bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoantibodies against the Hel‐N1 RNA‐binding protein among patients with lung carcinoma: An association with type I anti–neuronal nuclear antibodies
Authors: Dropcho Edward J. , King Peter H. 
Published: January 2005

AbstractHel‐N1 is a novel human complementary DNA encoding a neuronal RNA‐binding protein which shares considerable sequence homology with the HuD protein, a target of type I anti–neuronal nuclear antibodies in patients with paraneoplastic encephalomyelitis. The aim of the present study was to determine the prevalence of antibodies against the Hel‐N1 protein among patients with lung carcinoma, including those with paraneoplastic disorders. Sera from 45 patients with lung cancer (42 with small‐cell carcinoma) and from 28 control patients with other neurological diseases were studied by enzyme‐linked immunosorbent assay (ELISA) and by immunoblotting with recombinant Hel‐N1 protein. Sixteen of the 45 lung cancer patients (14 with small‐cell and 2 with undifferentiated carcinoma) had paraneoplastic encephalomyelitis and high‐titer type I anti–neuronal nuclear antibodies; sera from each of these 16 patients also showed strong reactivity with Hel‐N1 protein. The other 29 lung cancer patients, all of whom had neurological dysfunction and 24 of whom had known or suspected paraneoplastic disorders, lacked the type I antibody by standard testing. The mean anti–Hel‐N1 titer (by ELISA) of sera from patients negative for type I anti–neuronal nuclear antibody was significantly less than that of the patients positive for the type I antibody, but exceeded that of the control patients with other neurological diseases (p < 0.001). Fifteen (52%) of the 29 type I antibody–negative patients had positive serum anti–Hel‐N1 titers which did not overlap the high anti–Hel‐N1 titers of the 16 type I antibody–positive patients. These findings support the theory that type I anti–neuronal nuclear antibodies react with a family of neuronal RNA‐binding proteins, and suggest that these proteins share one or more epitopes. High titers of circulating anti–Hel‐N1 antibodies correlate with paraneoplastic encephalomyelitis, while lower anti–Hel‐N1 titers are present in a sizeable proportion of patients with small‐cell lung cancer without a clear association with their clinical condition.
Glutathione‐related enzymes in brain in Parkinson's disease
Authors: Sian J. , Dexter D. T. , Lees A. J. , Daniel S. , Jenner P. , Marsden C. D. 
Published: January 2005

AbstractThe activities of enzymes related to glutathione synthesis, degradation, and function were analyzed in various brain regions (cerebral cortex, caudate nucleus, putamen, globus pallidus, and substantia nigra) from patients dying with pathologically proven Parkinson's disease (PD) and multiple system atrophy (MSA), and from matched controls with no neurological disorder. The activity of the glutathione degradative enzyme, σ‐Glutamyltranspeptidase, was selectively elevated in substantia nigra (SN) in PD. In contrast, the activity of the synthetic enzyme, σ‐glutamylcysteine synthetase, was unaltered in SN and other brain areas in PD. Similarly, glutathione peroxidase and glutathione transferase activities were unaltered in SN or in other brain regions in PD. σ‐Glutamylcysteine synthetase, σ‐glutamyltranspeptidase, glutathione peroxidase, and glutathione transferase activities were normal in SN and most other brain areas in MSA. However, glutathione peroxidase activity was increased in the lateral globus pallidus and caudate nucleus in MSA. The depletion of reduced glutathione (GSH) in the SN in PD, with no change in oxidized glutathione (GSSG), may be due to efflux of GSH mainly out of glia promoted by σ‐glutamyltranspeptidase, perhaps with additional increased conversion of GSH to GSSG (which itself is transported out of cells by σ‐glutamyltranspeptidase), in response to increased hydrogen peroxide formation.
Increased transforming growth factor‐β, interleukin‐4, and interferon‐γ in multiple sclerosis
Authors: Link Joanne , Söderström Mats , Olsson Tomas , Höjeberg Bo , Ljungdahl Årke , Link Hans 
Published: January 2005

