bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Positive Autoregulatory Loop of LMP1 Expression and STAT Activation in Epithelial Cells Latently Infected with Epstein-Barr Virus
Authors: Chen Honglin , Hutt-Fletcher Lindsey , Cao Liang , Hayward S. Diane 
Published: March 2003

ABSTRACTSTAT3 and STAT5 are constitutively activated and nuclear in nasopharyngeal carcinoma (NPC) cells. In normal signaling, STATs are only transiently activated. To investigate whether Epstein-Barr virus (EBV), and in particular the protein LMP1, contributes to sustained STAT phosphorylation and activation in epithelial cells, we examined STAT activity in two sets of paired cell lines, HeLa, an EBV-converted HeLa cell line, HeLa-Bx1, the NPC-derived cell line CNE2-LNSX, and an LMP1-expressing derivative, CNE2-LMP1. EBV infection was associated with a significant increase in the tyrosine-phosphorylated forms of STAT3 and STAT5 in HeLa-Bx1 cells. This effect correlated with LMP1 expression, since phosphorylated STAT3 and STAT5 levels were also increased in CNE2-LMP1 cells relative to the control CNE2-LNSX cells. No change was observed in STAT1 or STAT6 phosphorylation in these cell lines, nor was there a significant change in the levels of total STAT3, STAT5, STAT1, or STAT6 protein. Tyrosine phosphorylation allows the normally cytoplasmic STAT proteins to enter the nucleus and bind to their recognition sequences in responsive promoters. The ability of LMP1 to activate STAT3 was further established by immunofluorescence assays in which coexpression of LMP1 in transfected cells was sufficient to mediate nuclear relocalization of Flag-STAT3 and by an electrophoretic mobility shift assay which showed that LMP1 expression in CNE2-LNSX cells was associated with increased endogenous STAT3 DNA binding activity. In addition, the activity of a downstream target of STAT3, c-Myc, was upregulated in HeLa-Bx1 and CNE2-LMP1 cells. A linkage was established between interleukin-6 (IL-6)- and LMP1-mediated STAT3 activation. Treatment with IL-6 increased phosphorylated STAT3 levels in CNE2-LNSX cells, and conversely, treatment of CNE2-LMP1 cells with IL-6 neutralizing antibody ablated STAT3 activation and c-Myc upregulation. The previous observation that STAT3 activated the LMP1 terminal repeat promoter in reporter assays was extended to show upregulated expression of endogenous LMP1 mRNA and protein in HeLa-Bx1 cells transfected with a constitutively activated STAT3. A model is proposed in which EBV infection of an epithelial cell containing activated STATs would permit LMP1 expression. This in turn would establish a positive feedback loop of IL-6-induced STAT activation, LMP1 and Qp-EBNA1 expression, and viral genome persistence.
Intracellular Assembly and Secretion of Recombinant Subviral Particles from Tick-Borne Encephalitis Virus
Authors: Lorenz Ivo C. , Kartenbeck Jürgen , Mezzacasa Anna , Allison Steven L. , Heinz Franz X. , Helenius Ari 
Published: March 2003

ABSTRACT
It is believed that flavivirus assembly occurs by intracellular budding of the nucleocapsid into the lumen of the endoplasmic reticulum (ER). Recombinant expression of tick-borne encephalitis (TBE) virus envelope proteins prM and E in mammalian cells leads to their incorporation into enveloped recombinant subviral particles (RSPs), which have been used as a model system for studying assembly and entry processes and are also promising vaccine candidates. In this study, we analyzed the formation and secretion of TBE virus RSPs and of a membrane anchor-free E homodimer in mammalian cells. Immunofluorescence microscopy showed that E was accumulated in the lumen of the ER. RSPs were observed by electron microscopy in the rough and smooth ER and in downstream compartments of the secretory pathway. About 75% of the particles appeared to be of the size expected for RSPs (about 30 nm in diameter), but a number of larger particles and tubular structures were also observed in these compartments. Secretion of membrane anchor-free E dimers was detected 30 min after synthesis of prM and E, and secretion of RSPs was detected 1 h after synthesis of prM and E. We also found that the presence of the single N-linked oligosaccharide side chain on the E protein and its trimming by glucosidases was necessary for secretion of RSPs and truncated E dimers. Our results suggest that incorporation of prM and E into RSPs occurs at the ER membrane without other viral elements being required, followed by rapid transport along the compartments of the secretory pathway and secretion. Moreover, the carbohydrate side chain of E is involved in at least one assembly or transport step.
Retinal influences specify cortico‐cortical maps by postnatal day six in rats and mice
Authors: Olavarria Jaime F. , Hiroi Ryoko 
Published: March 2003

