the mean conduction velocity of peroneal nerve was lower in the former group (22.9 m/sec) than in the latter group (39.6 m/sec) (p < 0.000001). Patients with anti–sulfatide IgM had a sensorimotor neuropathy with morphological evidence of demyelination while anti–neurofilament IgM was not associated with homogeneous findings. Patients with anti–GD1b or anti–chondroitin sulfate C IgM had a predominantly motor impairment. The frequent occurrence of anti–neural IgM antibodies in neuropathy associated with IgM gammopathy, and their frequent, though not constant association with similar neuropathy features, support their possible pathogenetic role in the neuropathy.
Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA
Authors: Liu Philip K. , Salminen Antero , He Ye Y. , Jiang Ming H. , Xue J. J. , Liu Jia S. , Hsu Chung Y. 
Published: January 2005

AbstractActivation of c‐fos, an immediate early gene, and the subsequent expression of the Fos protein have been noted following focal cerebral ischemia. Fos and Jun form a heterodimer as activator protein 1 (AP‐1), which transregulates the expression of several genes. To study the postischemic events related to c‐fos expression, we suppressed the expression of c‐fos by intraventricular infusion of an antisense oligodeoxynucleotide (anti‐rncfosr115) of c‐fos mRNA. The effectiveness of anti‐rncfosr 115 was confirmed first by its capability to block in vitro c‐fos mRNA translation. In vivo, after intraventricular infusion of 32P‐labeled anti‐rncfosr115, the oligodeoxynucleotide was internalized iwthin 6 hours and detectable aslo in the nucleic acids fraction up to 41 hours. Treatment of the recovered nucleic acids with RNase H separated the labeled oligodeoxynucleotide from the nucleic acid fraction, indicating an association of the antisense oligodeoxynucleotide and cellular RNA after uptake. When focal cerebral ischemia was induced 16 hours after the infusion of anti‐rncfosr115, the postischemic increase in Fos expression and AP‐1 binding activity were suppressed. Specificity of the effect of anti‐rncfosr 115 was suggested by its failure to suppress the DNA binding activity of nuclear cyclic AMP response elements. These results support the hypothesis that increased AP‐1 binding activity following focal cerbral ischemia is dependent on Fos expression and can be inhibited in vivo by antisense c‐fos oligodeoxy‐nucleotides.
Selective vulnerability in Huntington's disease: Preferential loss of cannabinoid receptors in lateral globus pallidus
Authors: Richfield Eric K. , Herkenham Miles 
Published: January 2005

AbstractSelective neuronal vulnerability is a key feature of the neuropathology of Huntington's disease. We used [3H]CP‐55,940, a synthetic cannabinoid, to label cannabinoid receptors in tissue sections from individuals dying with Huntington's disease and from normal control subjects. The density of cannabinoid receptors in striatum and pallidum was measured using quantitative autoradiography. There was a greater loss of cannabinoid receptors on striatal nerve terminals in the lateral pallidum compared to the medial pallidum, in Huntington's disease of all neuropathological grades. The disparity in binding density between the lateral and medial pallidum increased with higher grades of disease. There was also a greater loss of receptors in the lateral pallidum than in the putamen. The disproportionate loss of receptors in the lateral pallidum compared to the putamen increased in magnitude with severity of neuropathological grade. These data support the relative preferential loss or dysfunction of striatal neurons projecting to the lateral pallidum compared to neurons projecting to the medical pallidum. Terminals in the lateral pallidum containing cannabinoid receptors may be affected earlier or more severely than terminals in the medial pallidum, and both pallidal segments may be affected before or more severely than cell bodies or dendrites in the striatum. Terminal loss of markers may represent a response to perikaryal injury or dysfunction, or less likely, may indicate the primary site of neuronal damage in Huntington's disease.
Autoantibodies to glutamic acid decarboxylase in palatal myoclonus and epilepsy
Authors: Nemni R. , Braghi S. , Natali‐Sora M. G. , Lampasona V. , Bonifacio E. , Comi G. , Canal N. 
Published: January 2005

AbstractWe report the presence of serum autoantibodies directed aginst glutamic acid decarboxylase in a patient with epilepsy and palatal myoclonus not associated with brain lesions. Glutamic acid decarboxylase antibody reactivity was dependent on the presence of carboxy‐terminal amino acids, similar to that reported in patients with stiff‐man syndrome. Marked reduction in the frequency of epileptic attacks and improvement in palatal myoclonus occurred when benzodiazepine was administered and phenytoin was gradually tapered. Testing for antiglutamic acid decarboxylase antibodies may be indicated in patients with palatal myoclonus and with convulsive disorders refractory to therapy.
Herpes simplex virus genomes in human nervous system tissue analyzed by polymerase chain reaction
Authors: Baringer J. Richard , Pisani Pamela 
Published: January 2005

