bluuebunny/crossref_metadata_2025_split huggingface dataset:
EBNA‐1 sequence variations reflect active EBV replication and disease status or quiescentlatency in lymphocytes
Authors: Wang Jiin‐Tarng , Sheeng Tzung‐Shiahn , Su Ih‐Jen , Chen Jen‐Yang , Chen Mei‐Ru 
Published: January 2003

AbstractEBV infects most of the global population, but only a small percentage of infected individuals develop EBV‐associated malignancies. Host and viral factors may play a role in determining the clinical outcome. Because EBNA‐1 functions as an oriP binding protein and links the episomal viral DNA to metaphase chromosomes, variation of EBNA‐1 has been suggested to contribute to determining the tissue tropism of EBV and the development of various EBV‐associated diseases. Five subtypes have been described, according to the amino acid at residue 487: P‐ala (B95‐8 prototype), P‐thr (aa 487 ala to thr), V‐val, V‐pro and V‐leu. Other studies, however, concluded that EBNA‐1 sequence variation simply reflects the geographical distribution of EBV. To clarify these possibilities, we collected DNA samples from healthy individuals and patients with various EBV‐associated diseases in Taiwan for PCR amplification and DNA sequencing. The results indicate that: 1) V‐val EBNA‐1 was detected in patients with nasopharyngeal carcinoma (NPC) and other EBV‐associated malignant diseases; 2) the prototype P‐ala strain was detected only in peripheral blood lymphocytes; 3) mixed populations of different subtypes of N‐terminal and C‐terminal sequences were observed in samples from one patient with nasopharyngeal carcinoma, one with T lymphoma and one with infectious mononucleosis sample; 4) intermediate variations between P‐ala and V‐val were observed in T‐lymphoma, Hodgkin disease and infectious mononucleosis samples; and 5) in comparison with the major sequences identified in healthy carriers, the EBNA‐1 sequences in peripheral lymphocytes from nasopharyngeal carcinoma were mixed types in 4 of 5 patients, implying increasing frequency of V‐val might correlate with the progression of nasopharyngeal carcinoma. J. Med. Virol. 69:417–425, 2003. © 2003 Wiley‐Liss, Inc.
Enterovirus infection may induce humoral immune response reacting with islet cell autoantigens in humans
Authors: Härkönen Taina , Paananen Anja , Lankinen Hilkka , Hovi Tapani , Vaarala Outi , Roivainen Merja 
Published: January 2003

AbstractMolecular mimicry is one of the mechanisms by which enterovirus infections have been postulated to have a role in the pathogenesis of type 1 diabetes. Immunogenic epitopes in enterovirus capsid protein VP1 and procapsid protein VP0 have sequence similarities with diabetes‐associated epitopes in tyrosine phosphatase IA‐2/IAR and heat shock protein 60. In the present study, documented enterovirus infection was shown to induce humoral responses, that in 7% and 1% of patients cross‐reacted with the known diabetes‐associated epitopes in tyrosine phosphatase IAR and heat shock protein 60, respectively. In contrast, none of the children vaccinated against poliomyelitis had antibodies to the diabetes‐associated epitope of tyrosine phosphatases IA‐2/IAR. The antibody response studied in serum samples from six patients with coxsackievirus A9 infection was mainly targeted to capsid protein VP1. Coxsackievirus A9 infection induced antibodies cross‐reacted with one epitope in heat shock protein 60, but not with epitopes derived from other autoantigens. Most diabetic children had high levels of antibodies to both coxsackievirus and poliovirus derived VP1 peptides but the pattern of reactivity did not differ from that seen in healthy children. The reactivity of linear epitopes derived from autoantigens was low in general and associated with the presence of multiple autoantibodies in the patients. Some linear auto‐epitopes derived from tyrosine phosphatase IA‐2, glutamic acid decarboxylase 65, preproinsulin, and heat shock protein 60 were recognized by sera from diabetic patients, but not by sera from healthy children. In conclusion, enteroviruses may induce immune responses that react with islet cell autoantigens, which is a concern when a putative inactivated enterovirus vaccine is considered. J. Med. Virol. 69:426–440, 2003. © 2003 Wiley‐Liss, Inc.
IgG antibodies to human papillomavirus 16, 52, 58, and 6 L1 capsids: Case‐control study of cervical intraepithelial neoplasia in Japan
Authors: Matsumoto Koji , Yoshikawa Hiroyuki , Yasugi Toshiharu , Nakagawa Shunsuke , Kawana Kei , Takeoka Atsushi , Yaegashi Nobuo , Iwasaka Tsuyoshi , Kanazawa Koji , Taketani Yuji , Kanda Tadahito 
Published: January 2003

