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contribution of neuroimmune mechanisms to airway inflammation and remodeling during and after respiratory syncytial virus infection.a number of studies have implicated severe infections early in life as a risk factor for the subsequent development of asthma. in particular it has been suggested that respiratory syncytial virus (rsv) infection may enhance the development of "allergic" inflammatory responses when the host is exposed to allergens after an episode of bronchiolitis. it has also been suggested that neuronal mechanisms are important in rsv infection and subsequent airway hyperreactivity. recently we advanced the hyp ...200312671455
respiratory syncytial virus bronchiolitis and the pathogenesis of childhood asthma.there is now convincing evidence that children who develop lower respiratory symptoms during infection with respiratory syncytial virus (rsv) in early life are at increased risk of developing asthma-like symptoms during the school years. what determines this association is not well-understood, but increased likelihood of allergic sensitization plays a minor role, if any, as a determinant of post-rsv wheeze. current evidence suggests that both genetic and environmental factors determine the type ...200312671456
treatment of respiratory syncytial virus: antiviral therapies.treatment of respiratory syncytial virus (rsv) in infants with bronchiolitis is complicated because of the multifactorial nature of this infection. the signs and symptoms of rsv result from a combination of direct viral cytopathic effects, host inflammatory responses that lead to airway obstruction and bronchoconstriction. it is logical that therapies targeting just one of these processes might be minimally effective, at best. thus an important goal is to identify patients at risk and intervene ...200312671458
clinical experience with respiratory syncytial virus vaccines.respiratory syncytial virus (rsv) infection is at times associated with life-threatening lower respiratory tract illness in infancy. severe infection during the first year of life may be an important risk factor or indicator for the development of asthma in early childhood. severe infections primarily occur in healthy infants, and young infants and children with specific risk factors. however, rsv causes respiratory infections in all age groups. indeed it is now recognized that rsv disease is re ...200312671459
mucosal gene expression vaccine: a novel vaccine strategy for respiratory syncytial virus.a number of approaches have been used in attempts to develop a safe and effective vaccine for respiratory syncytial virus (rsv) infection. this article describes an effective prophylactic intranasal gene transfer strategy utilizing chitosan-dna nanospheres [the mucosal gene expression vaccine (mgxv)], containing a mixture of plasmid dnas encoding rsv antigens. in a mouse model of rsv infection, a single administration of mgxv (25 microg/mouse) results in a significant reduction of viral titers a ...200312671460
two-year periodicity of respiratory syncytial virus epidemics in switzerland.the annual respiratory syncytial virus (rsv) epidemics vary in time and severity. the aims of this study were (1) to describe the time-related pattern of rsv epidemics in switzerland and (2) to deduce the most effective time period for administration of prophylactic measures to high-risk patients.200312682811
identification of contaminating adenovirus type 1 in the atcc reference strain of respiratory syncytial virus a2 (vr-1302).atcc reference strain of respiratory syncytial virus a-2 (vr-1302), which was originally isolated from the lower respiratory tract of an infant (lewis et al., 'med. j. aust. 2 (1961) 932'), is contaminated with adenovirus type 1. the presence of adenovirus was deduced from microscopic observation of cpe in hep-2 cells and confirmed by electron microscopy, pcr, serological typing and immunofluoresence. since rsv a2 is used worldwide as a representative virus of rsv type a viruses, and because the ...200312686423
the childhood origins of asthma (coast) study.although asthma is probably a heterogeneous disease or syndrome, three factors and/or events consistently emerge for their ability to significantly influence asthma inception in the first decade of life: immune response aberrations, which appear to be defined best by the concept of cytokine dysregulation; lower respiratory tract infections, in particular respiratory syncytial virus (rsv); and some form of gene-environment interaction that needs to occur at a critical time-period in the developme ...200212688623