AbstractThe inflammatory nature of multiple sclerosis (MS) implicates the participation of immunoregulatory cytokines, including the T‐helper type 1 (Th1) cell–associated interferon‐σ (IFN‐σ), the Th2 cell–related interleukin‐4 (IL‐4), and the immune response–downregulating cytokine transforming growth factor‐β (TGF‐β), but proof for their involvement in MS has been lacking. By adopting in situ hybridization with complementary DNA oligonucleotide probes for human IFN‐ IL‐4, and TGF‐β, the expression of mRNA for these cytokines was detected in mononuclear cells (MNC) from blood and cerebrospinal fluids. Strongly elevated levels of MNC expressing all three cytokines were found in peripheral blood and at even higher frequencies in cerebrospinal fluid from untreated patients with MS and optic neuritis, i.e., a common first manifestation of MS, compared with patients with other neurological diseases and healthy subjects. In MS and optic neuritis, IL‐4 mRNA expressing cells predominated, followed by TGF‐β– and IFN‐σ–positive cells. Control patients with myasthenia gravis had similarly elevated levels of IFN‐σ and TGF‐β mRNA expressing blood MNC but lower numbers of IL‐4–positive cells. No or slight disability of MS was associated with high levels of TGF‐β mRNA expressing cells, while MS patients with moderate or severe disability had high levels of IFN‐σ–positive cells. IFN‐σ and TGF‐β may have opposing effects in MS, and treatments inhibiting IFN‐σ and/or promoting TGF‐β might ameliorate MS.
Decreased cerebrospinal fluid levels of β‐endorphin in Japanese patients with Joseph disease
Authors: Matsuishi Toyojiro , Sakai Tetsuo , Nagamitsu Shinichiro , Komori Hironori , Iwashita Hiroshi , Kato Hiroshisa 
Published: January 2005

AbstractWe measured the cerebrospinal fluid (CSF) levels of β‐endorphin in 7 Japanese patients with Joseph disease and compared them with control values. The 7 patients included 4 with type I and 3 with type II disease; their mean age was 45.7 ± 12.09 years. Diseased controls were matched in age to the patients studied. In these patients, CSF β‐endorphin level was significantly lower than in the controls (40% of normal values). An alteration in CSF β‐endorphin level may explain some of the neurological impairment found in Joseph disease.
Multislice proton magnetic resonance spectroscopic imaging in X‐linked adrenoleukodystrophy
Authors: Kruse Bernd , Barker Peter B. , van Zijl Peter C. M. , Duyn Jeff H. , Moonen Chrit T. W. , Moser Hugo W. 
Published: January 2005

AbstractMultislice proton magnetic resonance spectroscopic imaging permits metabolic analysis of brain tissue in vivo by data acquisition in four oblique axial slices, each 15‐mm thick and divided into 0.8‐ml single‐volume elements. We applied this technique to the systematic study of 25 patients with adrenoleukodystrophy: 3 with the severe childhood or adult cerebral form of the disease, 5 with adrenomyeloneuropathy, 12 with no demonstrable neurological involvement, and 5 women heterozygous for adrenoleukodystrophy who had some degree of neurological disability. Abnormalities on magnetic resonance spectroscopic imaging included a reduction in N‐acetyl aspartate, an increase in cholin‐containing compounds, and at times, an increase in lactate. Five patients showed abnormalities in the presence of normal‐appearing magnetic resonance images, and in 8 other patients the alterations on spectroscopic images were more severe than those demonstrable by magnetic resonance imaging. Correlation with clinical course suggests that an increase in the choline‐containing compounds is associated with an active demyelinative process, whereas such compounds are not elevated in lesions that are stable. We conclude that magnetic resonance spectroscopic imaging is a more sensitive indicator of early neurological involvement thatn is magnetic resonance imaging, and that the character of abnormalities detected by the former technique may serve as a gauge of the degree of activity of the demyelinating process and as a guide to the selection and evaluation of therapeutic approaches.
Neurological complications of peripheral and cutaneous T‐cell lymphomas
Authors: Kaufman David K. , Habermann Thomas M. , Kurtin Paul J. , O'Neill B. P. 
Published: January 2005