AbstractIn Japan, human papillomavirus (HPV) 16, 52, and 58 are most commonly associated with cervical intraepithelial neoplasia (CIN). By contrast, HPV6 is primarily associated with genital warts. This study was designed to evaluate the association between IgG antibody responses to common HPVs and the risk of CIN development within a Japanese population. CIN cases (n = 141) and controls (n = 109) were tested for cervical HPV DNA and serum IgG antibodies to L1 capsids of HPV16, 52, 58, and 6. Seropositivity to HPV16, 52, and 58 L1 capsids was significantly higher in CIN cases than in controls: 27%, 21%, and 31% versus 16%, 11%, and 11%, respectively (P < 0.05). HPV6 L1 seropositivity was not significantly associated with CIN lesions (P = 0.11). Presence of viral DNA for either HPV16, 52, or 58 correlated with a significant antibody response against the homologous L1 capsids but not heterologous L1 capsids. Furthermore, seropositivity to multiple types of HPV16, 52, and 58 was more strongly associated with an increased risk of CIN development than seropositivity to a single type (P for trend <0.001). These findings indicate that IgG antibodies to L1 capsids of HPV16, 52, and 58 represent an increased risk of CIN development, with antibodies to multiple types being indicative of a further increase in risk. The presence of CIN lesions in women with seropositivity to multiple types suggests that viral exposure to a given type may not be protective against infections by other types and subsequent CIN development. J. Med. Virol. 69:441–446, 2003. © 2003 Wiley‐Liss, Inc.
IgG subclasses in human immune response to wild and attenuated (vaccine) Junin virus infection
Authors: Saavedra María del Carmen , Sottosanti Josefa María , Riera Laura , Ambrosio Ana María 
Published: January 2003

AbstractDifferent proportions of IgG subclasses have previously been reported to distinguish the immune response elicited by primary and recurrent viral infections, as well as viral vaccines. The goal of this study was to study the IgG subclasses composition in the immune response of patients with Argentine hemorrhagic fever, and vaccinees with Candid #1 strain of Junin virus. Twenty‐four individuals inoculated with Candid #1 vaccine and 67 patients with Argentine hemorrhagic fever were studied. Blood samples were drawn at 30, 60, and/or 180 days post‐inoculation with Candid #1 and 30, 60, and 90 days after clinical onset of the disease. Specific anti‐Junin virus IgG subclasses were titrated with specific human monoclonal antibody fluorescence isothiocyanate conjugate (FITC) by immunofluorescent assay (IFA). IgG1 anti‐Junin virus was found in every subject studied and IgG3 was also detected in some patients with a severe form of Argentine hemorrhagic fever. IgG2 and IgG4 were not detected in any serum sample studied. The mean titer of specific IgG1 in vaccinees was significantly lower than in patients with Argentine hemorrhagic fever (P < 0.05), but no difference was found between mild and severe cases of the disease (P > 0.05). The results of this study demonstrated a central role of IgG1 in human recovery from infection with every strain of Junin virus, an observation stressed by the immune response to Candid #1 vaccine, which resulted in no difference in IgG subclasses composition from that found in mild cases of Argentine hemorrhagic fever. J. Med. Virol. 69:447–450, 2003. © 2003 Wiley‐Liss, Inc.
Differential efficacy of a synthetic antagonist of VLA‐4 during the course of chronic relapsing experimental autoimmune encephalomyelitis
Authors: Cannella Barbara , Gaupp Stefanie , Tilton Ronald G. , Raine Cedric S. 
Published: January 2003