identification of amino acids that are critical to the processivity function of respiratory syncytial virus m2-1 protein.the m2-1 protein of respiratory syncytial virus (rsv) is a transcription processivity factor that is essential for virus replication. the function of rsv m2-1 protein can be examined by using an rsvlacz minigenome assay in vitro since the expression of the lacz gene is dependent on m2-1. the m2-1 protein of pneumonia virus of mice (pvm), also a member of the pneumovirus genus, functions poorly in the rsvlacz minigenome assay despite conservation of the cys(3)-his(1) motif at its n terminus and a ...200312692207
inhibition of respiratory syncytial virus fusion by the small molecule vp-14637 via specific interactions with f protein.human respiratory syncytial virus (rsv) is a major cause of respiratory tract infections worldwide. several novel small-molecule inhibitors of rsv have been identified, but they are still in preclinical or early clinical evaluation. one such inhibitor is a recently discovered triphenol-based molecule, vp-14637 (viropharma). initial experiments suggested that vp-14637 acted early and might be an rsv fusion inhibitor. here we present studies demonstrating that vp-14637 does not block rsv adsorptio ...200312692208
low mortality rates related to respiratory virus infections after bone marrow transplantation.respiratory viruses (rvs) frequently cause severe respiratory disease in bone marrrow transplant (bmt) recipients. to evaluate the frequency of rv, nasal washes were collected year-round from bmt recipients with symptoms of upper respiratory tract infection (uri). direct immunofluorescence assay was performed for respiratory syncytial virus (rsv), influenza (flu) a and b, adenovirus and parainfluenza (paraflu) virus. patients with rsv pneumonia or with upper rsv infection, but considered at high ...200312692610
antibody-dependent enhancement, a possible mechanism in augmented pulmonary disease of respiratory syncytial virus in the bonnet monkey model.bonnet monkeys develop an enhanced disease after immunization with the formalin-inactivated (fi) respiratory syncytial virus (rsv) vaccine that is characterized by increased viral replication in perivascular sites of the lung. these sites contain many mononuclear cells, which are known to be permissive for rsv replication. to test the hypothesis that fi-rsv vaccine stimulates the production of enhancing antibodies that serve to increase the replication of rsv in macrophages, in vitro studies wer ...200312696005
immune responses to the nonglycosylated ectodomain of respiratory syncytial virus attachment glycoprotein mediate pulmonary eosinophilia in inbred strains of mice with different mhc haplotypes.development of subunit vaccines against respiratory syncytial virus (rsv) for naive human infants is hindered by concerns that immunization with the fusion or attachment (g) proteins will elicit polarized type 2 t cell responses and cause immunopotentiation upon subsequent natural infection. we investigated the regions of g protein responsible for inducing a type 2 t cell phenotype in inbred mice of different mhc haplotype toward development of vaccines with improved safety. as demonstrated by i ...200312696122
moderate local and systemic respiratory syncytial virus-specific t-cell responses upon mild or subclinical rsv infection.respiratory syncytial virus (rsv) infections are a major cause of severe respiratory disease in infants. it has been shown that there is an increased frequency of childhood wheezing in ex-bronchiolitic preteen children. this was postulated to be mediated by a vigorous virus-specific th2 response influencing the further development of the immune system. little is known about the possible role of the immune response to clinically mild rsv infections in this respect. we have studied the rsv-specifi ...200312696123
gene therapy with inducible nitric oxide synthase protects against myocardial infarction via a cyclooxygenase-2-dependent mechanism.although the inducible isoform of no synthase (inos) mediates late preconditioning (pc), it is unknown whether inos gene transfer can replicate the cardioprotective effects of late pc, and the role of this protein in myocardial ischemia is controversial. thus, the cdna for human inos was cloned behind the rous sarcoma virus (rsv) promoter to create adenovirus (ad) 5/inos lacking e1, e2a, and e3 regions. intramyocardial injection of ad5/inos in mice increased local inos protein expression and act ...200312702642
epidemiology of respiratory syncytial virus bronchiolitis in hospitalized infants in greece.new therapies have been introduced for the prophylaxis and treatment of respiratory syncytial virus (rsv) infection in recent years. the aim of the study was to determine the epidemiological and clinical characteristics of infants hospitalized with bronchiolitis in our area. all patients under 1 year of age admitted with acute bronchiolitis during four consecutive rsv seasons from february 1, 1997 to june 30, 2000 were enrolled in the study. the records of patients admitted during the first seas ...200312705624