AbstractTo determine the frequency and pattern of neurological complications of T‐cell lymphoma (TCL), we retrospectively reviewed the medical records of 316 patients with TCL diagnosed between January 1984 and May 1991. Disease entities not included in this study were lymphoblastic lymphoma, primary central nervous system lymphoma, CD30‐positive anaplastic large cell lymphoma, and lymphomas secondary to human immunodeficiency virus or human T‐cell lymphotropic virus type I. Cases were classified as having direct complications (parenchymal, leptomeningeal, epidural, or peripheral) or indirect complications (paraneoplastic, disease related, or treatment related). Preexisting neurological conditions were excluded. The overall rate of neurological complications was 7.9%. The frequency of neurological complications in peripheral TCL and cutaneous TCL was 17% and 3%, respectively, with at least half of the neurological complications in both conditions due to direct involvement of the nervous system. Direct neurological complications of TCL were primarily due to leptomeningeal and parenchymal involvement. There were no cases of epidural spinal cord disease.
Increased risk of Parkinson's disease in parents and siblings of patients
Authors: Payami Haydeh , Larsen Kimberly , Bernard Steven , Nutt John 
Published: January 2005

AbstractWe studied the incidence of Parkinson's disease in 586 first‐degree relatives (parents and siblings) of 114 randomly ascertained white patients with idiopathic Parkinson's disease and in 522 first‐degree relatives of 114 age‐matched unrelated white control subjects. Sixteen percent of patients had a family history as compared to 4% of control subjects (p < 0.01). The age‐specific cumulative incidence was higher in the first‐degree relatives of patients than in the first‐degree relatives of control subjects (p = 0.007). The age‐adjusted odds ratio was 3.5 (95% confidence interval: 1.3–9.4; p = 0.014). These results suggest that genes contribute to the etiology of Parkinson's disease.
Human immunodeficiency virus encephalitis is the pathological correlate of dementia in acquired immunodeficiency syndrome
Authors: Wiley Clayton A. , Achim Cristian 
Published: January 2005

AbstractWhile dementia has been observed in approximately one‐fourth of terminally ill patients with acquired immunodeficiency syndrome, it has been difficult to attribute this clinical disorder to a single neuropathological substrate. We used a simple and readily reproducible scale for estimating the burden of human immunodeficiency virus (HIV) in the central nervous system (i.e., severity of HIV encephalitis) and compared this to autopsy neurological summaries of dementia. Like others, we found that multinucleated giant cells were present in only half of the dementia patients. However, all of the dementia patients had severe HIV encephalitis as assessed by measurements of intra–central nervous system viral burden. Additional patients had severe HIV encephalitis without clinical histories of dementia. We interpret these latter findings as evidence that HIV encephalitis exists for a period of time before the clinical symptomatology develops. Comparison of presence or absence of concurrent cytomegalovirus encephalitis showed no association with dementia.
Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism
Authors: Vingerhoets F. J. G. , Snow B. J. , Lee C. S. , Schulzer M. , Mak E. , Calne D. B. 
Published: January 2005

AbstractPrevious estimates of the rate of progression of the nigral pathology underlying idiopathic parkinsonism (IP) have been derived mainly from pathological studies that have an inherent selection bias. Fluorodopa positron emission tomography (PET) is a reliable tool for assessing nigrostriatal dopaminergic function in vivo. We performed fluorodopa PET on two occasions, 7 years apart, on 16 patients with IP (age at the time of the first scan, 51 ± 14 yr [mean ± SD]) and 10 normal controls (age, 54 ± 16 yr). For the patients with IP, the average duration of symptoms from the time of diagnosis to the first scan was 4.5 years (range, 1–12 yr); their PET index (striatal – occipital)/occipital ratio, dropped by 1.7% per year, from 0.49 ± 0.08 to 0.43 ± 0.08 (p < 0.001). The normals' ratio decreased by 0.3% per year from 0.77 ± 0.05 to 0.75 ± 0.10 (p = 0.33). The ratios in the IP group progressed significantly faster than the controls (p = 0.036). The rate of decline in IP represents 7.8% per decade, expressed as a fraction of the normals' initial mean value at 54 years of age. These results also permit power analysis for the design of future studies assessing the effect of treatment on the underlying pathology in IP.
An oxidative defect in metabolic myopathies: Diagnosis by noninvasive tissue oximetry
Authors: Bank William , Chance Britton 
Published: January 2005