AbstractHerpes simplex virus (HSV) is known to establish latency in human trigeminal ganglia. It has been speculated that the virus might also be present in latent fashion in normal human brain, where it might be responsible for conditions such as herpes simplex encephalitis, and less plausibly as a cause for multiple sclerosis or Alzheimer's disease. To test the possibility that HSV exists in normal human brain, we utilized the polymerase chain reaction to assess the frequency and distribution of HSV genomes in the nervous system tissues of patients dying of nonneurological causes. Nine samples were obtained in a systematic fashion from olfatory bulb, gyrus rectus, hippocampus amygdala, calcarine cortex, pons, medulla, cerebellum, and trigeminal ganglia from each of 40 individuals dying of nonneurological disease. HSV genomes were sought in each sample using primers from four regions of the HSV genome. The primers identified in 26 (65%) of 40 samples of trigeminal ganglia. From 30 patients seropositive to HSV, sequences were amplified from 23 (77%). HSV genomic sequences could be amplified and detected in 14 (35%) of 40 brains. The positive areas included medulla, olfactory bulbs, pons, gyrus rectus, amygdala, and hippocampus. The study has confirmed the previous demonstration of latent HSV in trigeminal ganglia in normal humans. The frequency of latent HSV in trigeminal ganglia is in general agreement with results obtained by explanation of ganglia. In addition HSV sequences could be amplified from a variety of other central nervous system structures, suggesting the presence of the virus in latent state in normal central nervous system. Wheter the virus is important in the pathogenesis of nervous system diseases is not answered by these studies. However, it appears that the virus, commonly latent in trigeminal ganglia, may be detectable with lesser frequency in normal brain.
Hippocampal neuronal loss and regional hypometabolism in temporal lobe epilepsy
Authors: Henry Thomas R. , Babb Thomas L. , Engel Jerome , Mazziotta John C. , Phelps Michael E. , Crandall Paul H. 
Published: January 2005

AbstractThe pathophysiology of widespread interictal hypometabolism in temporal lobe epilepsy is unknown but might reflect neuronal loss and diaschisis. We found no significant correlation between any cortical region's metabolism on preoperative {18F} fluorodeoxyglucose positron emission tomography and neuronal density of resected hippocampi in 40 patients. We conclude that hippocampal neuronal loss and diaschisis cannot account for the regional interictal hypometabolism of temporal lobe epilepsy.
Myopathy and paraproteinemia with serum igm binding to a high‐ molecular‐weight muscle fiber surface protein
Authors: Al‐Lozi M. T. , Pestronk A. , Yee W. C. , Flaris N. 
Published: January 2005

AbstractWe evaluated a 69‐year‐old man with Waldenström's macroglobulinemia (IgM‐κ M‐protein) and progressive weakness over 2 to 3 years. The neurological examination showed symmetrical, predominantly proximal weakness. Electrophysiological testing revealed small brief motor unit potentials with fibrillations and positive sharp waves consistent with an irritative myopathy. The muscle biopsy specimen showed myopathic changes including variation in fiber size and increased connective tissue but no inflammation. IgM‐κ but not IgM‐λ was deposited along the surface of muscle fiber membranes. Serum IgM‐κ but not IgM‐λ from the patient stained the surface of normal human muscle fibers but not other regions of muscle fibers or other tissues. The serum IgM‐κ at dilutions up to 1: 512,000 bound to a high‐molecular‐weight muscle protein by Western and dot blot studies. By enzyme‐linked immunosorbent assay and Western blot analysis, serum IgM‐κ bound specifically to the muscle protein and not to other muscle or neural antigens, including GM1 ganglioside, myelin‐associated glycoprotein, and sulfatide. We conclude that the myopathy in our patient is probably related to the presence of serum IgM‐κ antibodies directed against a muscle surface antigen. Characterization of the target antigen, a high‐molecular‐weight protein located specifically in muscle, should further elucidate the pathogenesis of this presumably humorally mediated immune myopathy.
The CYP2D6B mutant allele is overrepresented in the Lewy body variant of Alzheimer's disease
Authors: Saitoh T. , Xia Y. , Chen X. , Masliah E. , Galasko D. , Shults C. , Thal L. J. , Hansen L. A. , Katzman R. 
Published: January 2005