respiratory syncytial virus decreases the capacity of myeloid dendritic cells to induce interferon-gamma in naïve t cells.respiratory syncytial virus (rsv) is the most common cause of bronchiolitis in infants under 6 months of age. since an rsv infection does not necessarily prevent a reinfection, we asked whether rsv might subvert an effective immune response by interfering with the function of dendritic cells (dcs). immature dcs cultured from cord blood stem cells and infected with rsv reduced the rate of interferon-gamma (ifn-gamma) production in co-cultured autologous naïve t cells stimulated with the superanti ...200312709017
rehospitalization for respiratory syncytial virus infection in infants with extremely low gestational age or birthweight in denmark.to determine the risk of rehospitalization for respiratory syncytial virus (rsv) infection during the first 2 y of life in extremely preterm infants.200312710653
infection efficiency of human and mouse embryonic stem cells using adenoviral and adeno-associated viral vectors.human and mouse embryonic stem (es) cells have the capacity to differentiate into derivatives of all three germ layers, suggesting novel therapies for degenerative, metabolic, and traumatic disorders. es-based regenerative medicine will be further advanced by the development of reliable methods for transgene introduction and expression. here, we show infection of human and mouse embryonic stem (es) cells with two of the most popular vectors in gene transfer, adenovirus type 5 (ad5) and adeno-ass ...200312713701
the quest for an efficacious antiviral for respiratory syncytial virus.respiratory syncytial virus (rsv) continues as an emerging infectious disease not only among infants and children, but also for the immune-suppressed, hospitalized and the elderly. to date, ribavirin (virazole) remains the only therapeutic agent approved for the treatment of rsv. the prophylactic administration of palivizumab is problematic and costly. the quest for an efficacious rsv antiviral has produced a greater understanding of the viral fusion process, a new hypothesis for the mechanism o ...200212718405
ribavirin treatment up-regulates antiviral gene expression via the interferon-stimulated response element in respiratory syncytial virus-infected epithelial cells.respiratory syncytial virus (rsv) is a mucosa-restricted virus that is a leading cause of epidemic respiratory tract infections in children. rsv replication is a potent activator of the epithelial-cell genomic response, influencing the expression of a spectrum of cellular pathways, including proinflammatory chemokines of the cc, cxc, and cx(3)c subclasses. ribavirin (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a nontoxic antiviral agent currently licensed for the treatment of severe ...200312719586
adenovirus-mediated gene transfer of enhanced herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing.the herpes simplex virus 1 (hsv) thymidine kinase (tk) suicide gene together with ganciclovir (gcv) have been successfully used for the in vivo treatment of various solid tumors and for the ablation of unwanted transfused stem cells in recent clinical trials. with the aim of improving this therapeutic system, we compared the potential efficacy of adenoviral (ad) vectors expressing enhanced tk mutants in vitro and in vivo. the previously created hsv-tk mutants dm30 and sr39, created by random seq ...200312719705
the complex relationship between respiratory syncytial virus and allergy in lung disease.epidemiologic studies suggest a strong link between severe respiratory syncytial virus (rsv)-induced bronchiolitis in infancy and allergic disease; however, the mechanisms determining this relationship are currently unknown. in this review article, we summarize data from human clinical studies that explore the association between rsv infection and allergy, some that suggest that rsv bronchiolitis requiring hospitalization leads to an increased incidence of the allergic phenotype and others that ...200312725686
respiratory syncytial virus in healthy adults: the cost of a cold.respiratory syncytial virus (rsv) is well recognized as a major pathogen of lower respiratory tract infection and hospitalization in young infants. more recently the pathogenicity of rsv has been demonstrated in elderly adults, institutionalized individuals, and those with compromised immune function. in these populations rsv spreads with ease and frequently results in severe or fatal cardiopulmonary complications. in younger, healthy adults, however, the manifestations and importance of rsv inf ...200312727524