AbstractStudies of callosal projections in striate cortex show that the retina is involved in the development of topographical connections. In normal animals callosal fibers connect retinotopically corresponding, nonmirror‐symmetric cortical loci, whereas in animals bilaterally enucleated at birth, callosal fibers connect topographically mismatched, mirror‐symmetric loci. Moreover, in rodents the overall pattern of visual callosal connections is adult‐like by postnatal day 12 (P12). In this study we delayed the onset of retinal deafferentation in rats and mice in order to determine the period when retinal influences are critically needed for the development of retinotopically matched callosal linkages. Callosal maps were revealed by placing small injections of retrogradely and anterogradely transported tracers into different loci of lateral striate cortex. We found that the patterns of callosal linkages in rats enucleated at P12, P8, and P6 were nonmirror‐symmetric, as in normally reared rats. In contrast, the patterns of linkages in rats enucleated at P4 closely resembled the mirror‐symmetric pattern seen in rats enucleated at birth (P0). A similar reversal in topography (from symmetric to nonsymmetric) occurred in mice when enucleation was delayed from P4 to P6. These findings indicate that retinal input prior to P6, but not prior to P4, is sufficient for specifying normal callosal topography. Moreover, they suggest that development of retinotopically matched callosal linkages depends critically on retinal influences during a brief period between P4 and P6, when callosal connections are still very immature. J. Comp. Neurol. 459:156–172, 2003. © 2003 Wiley‐Liss, Inc.
Bayesian hierarchical models in ecological studies of health–environment effects
Authors: Richardson Sylvia , Best Nicky 
Published: March 2003

AbstractWe describe Bayesian hierarchical models and illustrate their use in epidemiological studies of the effects of environment on health. The framework of Bayesian hierarchical models refers to a generic model building strategy in which unobserved quantities (e.g. statistical parameters, missing or mismeasured data, random effects, etc.) are organized into a small number of discrete levels with logically distinct and scientifically interpretable functions, and probabilistic relationships between them that capture inherent features of the data. It has proved to be successful for analysing many types of complex epidemiological and biomedical data. The general applicability of Bayesian hierarchical models has been enhanced by advances in computational algorithms, notably those belonging to the family of stochastic algorithms based on Markov chain Monte Carlo techniques.In this article, we review different types of design commonly used in studies of environment and health, give details on how to incorporate the hierarchical structure into the different components of the model (baseline risk, exposure) and discuss the model specification at the different levels of the hierarchy with particular attention to the problem of aggregation (ecological) bias. Copyright © 2003 John Wiley & Sons, Ltd.
Hypermethylation, but not LOH, is associated with the low expression of MT1G and CRABP1 in papillary thyroid carcinoma
Authors: Huang Ying , de la Chapelle Albert , Pellegata Natalia S. 
Published: March 2003

AbstractWe previously obtained gene expression profiles of 8 matched papillary thyroid carcinoma (PTC) and normal tissues using DNA microarrays. To identify novel tumor suppressor genes involved in thyroid carcinogenesis, we here analyze genes showing lower expression in PTC tumors than in normal thyroid tissues. A search for loss of heterozygosity (LOH) in 49 regions that harbor consistently down‐regulated genes revealed LOH in only 4 regions and in just a very small number of tumors. To determine whether the underexpression might be due to promoter methylation, we used combined bisulfite restriction analysis and bisulfite sequencing to study 7 underexpressed genes. Loss of expression of MT1G and CRABP1 is accompanied by hypermethylation in the 5′ regions of these genes, but methylation was not seen in other genes tested. Combined treatment with the DNA methyltransferase inhibitor 5‐aza‐2′‐deoxycytidine (5‐Aza‐dC) and the histone deacetylase inhibitor trichostatin A (TSA) resulted in demethylation and re‐expression of the MT1G gene in the cell line K2. Treatment with 5‐Aza‐dC alone restored CRABP1 expression in a colorectal cancer cell line, SW48. In conclusion, LOH is a remarkably rare mechanism of loss of gene function in PTC. In contrast, hypermethylation of promoter CpG islands seems to occur at higher frequency. MT1G and CRABP1 are novel genes that are likely involved in the pathogenesis of sporadic PTC. © 2003 Wiley‐Liss, Inc.
Overexpression of Id‐1 is associated with poor clinical outcome in node negative breast cancer
Authors: Schoppmann Sebastian F. , Schindl Monika , Bayer Guenther , Aumayr Klaus , Dienes Julia , Horvat Reinhard , Rudas Margaretha , Gnant Michael , Jakesz Raimund , Birner Peter 
Published: March 2003