AbstractThe integrin VLA‐4 has been shown to play a key role in the entry of antigen‐specific T cells into the CNS during autoimmune demyelination. Treatment of animals with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, with antibodies to VLA‐4 is known to suppress acute disease. In the present study, a synthetic antagonist of VLA‐4 (TBC 3486) was injected subcutaneously into mice adoptively sensitized for chronic relapsing EAE. TBC 3486 was administered daily for 14 days at early (before acute signs) and late time points (during chronic disease). Early treatment led to marked delay in disease onset and reduction in clinical severity and demyelination. After termination of treatment, clinical severity remained lower than in controls for more than 1 week. TBC 3486‐treated animals showing no clinical signs (at the height of disease in controls) displayed moderate levels of inflammation but little damage to myelin. Late administration of TBC 3486 to animals with chronic EAE had no effect clinically. Immunocytochemistry and Western blotting of CNS tissue from acutely treated animals supported a moderate shift toward a Th2‐type cytokine profile after treatment. Thus, TBC 3486 effectively delayed and reduced the acute (but not chronic) phase of EAE, and this amelioration correlated with changes in the inflammatory molecule profile. © 2002 Wiley‐Liss, Inc.
Distribution of γ‐aminobutyric acid receptors in cultured adrenergic and noradrenergic bovine chromaffin cells
Authors: Castro Enrique , González María Pilar , Oset‐Gasque María Jesús 
Published: January 2003

AbstractFluorescence imaging techniques for recording cytosolic [Ca2+]i from single chromaffin cells were used to characterize and discriminate between cell subpopulations containing γ‐aminobutyric acid (GABA)A and GABAB receptor subtypes. By combining this methodology with the immunoidentification of individual chromaffin cells using specific antibodies against tyrosine hydroxylase (TH), phenyl‐etanolamine‐N‐methyl transferase (PNMT), and glutamic acid decarboxylase (GAD) linked to different fluorescent probes, we have been able to ascribe single‐cell calcium responses to identified adrenergic and noradrenergic chromaffin cells. GAD enzyme is present in 30% of the chromaffin cell population, located primarily in adrenergic cells; 86% of GAD+ cells were also PNMT+. GAD expression was not correlated with the presence of GABA receptors. GABA‐responsive cells were found with equal frequency in the GAD+ and GAD− groups. However, the expression of GABA receptors was correlated with the adrenergic phenotype. [Ca2+]i responses to GABA were found more frequently in adrenergic than in noradrenergic cells. GABAA receptors are more evenly distributed; about 90% of GABA‐responsive cells have them. GABAB receptors have a more restricted distribution (present in 45% of responding cells). The coexpression of both GABAA and GABAB subtypes is the rule; only a minor subpopulation (about 12%) displays exclusively GABAB receptors. GABA receptor subtypes are distributed in a similar way when chromaffin cells are separated according to GAD+/GAD− or PNMT+/PNMT− classifications, with only minor differences. These data indicate that the intrinsic GABAergic system in the adrenal medulla is not designed as a paracrine model in which a group of cells specializes in transmitter synthesis and a different group serves as a specific target. © 2002 Wiley‐Liss, Inc.
Glutamate and aspartate do not exhibit the same changes in their extracellular concentrations in the rat striatum after N‐methyl‐D‐aspartate local administration
Authors: Parrot Sandrine , Bert Lionel , Renaud Bernard , Denoroy Luc 
Published: January 2003

AbstractTo determine whether glutamate (Glu) and aspartate (Asp) undergo a similar regulation of their extracellular levels, Glu and Asp were simultaneously monitored in the striatum of anesthetized rats after local N‐methyl‐D‐aspartate (NMDA) receptor stimulation, using 1‐min in vivo microdialysis coupled to capillary electrophoresis with laser‐induced fluorescence detection. Application of NMDA (10 min, 10–3 M) through the dialysis probe induced 1) an increase (+50%) in Asp during the NMDA administration and 2) a surprising biphasic effect on Glu, with a rapid increase (+30%) and a return to baseline before the end of NMDA application, followed by a second increase (+40%) occurring after and linked to the end of NMDA administration. When studied in the presence of 10 μM tetrodotoxin (TTX) or 0.1 mM Ca2+, the increase in Asp was partially TTX‐dependent, and the early increase in Glu appeared to be partially TTX and Ca2+ dependent, whereas the second increase in Glu was not. The second increase in Glu level was still present when NMDA antagonists (AP5 or MK‐801) were administered at the end of NMDA application. Finally, only extracellular Asp was increased through application of lower NMDA concentrations (10–4 M, 10–5 M), whereas extracellular Glu was not affected. In conclusion, these results suggest a differential control of Glu and Asp extracellular levels in rat striatum by distinct mechanisms linked to NMDA receptors and involving neuronal or nonneuronal release. © 2002 Wiley‐Liss, Inc.
Quantification of transcriptional activities of reporter gene constructs in primary cultures of sympathetic neurons
Authors: Pajak Fabrice , De Gois Stéphanie , Houhou Leïla , Védrine Christophe , Mallet Jacques , Berrard Sylvie 
Published: January 2003