rsv molecular characterization and specific antibody response in young children with acute lower respiratory infection.the presence of respiratory syncytial virus (rsv) in nasopharyngeal aspirates (npa) were studied in 254 hospitalized argentinean children with acute lower respiratory infection tract (alri). the specific humoral immune response and partial sequences of the g protein gene were studied in a subset of 22 children with rsv confirmed infection. the rsv igm detection and the rsv igg titration were made by immunofluorescence assay (ifa) in pairs of sera. the partial rsv g gene sequences were obtained b ...200312727528
dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus.a study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (rsv-lrti).200312728156
optimized detection of respiratory viruses in nasopharyngeal secretions.nasopharyngeal secretions (nps) from 121 (110 pediatric) patients with acute respiratory infections were examined for respiratory virus detection by: i) conventional virus isolation in cell cultures (cc) using hep-2, llc-mk2, and mdck cells; ii) rapid virus isolation using shell vial cultures (svc) of a mixture (mix) of mink lung epithelial cells (mv1lu) and human lung carcinoma (a549) cells in comparison to llc-mk2 and mdck cells; iii) direct fluorescent antibody (dfa) assay on nps cells. a poo ...200312737194
differential expression of ifn-alpha subtypes in human pbmc: evaluation of novel real-time pcr assays.studies of the human ifn-alpha subtype system have been hampered by the lack of efficient procedures to quantify and differentiate the expression of the highly homologous ifn-alpha subtypes. here we evaluate four novel real-time pcr assays for the specific detection and quantification of ifn-alpha mrna for the subtypes alpha(2), alpha(6), alpha(8) and alpha(1/13) in a combined assay in human peripheral blood mononuclear cells (pbmc). this included (a) the selection of beta-glucuronidase (gus) as ...200312738374
profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus.actin is required for the gene expression and morphogenesis of respiratory syncytial virus (rsv), a clinically important pneumovirus of the paramyxoviridae family. in hep-2 cells, rsv infection also induces actin stress fibers, which may be important in the immunopathology of the rsv disease. profilin, a major regulator of actin polymerization, stimulates viral transcription in vitro. thus, we tested the role of profilin in rsv growth and rsv-actin interactions in cultured cells (ex vivo).200312740026
activation of vascular endothelial cells by il-1alpha released by epithelial cells infected with respiratory syncytial virus.although pulmonary inflammation is a serious, sometimes life-threatening, consequence of respiratory syncytial virus (rsv) infection, the mechanisms involved are not well understood. since the process of inflammation is initiated by a complex series of events including the activation of specific adhesion molecules on vascular endothelium, we searched for endothelial cell-activating factors released from rsv-infected epithelial cells. we demonstrate here that vascular endothelial cells exposed to ...200312742380
the compound datem inhibits respiratory syncytial virus fusion activity with epithelial cells.the effect of diacetyltartaric acid esters of mono and diglycerides (datem) on fusion of respiratory syncytial virus (rsv) with hep-2 cells was studied using the r18 fluorescence dequenching fusion assay. at datem concentrations less than 2.0 microg/ml, the inhibition of fusion increased with the concentration of datem. at 2 microg/ml of datem, the fusion was suppressed by 80-90%. studies examining possible mechanism of fusion-inhibition indicated that datem was likely adsorbed onto lipid membra ...200312742571
molecular and genetic determinants of rous sarcoma virus integrase for concerted dna integration.site-directed mutagenesis of recombinant rous sarcoma virus (rsv) integrase (in) allowed us to gain insights into the protein-protein and protein-dna interactions involved in reconstituted in-viral dna complexes capable of efficient concerted dna integration (termed full-site). at 4 nm in, wild-type (wt) rsv in incorporates approximately 30% of the input donor into full-site integration products after 10 min of incubation at 37 degrees c, which is equivalent to isolated retrovirus preintegration ...200312743305
the g glycoprotein of respiratory syncytial virus depresses respiratory rates through the cx3c motif and substance p.respiratory syncytial virus (rsv) infection in the neonate can alter respiratory rates, i.e., lead to episodes of apnea. we show that rsv g glycoprotein reduces respiratory rates associated with the induction of substance p (sp) and g glycoprotein-cx3cr1 interaction, an effect that is inhibited by treatment with anti-g glycoprotein, anti-sp, or anti-cx3cr1 monoclonal antibodies. these data suggest new approaches for treating some aspects of rsv disease.200312743318