AbstractId‐1 is an important regulator of cellular growth and differentiation and controls malignant progression of breast cancer cells. The aim of our study was to assess the clinical impact of Id‐1 expression in breast cancer, i.e., its potential impact on prognosis and prediction of treatment response. Id‐1 protein expression was determined immunohistochemically in 191 patients with lymph‐node negative breast cancer, and univariate and multivariate survival analysis was carried out. Fifteen (7.9%) specimens showed strong expression, 75 (39.3%) moderate, 55 (28.8%) weak expression and 46 (24.1%) cases no expression of Id‐1. Patients with strong or moderate Id‐1 expression had a significant shorter overall (p = 0.003, Cox regression) and disease‐free survival (p = 0.01, Cox regression) compared to those with absent or low expression. Progesterone receptor density was significantly higher in breast cancers with absent/low Id‐1 expression compared to those with moderate/strong expression (p < 0.001, t‐test). Id‐1 expression was significantly stronger in cases positive for p16INK4a expression compared to those negative for p16 (p = 0.049, Mann‐Whitney test). The influence of Id‐1 on clinical outcome seems much stronger in patients with negative estrogen receptor status compared to those with positive status, who received receptor antagonists as adjuvant therapy in most cases. Overexpression of Id‐1 protein represents a strong independent prognostic marker in node negative breast cancer, and future therapies inhibiting Id‐1 expression might be beneficial for these patients. Our results also suggest that due to the apparent interaction of Id‐1 with the steroid‐receptor system in breast cancer, hormonal therapies might influence Id‐1 expression and its impact on clinical outcome. © 2003 Wiley‐Liss, Inc.
Approximate urban area call drop‐out probability estimation in mobile multi‐satellite systems
Authors: Perez‐Fontan F. , Vazquez‐Castro M.A. , Enjamio C. , Mariño P. , Pita J. 
Published: March 2003

AbstractLand mobile satellite (LMS) systems require constellations of multiple satellites to compensate for the large blockage probabilities suffered in urban areas. An approximate methodology based on the street masking function (MKF) or mask concept is presented for the evaluation of system availability. MKFs are graphical representations of the angles (azimuths and elevations) for which a satellite is visible from the terminal's location in the street. MKFs can also be used in the evaluation of second order statistics such as durations of fades or connections. In this paper, the applicability of the mask concept is demonstrated by performing a study of the probability of successful call completion in a LEO‐based satellite telephony service. Copyright © 2003 John Wiley & Sons, Ltd.
Going back to the roots: effective utilisation of HLA typing information for bone marrow registries requires full knowledge of the DNA sequences of the oligonucleotide reagents used in the testing
Authors: Helmberg W. , Hegland J. , Hurley C.K. , Maiers M. , Marsh S.G.E. , Müller C. , Rozemuller E.H. 
Published: March 2003

Abstract:Information obtained by DNA‐based HLA typing assays is more detailed and of higher quality than that obtained by conventional serological techniques. Nevertheless, it is common for data acquired in this way to be presented in the more familiar serological format. In many cases this representation can lead to significant loss of information, which may only become apparent at a later time, with the discovery of novel allele sequences. DNA‐based typing methods, such as sequence‐specific oligonucleotide probing (SSOP) or sequence‐specific priming (SSP) generate fragmentary sequence data which is information rich. An alternative to assigning allele names to these fragments is to simply store the sequence data itself without interpretation. Bone marrow donor repositories can then be searched directly with sequence information, which though complex is more complete, rather than searching by derivative allele names.
Detection of KIR2DL4 alleles by sequencing and SSCP reveals a common allele with a shortened cytoplasmic tail
Authors: Witt C.S. , Martin A. , Christiansen F.T. 
Published: March 2003