AbstractMetabolic myopathies due to a variety of enzymatic deficiencies are well recognized. The dynamics of oxygen delivery and utilization during exercise have not been observed previously in these disorders. We used a noninvasive optical technique to measure oxygen consumption in the exercising limb in normal subjects and patients with metabolic myopathies. We measured near‐infrared spectra of hemoglobin in the gastrocnemius muscle during treadmill exercise in 10 normal subjects, 1 patient with cytochromecoxidase deficiency, 2 patients with myophosphorylase deficiency, 3 patients with phosphofructokinase deficiency, and 2 patients with carnitine palmityl transferase deficiency. All normal subjects demonstrated a sustained deoxygenation during exercise, indicating an efficient utilization of delivered oxygen. The patient with cytochromecoxidase deficiency demonstrated consistent oxygenation during exercise, indicating an underutilization of delivered oxygen. In the patients with myophosphorylase or phosphofructokinase deficiency, abnormal oxgenation during exercise indicated an oxidative defect due to a lack of pyruvate production. In the patients with myophosphorylase deficiency, changes in oxidation coincident with glucose utilization and “the second wind phenomenon” were observed. Patients with carnitine palmityl transferase deficiency demonstrated a normal deoxygenation during exercise. Noninvasive tissue oximetry during exercise demonstrates specific abnormalities in a variety of metabolic myopathies, indicating abnormal oxygen utilization, and will be a useful addition to the clinical investigation of exercise intolerance.
Evidence for hypoxia‐induced, programmed cell death of cultured neurons
Authors: Rosenbaum Daniel M. , Michaelson Marc , Batter David K. , Doshi Pooja , Kessler John A. 
Published: January 2005

AbstractApoptosis, a form of cell death (“programmed” cell death) in which the nucleus and cytoplasm shrink and often fragment, serves to eliminate excessive or unwanted cells during remodeling of embryonic tissues, during organ involution, and in tumor regression. In acute pathological states, such as ischemia, the cells tend to swell and lyse—a process called necrosis. We hypothesize that the delayed neural death clinically associated with hypoxia may, in part, represent apoptosis. A tissue culture model of 24 hours of hypoxia was employed using sympathetic neurons. Pretreatment with an endonuclease inhibitor (aurintricarboxylic acid) decreased cell death by 53%, depolarizing conditions (55 mM potassium chloride) decreased cell death by 33%, and an RNA synthesis inhibitor (actinomycin D) by 26% (all have been shown to prevent apoptosis). Pretreatment with antisense c‐myc had no effect. Fluorescent staining with propidium iodide (a DNA marker) demonstrated chromatin condensation and agarose gel electrophoresis demonstrated a DNA “ladder.” These data suggest that apoptosis may play a role in hypoxic cell death and that in this paradigm, expression of c‐myc is unnecessary. This would suggest a new approach to our understanding of hypoxia and open new strategies to lessen neuronal damage secondary to this process.
Neuropathologic correlates of persistent neurologic deficit in lithium intoxication
Authors: Schneider Julie A. , Mirra Suzanne S. 
Published: January 2005

AbstractWhile acute neurological symptoms complicating lithium therapy are well recognized, persistent neurologic dysfunction is uncommon. Regardless of the duration of symptoms, neuropathological correlates of lithium toxicity are few. We report the case of a 67‐year‐old man who developed lithium toxicity manifested by encephalopathy and coma followed by persistent dysarthria and ataxia. Autopsy revealed neuronal loss and gliosis in the cerebellar cortex and dentate nuclei; the cerebellar white matter exhibited prominent spongy change. Persistent cerebellar syndrome may occur with lithium intoxication and should be considered in the differential diagnosis of chronic cerebellar dysfunction.
Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients
Authors: Rozniecki J. J. , Hauser S. L. , Stein M. , Lincoln R. , Theoharides T. C. 
Published: January 2005

AbstractMultiple sclerosis (MS) lesions are associated with infiltration of T lymphocytes and macrophages that appear to mediate myelin destruction and gliosis (scarring). Mast cells are located perivascularly in the brain, are juxtaposed to neurons, and have been shown to secrete vasoactive and inflammatory mediators in response to neuropeptides and direct nerve stimulation. Mast cells have been previously identified in MS lesions, are activated by myelin basic protein, and can participate in the regulation of blood–brain barrier permeability, as well as in myelin destruction. Here, cerebrospinal fluid from MS patients and controls with other neurologic diseases was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase. Histamine and methylhistamine were not elevated in MS. However, the mast cell specific proteolytic enzyme tryptase was significantly elevated in MS, suggesting that mast cell activation may be involved in the pathophysiology of this disease.
Tumor necrosis factor‐α messenger RNA expression in patients with relapsing‐remitting multiple sclerosis is associated with disease activity
Authors: Rieckmann P. , Albrecht M. , Kitze B. , Weber T. , Tumani H. , Broocks A. , Lüer W. , Helwig A. , Poser S. 
Published: January 2005