plasma endothelin-1 in infants and young children with acute bronchiolitis and viral pneumonia.respiratory syncytial virus (rsv) infections that occur during the first three years of life have been demonstrated to be associated with the development of childhood asthma. the mechanism of virus-triggered airway inflammation is not fully understood. endothelin-1 is a potent bronchoconstrictor involved in many diseases including respiratory tract infections. infants and young children diagnosed with either viral pneumonia or acute bronchiolitis, their age ranging between 2 months and 3 years, ...200212744623
immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: a multi-center trial in children with cystic fibrosis.a third generation, purified fusion protein (pfp-3) vaccine was developed to prevent severe respiratory syncytial virus (rsv) disease in high-risk groups. a phase ii, multi-center, adjuvant-controlled trial was performed in rsv seropositive children with cystic fibrosis (cf); 151 received the adjuvant-control and 143 received the vaccine. details of the vaccine-induced immune response are presented. at enrollment, rsv-specific, serum antibodies were comparable between both groups. a highly sensi ...200312744878
a single amino acid substitution in a recombinant g protein vaccine drastically curtails protective immunity against respiratory syncytial virus (rsv).recent studies have indicated a dominant t cell epitope located approximately between amino acids 184 and 203 on the respiratory syncytial virus (rsv) g protein. using an escherichia coli-grown plasmid vector encoding a fragment of thioredoxin (trx) fused to a central region (amino acids 128-229) of the rsv g protein, we employed site-directed mutagenesis to investigate the importance of selected amino acids on vaccine efficacy. by changing two amino acids arg 188 and lys 192 to alanine, the abi ...200312744884
enhanced pulmonary immunopathology following neonatal priming with formalin-inactivated respiratory syncytial virus but not with the bbg2na vaccine candidate.prevention of respiratory syncytial virus (rsv) disease will implicate neonatal priming. however, neonatal antigen exposure frequently results into th2-like responses, some of which are critical for formalin-inactivated rsv (fi-rsv)-associated lung immunopathology. neonatal immunization of mice may thus represent a more stringent model of rsv-enhanced pathology than adults. indeed, after rsv challenge, lung cell infiltration, lymphocyte activation, and eosinophilia were higher following neonatal ...200312744902
[respiratory syncytial infections in the elderly. seven cases and review of the literature].we report 7 cases of respiratory syncytial virus (rsv) infections among elderly patients hospitalized for acute lower tract infection during the winter months. the median age was 95 years (range: 79-106 years). 6 patients were living in nursing homes. all patients had chronic cardiopulmonary conditions. clinical symptoms included upper respiratory tract symptoms for 3 of them and lower respiratory tract symptoms for all of them. three patients developed a severe infection with acute respiratory ...200312746643
palivizumab prophylaxis of respiratory syncytial virus disease in 2000-2001: results from the palivizumab outcomes registry.the objective of the registry was to characterize the population of infants receiving prophylaxis for respiratory syncytial virus (rsv) disease by describing the patterns and scope of usage of palivizumab in a cross section of us infants. rsv hospitalization outcomes were also described. the palivizumab (synagis, medimmune, inc., 25 west watkins mill road, gaithersburg, md 20878) outcomes registry was a prospective multicenter survey conducted at 63 sites. demographics, injection history, and rs ...200312746948
effect of an educational program on the treatment of rsv lower-respiratory-tract infection.the effectiveness and outcomes of an educational program to decrease ribavirin and antimicrobial prescribing rates and associated costs for patients with respiratory syncytial virus (rsv) lower-respiratory-tract infection are described. an educational program on the appropriate treatment for rsv infections was conducted for attending physicians and medical residents with multiple methods and forums during the 1994-95 rsv season. a retrospective chart review of 2396 patients admitted to a pediatr ...200312749162
zileuton reduces respiratory illness and lung inflammation, during respiratory syncytial virus infection, in mice.to determine the role of leukotrienes in a mouse model of respiratory syncytial virus (rsv) infection, we correlated the quantity of leukotrienes in lung lavage fluids of infected mice with respiratory rates and measures of outflow obstruction and then determined the effects of the leukotriene inhibitor zileuton on clinical features and lung function. concentrations of leukotrienes were correlated with both increasing respiratory rates and the degree of prolongation of expiratory time. administr ...200312751035