Abstract:Single‐stranded conformation polymorphism (SSCP) by capillary electrophoresis was assessed as a screening and typing method for alleles of KIR2DL4. Exon 6 was investigated as this exon was reported to include three polymorphic nucleotides. Exon 6, intron 6 and exon 7 were amplified as a single polymerase chain reaction (PCR) product of 650 bp from genomic DNA. The PCR product was sequenced and analysed by SSCP. Exon 7 was found to be invariant. Only two nucleotides were found to be polymorphic in exon 6 and another three were found in intron 6. Strong linkage disequilibrium was found between the polymorphic nucleotides resulting in the presence of three alleles in a panel of 20 cell lines. Two alleles differed within intron 6 while the third allele differed at two nucleotides in exon 6. All six possible genotypes were distinguishable by SSCP providing information from both the forward and reverse primers was used. Exon 6 of one allele was one nucleotide shorter than that of the other alleles and the resulting frame shift is predicted to produce a truncated cytoplasmic tail due to a premature stop codon four codons into exon 7. SSCP was found to be an efficient method of typing exons 6 and 7 in a panel of 46 bone marrow donors. All three alleles were found to be common and one was in strong linkage disequilibrium with the presence of another KIR sequence KIR3DS1.
The potential role of rapamycin in pediatric transplantation as observed from adult studies
Authors: Kahan Barry D. 
Published: March 2003

Kahan BD. The potential role of rapamycin in pediatric transplantation as observed from adult studies.Pediatr Transplantation 1999: 3: 175–180. © Munksgaard, 1999Abstract: Although pediatric patient and renal graft survival rates have shown marked improvements during the past decade, the persistent toxicities of immunosuppressive drugs and chronic allograft attrition remain major obstacles in transplant therapy. Results in adult patients suggest that complete steroid withdrawal is possible in the majority of recipients under treatment with a cyclosporin A–rapamycin (CsA–RAPA) regimen. Furthermore, preliminary studies suggest that a marked reduction in the dose of CsA may be possible under the umbrella of RAPA coverage. The gain in immunosuppressive efficacy afforded by RAPA has not only been obtained without an increased morbidity owing to infectious or neoplastic causes, but also with the potential for reducing the incidence and/or progression of chronic rejection.
Tuberculosis in renal transplant recipients
Authors: Lattes R. , Radisic M. , Rial M. , Argento J. , Casadei D. 
Published: March 2003

Abstract:Tuberculosis (TB) has been described in kidney transplant recipients as an infection with predominantly pulmonary involvement. We report the impact of TB in kidney transplantation. Clinical records of adult kidney recipients, transplanted between 1 January 1986 and 31 December 1995 were analyzed for sex, age, graft origin, immunosuppressive therapy, TB sites, diagnostic methods and concomitant infections. Annual incidence, mean time of onset, relation to rejection treatment, tuberculin skin test (PPD) and outcome were analyzed. Patients with a history of TB or graft loss in the first month were excluded. TB was diagnosed in 14 of 384 (3.64%). Mean age at transplantation was 35 years. Twelve of these received the graft from a living donor. All had triple immunosuppression with cyclosporine. Ten had pulmonary TB, three extrapulmonary infection and one disseminated disease. In 13 cases an invasive diagnostic procedure was performed.Mycobacterium tuberculosiscultures were positive in all cases; microscopy revealed acid‐fast bacilli (AFB) in 6, and adenosine deaminase was elevated in CSF and pleural effusion in 2. Annual incidence varied from 0% to 3.1%. At the time of TB presentation 8 patients had other concomitant infections (cytomegalovirus, nocardia,Pneumocystis carinii, disseminated herpes simplex virus). Median time of onset was 13 months. Diagnostic results became available post‐mortem in 2 cases, and one had TB in a failing allograft. TB was treated with 4 drugs including rifampin in 10 patients. Cyclosporine was discontinued in one, lowered in one and increased in 8. During treatment 5 patients had rejection episodes. At 1 year, graft survival was 72.7% and patient survival 90.9%. TB was more prevalent when recipient and donor were both PPD positive. In summary: although TB is a growing threat in the transplant setting, early and aggressive diagnosis with meticulous monitoring of immunosuppression allows a successful outcome for both patient and graft. Optimal prophylaxis guidelines have yet to be completely defined.
Opportunistic infections after blood and marrow transplantation
Authors: Wingard J.R. 
Published: March 2003