AbstractApproximately one‐fourth of neuropathologically confirmed cases of Alzheimer's disease (AD) also have brainstem and neocortical Lewy bodies, constituting a Lewy body variant of AD. Because Lewy bodies are a pathologic hallmark of Parkinson's disease (PD), this subpopulation of AD subjects may have the same risk factors as PD subjects. Analyses of the cytochrome P450 CYP2D6‐debrisoquine 4‐hydroxylase mutant B allele, a susceptibility gene for PD, revealed a higher representation of this allele in the Lewy body variant of AD than in pure AD or non‐AD without Lewy bodies.
Drenching sweats as an off phenomenon in parkinson's disease: Treatment and relation to plasma levodopa profile
Authors: Sage Jacob I. , Mark Margery H. 
Published: January 2005

AbstractWe followed 4 patients with Parkinson's disease and severe, intermittent, drenching sweats. One patient was studied with serial plasma levodopa levels and simultaneous clinical examinations. She was observed during a severe sweating episode; this was associated with subtherapeutic plasma levodopa levels (low dopa state). All 4 patients' sweats responded favourably to the institution of agonist therapy. Drenching sweats should be considered part of the spectrum of off‐period levodopa‐related fluctuations in Parkinson's disease.
Staggering gait in medical history
Authors: Schiller Francis 
Published: January 2005

AbstractDrunkenness and senility were recognized early as the basis of a staggering gait. To these were added venereal excesses, hence syphilis. Medical and scientific concerns began to be focused on “locomotor ataxia” in the 19th century with the systematic development of neuroanatomy and physiology. Rolando and Flourens were followed by Romberg and Todd, and later Friedreich, who all gave the spinal cord temporal precedence as a culprit over the cerebellum–and there were some forerunners. New spinal sensory pathways were delineated by Goll, Flechsig, and Gowers. In France, we must specially credit Duchenne as well as Bouillaud, and later Babinski, Marie, and Dejerine, for correcting, differentaiting, extending, and underpinning current concepts. Failures of input and output, of conduction and central coordination were invoked and explained, among them the vestibular apparatus, as well as the causation by neoplasms, demyelination, degeneration, and infarction affecting even the frontal lobe, thalamus, and basal ganglia Clinical testing was brought up to 20th‐century standards essentially by Sherrington and Bárány, followed by Dandy, the neurosurgeon who showed how to replace ventricular fluid by air, more recently made obsolete by modern roentgenographic procedures. And tabes dorsalis, once the chief culprit, has practically become a medical anachronism thanks to penicillin.
Acute human stroke studied by whole brain echo planar diffusion‐weighted magnetic resonance imaging
Authors: Warach Steven , Gaa Jochen , Siewert Bettina , Wielopolski Piotr , Edelman Robert R. 
Published: January 2005

AbstractOur purpose was to use whole brain echo planar magnetic resonance imaging (MRI) to identify and characterize diffusion abnormalities in acute cerebral ischemia. We studied 40 patients as early as 3 hours after onset of signs and symptoms of cerebral ischemia. Diffusion‐weighted imaging (DWI) of the entire brain could be completed in 3 seconds or, using seven different diffusion sensitivities (maximum b=1,271 sec/2), in 48 seconds. Measurements and synthetic maps were made of apparent diffusion coefficients (ADC), a physiological parameter that characterizes the self‐diffusion of water in tissue. Early ischemic lesions were identified with DWI as hyperintense regions of decreased ADC in all patients who subsequently developed infarction, before changes were evident on conventional MRI in cases studied earlier than 6 hours after onset of ischemic symptoms. Lesions as small as 4 mm in diameter were identified. The extent of lesions within white matter was best defined by controlling for the anisotropic effect of axonal orientation. The mean ADC (± SD) for control regions in the 36 patients was 9.15 (± 2.91) × 10−4 mm2/sec. Mean ADC of ischemic regions was 56% of control values at 6 hours or less and stayed significantly reduced for 3 to 4 days after onset of ischemia. The relative ADC increased progressively over time to be pseudonormalized at 5 to 10 days and elevated in the chronic state, making the distinction of acute lesions adjacent to chronic infarcts readily apparent. DWI with echo planar imaging measures a unique physiological parameter that is sensitive to ischemic changes before conventional MRI. Its potential role in the quantitative study of human stroke pathophysiology and therapeutics is the subject of further investigation.
Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in down Syndrome
Authors: Iwatsubo Takeshi , Mann David M. A. , Odaka Asano , Suzuki Nobuhiro , Ihara Yasuo 
Published: January 2005