initiation factor eif2b not p70 s6 kinase is involved in the activation of the pi-3k signalling pathway induced by the v-src oncogene.our data show that in hamster fibroblasts transformed by rous sarcoma virus (rsv), the phosphoinositide 3'-kinase (pi-3k)/akt/glycogen synthase kinase 3 antiapoptotic pathway is upregulated and involved in increased protein synthesis through activation of initiation factor eif2b. upon inhibition of pi-3k by wortmannin, phosphorylation of 70-kda ribosomal protein s6 kinase (p70 s6k) and its physiological substrate, ribosomal protein s6, decreased in the non-transformed cells but not in rsv-transf ...200312753910
risk factors for hypoxemia and respiratory failure in respiratory syncytial virus bronchiolitis.respiratory syncytial virus (rsv) bronchiolitis is a common infection in young children and may result in hospitalization. we examined the incidence of, and risk factors associated with, hypoxemia and respiratory failure in 216 children aged < 24 months admitted consecutively for proven rsv bronchiolitis. hypoxemia was defined as spo2 < 90% in room air and severe rsv bronchiolitis requiring intubation and ventilation was categorized as respiratory failure. corrected age at admission was used for ...200212757230
influenza- and respiratory syncytial virus-associated morbidity and mortality in the nursing home population.to estimate winter viral-related morbidity and mortality in tennessee nursing home residents during 4 consecutive years.200312757561
immunology of viral respiratory tract infection in infancy.respiratory viruses such as respiratory syncytial virus (rsv), parainfluenza viruses (piv) and the influenza viruses cause severe lower respiratory tract disease in infants and children throughout the world. we discuss the recent discovery of the epidemiologic importance of the human metapneumoviruses, first reported in 2001. experimental live-attenuated vaccines for each of these viruses are being developed for intranasal administration in the first weeks or months of life. the immunology of th ...200312758048
[molecular epidemiology of respiratory syncytial virus infection in infants].to search for the molecular epidemiology of respiratory syncytial virus (rsv) infection in infants.199912759984
interaction between respiratory syncytial virus and particulate matter in guinea pig alveolar macrophages.alveolar macrophages (am) play a pivotal role in host lung defense mechanisms. respiratory syncytial virus (rsv) stimulates secretion of proinflammatory cytokines in am while it suppresses the cell's phagocytic ability. however, exposure of am to ambient particulate matter (pm10) has been reported to inhibit rsv uptake. the mechanisms involved in the interaction between rsv and pm10 in am are not known. we hypothesize that the cellular response of am to rsv and pm10 is dependent on the sequence ...200312760967
virology of infantile chronic recurrent parotitis in santiago de chile.infantile chronic recurrent parotitis (icrp) has been attributed to multiple causes, including viral infections, and therefore its treatment remains empirical. our aim was to evaluate the involvement of respiratory and oropharyngeal viruses in acute episodes of icrp. seventy children were studied, 50 patients and 20 age-matched controls, in a 2-year follow-up study. saliva samples were taken from the parotid duct and analyzed by viral isolation and immunofluorescence for adenovirus (ad), respira ...200312767011
detection of human respiratory syncytial virus sequences in peripheral blood mononuclear cells.peripheral blood mononuclear cells (pbmc) obtained from patients with lower respiratory infections were examined for the detection of human respiratory syncytial virus (rsv) sequences in the n region using the reverse transcription polymerase chain reaction (rt-pcr). rsv infection was confirmed by at least one method, i.e., virus isolation, enzyme immunoassay for viral antigen, and rt-pcr of nasopharyngeal secretions (nps) samples. the detection rate for rsv rna in pbmc obtained from rsv-infecte ...200312767015
broad spectrum anti-rna virus activities of titanium and vanadium substituted polyoxotungstates.seven polyoxotungstates substituted with vanadium or titanium atoms were examined for their activity against flaviviridae (dengue fever virus, dfv), orthomyxoviridae (influenza virus type a, fluv-a), paramyxoviridae (respiratory syncytial virus, rsv, parainfluenza virus type 2, pfluv-2 and canine distemper virus, cdv) and lentiviridae (human immunodeficiency virus type 1, hiv-1) families. among the seven polyoxotungstates examined, pm-43 [k(5)[sivw(11)o(40)]], pm-47 [k(7)[bvw(11)o(40)]], and pm- ...200312767474