AbstractPrimary cultures of sympathetic neurons provide an attractive cellular model for investigating the mechanisms of neurotransmitter phenotypic plasticity. However, it has not been possible to transfect these neurons by conventional techniques, and this has been a major impediment to molecular investigations of neuronal gene expression in this system. Here, reporter plasmids were transferred into the nuclei of cultured sympathetic neurons by microinjection. We developed and improved this procedure and were able to measure the transcriptional activities of two coinjected promoters in small groups of neurons, and even from a single neuron. Promoter activities can thus be quantified and normalized relative to that of a constitutively expressed promoter, allowing correction for variability in the injection and assay procedures. High and low promoter activities can be reliably quantified. Importantly, this method can be used not only for reporter plasmids but also for DNA fragments containing only a promoter and reporter gene without any vector sequence that might interfere with promoter. Using this approach, we measured neuronal promoter activities and found that one promoter region of the gene encoding choline acetyltransferase was up‐regulated by more than sevenfold by leukemia inhibitory factor. This method thus provides the means to investigate the function of neuronal genes and the mechanisms that regulate their transcription in cultured sympathetic neurons. © 2002 Wiley‐Liss, Inc.
γ1 Laminin and its biologically active KDI‐domain may guide axons in the floor plate of human embryonic spinal cord
Authors: Wiksten Markus , Liebkind Ron , Laatikainen Timo , Liesi Päivi 
Published: January 2003

AbstractImmunocytochemistry, in situ hybridization and Matrigel‐embedded cultures were used to investigate the distribution of laminins during development of the human embryonic spinal cord (7–11 weeks). Our results indicate that α1, β1, β3 and γ1 laminins localize as punctate deposits in the floor plate region in association with commissural fibers crossing the ventral midline. In addition, the neurite outgrowth domain of γ1 laminin accumulates heavily in the floor plate region, in the notochord and in GFAP‐immunoreactive glial fibers of the embryonic spinal cord. In culture experiments, the biologically active KDI‐domain of γ1 laminin selectively attracted directional outgrowth of neurites from explants of the dorsal spinal cord. The spatial and temporal colocalization of punctate deposits of laminins with nerve fibers crossing the ventral midline, and the guidance of neurites by the KDI‐peptide domain, indicate that laminins, specifically the γ1 laminin, may be involved in guidance of axons during embryonic development of the human spinal cord. © 2002 Wiley‐Liss, Inc.
Loss of nicotinic receptors induced by beta‐amyloid peptides in PC12 cells: Possible mechanism involving lipid peroxidation
Authors: Guan Zhi‐Zhong , Yu Wen‐Feng , Shan Ke‐Ren , Nordman Tomas , Olsson Jerker , Nordberg Agneta 
Published: January 2003

AbstractThe mechanisms involved in the loss of nicotinic acetylcholine receptors (nAChRs), seen in brains of patients with Alzheimer's disease (AD) and in cultured cells treated by β‐amyloid peptides (Aβs), remain elusive. We give results to show that lipid peroxidation induced directly by Aβ might be involved in the deficits of nAChRs. In the study, PC12 cells were treated by addition of 5 μM of Aβ25–35 and Aβ1–40, respectively, with or without a antioxidant, vitamin E. Besides significantly decreased MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5,diphenyltetrazolium bromide) reduction, an increased lipid peroxidation was detected in the cells, but no protein oxidation. Significant reductions in [3H]epibatidine and [125I]α‐bungarotoxin binding sites and in the protein levels of the α3 and α7 nAChR subunits were observed in the cells treated with Aβs. Furthermore, Aβ25–35 decreased the level of ubiquinone‐9 in PC12 cells, but did not change the amount of cholesterol, providing further evidence for lipid peroxidation. Interestingly, when PC12 cells were pretreated by antioxidant before the addition of Aβs, the lipid peroxidation and the decreased ubiquinone resulted from Aβs were prohibited. The decreases of nAChR binding sites and subunit proteins resulted from Aβs were mostly prevented by the pretreatment with antioxidant. These findings suggest that lipid peroxidation stimulated by Aβs might be a mechanism for the loss of nAChRs associated with the pathogenesis of AD. © 2002 Wiley‐Liss, Inc.
Differential expression of L‐ and S‐MAG upon cAMP stimulated differentiation in oligodendroglial cells
Authors: Erb M. , Steck A.J. , Nave K.A. , Schaeren‐Wiemers N. 
Published: January 2003