AbstractThe chronological relationship regarding deposition of amyloid β protein (Aβ) species, Aβ40 and Aβ42(43), was investigated in 16 brains from Down syndrome patients aged 31 to 64 years. The frontal cortex was probed with two end‐specific monoclonals that recognize Aβ40 or Aβ42(43). All senile plaques detected with an authentic β monoclonal were also Aβ42(43) positive, but only a varying proportion was Aβ40 positive. In young (≤ 50 years old) brains there were many Aβ42(43)‐positive, Aβ40‐negative diffuse plaques, but only few Aβ40‐positive senile plaques (mean, 6.3% of total number of senile plaques). The 2 youngest Down syndrome brains showed only diffuse plaques that were all Aβ42(43) positive but Aβ40 negative. Old (≤ 50 years old) brains contained many mature senile plaques with amyloid cores in addition to diffuse and immature plaques and the proportion of Aβ40‐positive senile plaques was increased (mean, 42% of total). Cerebral amyloid angiopathy was more abundant in old Down syndrome brains and was positive for both Aβ40 and Aβ42(43). In cerebral amyloid angiopathy, Aβ40 predominated over Aβ42(43) in both staining intensity and number of positive vessels. These results indicate that (1) the Aβ species intially deposited in the brain as senile plaques is Aβ42(43) and Aβ40 only appears a decade later, and (2) in cerebral amyloid angiopathy Aβ40 appears as early as Aβ42(43).
Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia
Authors: Ceballos‐Baumann A. O. , Passingham R. E. , Warner T. , Playford E. D. , Marsden C. D. , Brooks D. J. 
Published: January 2005

AbstractRegional cerebral blood flow was measured using H215O and positron emission tomography in a group of 6 patients with idiopathic torsion dystonia and in a group of 6 control subjects. Subjects were scanned while at rest and when performing paced joystick movements in freely chosen directions with the right hand. Patients with idiopathic torsion dystonia showed significant overactivity in the contralateral lateral premotor cortex, rostral supplementary motor area, Brodmann area 8, anterior cingulate area 32, ipsilateral dorsolateral prefrontal cortex, and bilateral lentiform nucleus. Significant underactivity was found in the caudal supplementary motor area, bilateral sensorimotor cortex, posterior cingulate, and mesial parietal cortex. These results are consistent with inappropriate overactivity of striatofrontal projections and impaired activity of motor executive areas in idiopathic torsion dystonia and may explain the simultaneous dystonic posturing and bradykinesia evident in these patients.
In vitro evidence for a dual role of tumor necrosis factor‐α in human immunodeficiency virus type 1 encephalopathy
Authors: Wilt Susan G. , Milward Elizabeth , Zhou Jia Min , Nagasato Kunihiko , Patton Heather , Rusten Ray , Griffin Diane E. , O'Connor Michael , Dubois‐Dalcq Monique 
Published: January 2005

AbstractMicroglial cell activation, myelin alteration, and abundant tumor necrosis factor (TNF)‐α message have been observed in the brains of some human immunodeficiency virus type 1 (HIV ‐ 1)vinfected and demented patients. We therefore used cultures of purified human microglia and oligodendrocytes derived from adult human brain to examine the role of TNF‐α in HIV‐1 encephalopathy. Human microglia synthesize TNF‐α message and protein in vitro. When these cells were infected with HIV‐1 JrFL and maintained in the presence of TNF‐α antibodies, soluble TNF‐α receptors, or the TNF‐α inhibitor pentoxifylline, viral replication was delayed or strongly inhibited. Both human microglia and oligodendrocytes express the two TNF receptors, TNF‐Rl, which has been implicated in cytotoxicity, and TNF‐R2. While TNF‐α may enhance HIV‐1 replication in an autocrine manner, it is not toxic for microglia. In contrast, recombinant human TNF‐α causes oligodendrocyte death in a dose‐dependent manner. In situ detection of DNA fragmentation in some cells indicated that oligodendrocyte death may occur by apoptosis. Addition of live microglia or medium conditioned by these cells also resulted in 30 to 40% oligodendrocyte death, which was largely prevented by TNF‐α inhibitors. We propose that TNF‐α plays a dual role in HIV‐1 encephalopathy, enhancing viral replication by activated microglia and damaging oligodendrocytes. Thus, TNF‐α inhibitors may alleviate some ofthe neurological manifestations of acquired immunodeficiency syndrome.