AbstractWe determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 29 patients with relapsing‐remitting multiple sclerosis every 4 weeks over a period of 12 months. During this period 27 relapses occurred in 14 patients (48%). Progression of disease activity as assessed by the occurrence of new lesions on nonenhancing T2‐weighted magnetic resonance images of the head was detected in 12 (48%) of 25 patients. Using a semiquantitative polymerase chain reaction we demonstrated significant increases in tumor necrosis factor‐α mRNA expression in peripheral blood mononuclear cells prior to a relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor‐α mRNA expression preceded clinical symptoms by 4 weeks. A similar pattern was observed for lymphotoxin mRNA expression. At the same time, transforming growth factor‐β and interleukin‐10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor‐αwere also observed in 6 patients with stable disease who had active magnetic resonance scans on follow‐up. No correlation of disease activity was observed with interleukin‐1β, ‐4, or ‐6, inferferon gamma or endothelin‐1 mRNA expression. From these data it can be concluded that variations in cytokine mRNA expression in blood mononuclear cells are correlated with disease activity in relapsing‐remitting multiple sclerosis. It may be a valuable parameter to monitor the immunological status of patients in future clinical trials.
Experimental ischemic neuropathy: Salvage with hyperbaric oxygenation
Authors: Kihara Mikihiro , McManis Philip G. , Schmelzer James D. , Kihara Yoriko , Low Phillip A. 
Published: January 2005

AbstractHyperbaric oxygenation is effective in augmenting the delivery of oxygen to tissue, but also causes oxidative stress. As part of our focus on improving peripheral nerve salvage from ischemic fiber degeneration, we evaluated whether hyperbaric oxygenation rescues peripheral nerve, rendered ischemic by microembolization, from ischemic fiber degeneration. The supplying arteries of rat sciatic nerve were embolized with microspheres of 14 μm diameter at moderate (2 × 106) and high (5.6 × 106) doses. Rats were randomized to receive hyperbaric oxygenation treatment (2.5 atm 100% oxygen for 2 hours/day for 7 days beginning within 30 minutes of ischemia), or room air. End points for the embolized limb were (1) behavioral scores (0–11 in increasing levels of limb function), (2) nerve action potential of sciatic‐tibial nerve, (3) nerve blood flow, and (4) histological grade as percentage of fibers undergoing ischemic fiber degeneration (0 = <5%; 1 = 5–25%; 2 = 26–50%; 3 = 51–75%; 4 = >76%). Nerve blood flow and nerve action potential were uniformly absent and more than 90% of fibers had degenerated in both control and treatment groups receiving high doses. Control and treatment groups receiving moderate doses were well matched by level of ischemia (8.5 ± 0.3 [N = 18] vs 7.7 ± 0.4 ml/100 gm/min [N = 18], P > 0.05) but were significantly different by behavior score (5.6 ± 0.7 vs 9.2 ± 0.5 [N = 19], p < 0.001), nerve action potential (1.4 ± 1.0 vs 3.9 ± 0.5 [N = 6], p < 0.05), and histology (2.4 ± 0.4 [N = 5] vs 0.8 ± 0.5 [N = 4], p < 0.05). On single teased fiber evaluation, the predominant abnormality was E (axonal degeneration). We conclude that hyperbaric oxygenation will effectively rescue fibers from ischemic fiber degeneration, providing the ischemia is not extreme.
Genetic identity of Fukuyama‐type congenital muscular dystrophy and Walker‐Warburg syndrome
Authors: Toda Tatsushi , Yoshioka Mieko , Nakahori Yutaka , Kanazawa Ichiro , Nakamura Yusuke , Nakagome Yasuo 
Published: January 2005

AbstractBoth Fukuyama‐type congenital muscular dystrophy (FCMD) and Walker‐Warburg syndrome (WWS) are unusual genetic syndromes consisting of congenital muscular dystrophy and complex malformations of the brain and eye. It has been intensively discussed whether FCMD and WWS belong to the same disease entity or not. We analyzed a family in which 3 siblings were affected with either FCMD or WWS by using polymorphic microsatellites flanking the FCMD locus on chromosome 9q31–33. The results suggested that both FCMD and WWS siblings shared the identical combination of mutations on either allele of the FCMD locus. FCMD and WWS could be “genetically” identical.