Abstract:Opportunistic infections are major causes of morbidity and mortality following bone marrow transplantation. Technological advances in stem cell procurement, the introduction of hematologic growth factors to speed engraftment, the development of new immunosuppressive regimens to control graft‐versus‐host disease (GVHD), the development of technology to perform graft engineering with removal of T lymphocytes in toto or subpopulations of T lymphocytes, the use of molecular techniques to optimize donor and recipient matching, advances in blood banking, and development of international donor registries, are among the various factors that have led to tremendous changes in transplant practices. Because of such changes in transplant practices, along with the advent of new antimicrobial agents, and development of infection control measures affecting pathogen exposure, alterations in the interplay between host and potential pathogens have occurred. Shifts in the incidence and types of opportunistic pathogens are taking place. Several historically important infectious syndromes are today well controlled; others have diminished in importance early after transplant but are more problematic at a later time; new emerging pathogens are being recognized due to selection pressures from antimicrobial usage and new hosts, such as recipients of alternate donor allogeneic transplant procedures, with even more profound and prolonged immune suppression. Such shifts and new syndromes pose continuing new challenges to the transplant clinician (
Note).
The therapeutic prescription for the organ transplant recipient: the linkage of immunosuppression and antimicrobial strategies
Authors: Rubin R.H. , Ikonen T. , Gummert J.F. , Morris R.E. 
Published: March 2003

Abstract:Infection and rejection, the two major barriers to successful organ transplantation, are closely linked, with immunosuppressive therapy being central to the pathogenesis of both. After almost two decades when azathioprine and prednisone, supplemented by antilymphocyte antibody therapy, were the cornerstones of post‐transplant immunosuppressive programs, there has been a major increase in the therapeutic armamentarium available to treat rejection: cyclosporine, tacrolimus, mycophenolate mofetil, rapamycin, and antibodies directed against the interleukin‐2 receptor. These agents are potent inhibitors of microbial specific T cell function, thus potentiating opportunistic infection with herpes group viruses, fungal and mycobacterial species,Strongyloides stercoralis, and a variety of intracellular pathogens. The mechanisms by which each of these drugs exerts its effects are an important determinant of the antimicrobial strategies that will be necessary to combat infection. Indeed, strategies to limit these infections are being linked to the nature of the immunosuppressive therapy required in a particular patient. Thus, the therapeutic prescription for the transplant patient is said to have two components: an immunosuppressive component to prevent and treat rejection, and an antimicrobial one to make it safe. In addition to using antimicrobial agents therapeutically, in the transplant patient prevention is stressed in which antibiotics are deployed prophylactically or preemptively (Note).
Infections of the central nervous system in transplant recipients
Authors: Singh N. , Husain S. 
Published: March 2003

Abstract:Central nervous system (CNS) infections, accounting for 4–29% of CNS lesions in transplant recipients, are a significant post‐transplant complication. Focal CNS infectious lesions or brain abscesses have been documented in 0.36–1% of the transplant recipients. Mycelial fungi, particularlyAspergillus, are by far the most frequent etiologies of post‐transplant brain abscesses. Bacteria, with the exception ofNocardia, are rarely associated with brain abscesses in transplant recipients. Time of onset and concurrent extraneural lesions have implications relevant towards invasive diagnostic procedures in transplant recipients with brain abscesses. Meningoencephalitis in transplant recipients is predominantly due to viruses, e.g., herpesviruses, and less frequently due toListeria monocytogenes,Toxoplasma gondii, andCryptococcus. Despite a wide, and at times perplexing array of opportunistic pathogens that can cause CNS infections, the temporal association of the infection with the time elapsed since transplantation, risk factors, clinical manifestations, and neuroimaging characteristics of the lesion can allow a reasoned and rational approach towards the recognition, diagnosis, and appropriate management of CNS infections in transplant recipients.