AbstractMyelin‐associated glycoprotein (MAG), an immunoglobulin‐like cell signaling protein involved in axon‐glial interactions, displays two intracellular C‐termini as a result of alternative mRNA splicing. During brain development, the two MAG mRNAs that encode L‐MAG and S‐MAG differ in their relative abundance. We have investigated the differential expression of L‐ and S‐MAG upon cAMP treatment in the oligodendroglial cell line Oli‐neu, a cell line able to differentiate in vitro. We have engineered GFP and VSVG fusions by small insertions into the alternatively spliced exons of the cloned MAG gene and reintroduced them into Oli‐neu cells. The individually tagged MAG isoforms were expressed under the control of the MAG promoter and regulatory region. In this system, L‐MAG was the predominant isoform before the stimulation of cells with cAMP, whereas upon cAMP treatment the S‐MAG isoform was predominantly expressed in cells with a high degree of morphological differentiation. We suggest that the regulation of the MAG alternative splicing and the morphological differentiation in oligodendrocytes are controlled both by the same cAMP‐responsive differentiation step. © 2002 Wiley‐Liss, Inc.
Effects of peroxisome proliferator‐activated receptor‐γ agonists on central nervous system inflammation
Authors: Kielian Tammy , Drew Paul D. 
Published: January 2003

AbstractPeroxisome proliferator‐activated receptor‐γ (PPAR‐γ) plays a critical role in glucose and lipid metabolism. More recently, PPAR‐γ ligands have been reported to inhibit the expression of proinflammatory molecules by monocytes/macrophages. Of relevance to CNS disease is that PPAR‐γ agonists have been demonstrated to have similar effects on microglia. PPAR‐γ agonists also ameliorate experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. This Mini‐Review summarizes the effects of PPAR‐γ agonists in mediating immune responses and the potential of these agonists in the treatment of inflammatory disorders of the CNS. © 2002 Wiley‐Liss, Inc.
Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin‐C during acute to chronic maturation of spinal cord scar tissue
Authors: Tang Xiufeng , Davies Jeannette E. , Davies Stephen J.A. 
Published: January 2003

AbstractPrevious studies have correlated the failure of axon regeneration after spinal cord injury with axons contacting scar tissue rich in chondroitin sulfate proteoglycans (CSPGs; Davies et al., 1999). In the present study, we have conducted immunohistochemical and quantitative Western blot analysis of five axon‐growth‐inhibitory CSPGs and tenascin‐C within stab injuries of adult rat spinal cord at time points ranging from 24 hr to 6 months post injury. Quantitative Western blot analysis showed robust increases in neurocan, tenascin‐C, and NG2 levels by 24 hr, suggesting that these molecules play a role in preventing axon regeneration across acutely forming scar tissue. Peak levels of 245/130 kD neurocan, NG2, and 250/200 kD tenascin‐C were reached at 8 days, with maximum levels of phosphacan and 140/80 kD brevican attained later, at 1 month post injury. Versican V2 protein levels, however, displayed an opposite trend, dropping below unlesioned spinal cord values at all time points studied. Confocal microscopy at 8 days post injury revealed heightened immunoreactivity for phosphacan, NG2, and tenascin‐C, particularly within fibronectin+ scar tissue at lesion centers. In contrast, neurocan was displayed within lesion margins on the processes of stellate NG2+ cells and, to a much lesser extent, by astrocytes. At 6 months post injury, 130 kD neurocan, brevican, and NG2 levels within chronic scar tissue remained significantly above control. Our results show novel expression patterns and cell associations of inhibitory CSPGs and tenascin‐C that have important implications for axon regeneration across acute and chronic spinal cord scar tissue. © 2002 Wiley‐Liss, Inc.