complementary approaches to understanding the role of proteases and their natural inhibitors in neoplastic development: retrospect and prospect.a great deal of evidence has accumulated in recent years for an important but complex role for proteases in tumor development. however, attempts to treat cancer in humans with anti-proteases have been disappointing, and it has been suggested that more basic groundwork is needed before anti-proteases can be effectively applied. considerable basic information comes from the recognition that earlier results on transformation of chicken embryo fibroblasts (cef) by the bryan strain of rous sarcoma vi ...200312771023
type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis.we examined the in vivo immune response of infants to natural respiratory syncytial virus (rsv) infection through analysis of cytokine levels in nasal lavage fluid and stimulated peripheral blood mononuclear cells. eighty-eight babies with at least one parent with atopy and asthma were prospectively studied through their first winter. twenty-eight infants had an upper respiratory tract infection where rsv was detected, of whom nine developed signs of acute bronchiolitis. nasal lavage specimens w ...200312773328
respiratory syncytial virus-induced ccl5/rantes contributes to exacerbation of allergic airway inflammation.severe respiratory syncytial virus (rsv) infection has a significant impact on airway function and may induce or exacerbate the response to a subsequent allergic challenge. in a murine model combining early rsv infection with later cockroach allergen (cra) challenge, we examined the role of rsv-induced ccl5/rantes production on allergic airway responses. rsv infection increased ccl5 mrna and protein levels, peaking at days 8 and 12, respectively. administration of ccl5 antiserum during days 0-14 ...200312778486
multicenter, randomized, controlled study of porcine surfactant in severe respiratory syncytial virus-induced respiratory failure.objective: recently, natural exogenous surfactant replacement has been used in experimental models and clinical trials for the treatment of severe respiratory syncytial virus (rsv) disease. the present study was aimed at verifying this hypothesis and confirming the results of our previous pilot study by assessing the effect of surfactant treatment in mechanically ventilated infants with severe rsv-induced respiratory failure. design: multicenter, randomized, controlled study. setting: six pediat ...200212780967
effects of interleukin-18 on asthmatic airway inflammation and nuclear factor kappa-b in murine models.to investigate the effects of interleukin-18 (il-18) on asthmatic airway inflammation and nuclear factor kappa-b (nf-kappab) in a murine asthmatic model.200312781029
specific in vitro cleavage of mason-pfizer monkey virus capsid protein: evidence for a potential role of retroviral protease in early stages of infection.processing of gag polyproteins by viral protease (pr) leads to reorganization of immature retroviral particles and formation of a ribonucleoprotein core. in some retroviruses, such as hiv and rsv, cleavage of a spacer peptide separating capsid and nucleocapsid proteins is essential for the core formation. we show here that no similar spacer peptide is present in the capsid-nucleocapsid (ca-nc) region of mason-pfizer monkey virus (m-pmv) and that the ca protein is cleaved in vitro by the pr withi ...200312781718
synthesis, refolding and protective immune responses of a potential antigen for human respiratory syncytial virus vaccine.the design of new antigens with both high immunogenic and safety properties is of particular interest to vaccine against infectious diseases. in the present study, we describe the synthesis and the refolding of peptide g20 derived from the human respiratory syncytial virus (hrsv) g-protein. g20 (mef g140-190 g144-158) is a peptide of 69 amino acids with two disulfide bridges, which comprises multiple protective b-cell epitopes. it was deleted of the t helper cell epitope 184-198 of the rsv g-pro ...200312787448
role of respiratory viruses in children with acute otitis media.the role of viral infection in acute otitis media (aom) has not been fully elucidated. we determined the presence of various respiratory viruses in middle ear fluid (mef) specimens from children with aom in order to determine whether viral infection or combined effects of viral and bacterial infection enhance or prolong the inflammation in the middle ear, thus worsening clinical outcome.200312791457
genetic variability among group a and b respiratory syncytial virus isolates from a large referral hospital in new delhi, india.respiratory syncytial virus (rsv) is an important childhood pathogen of acute lower respiratory infections in developed and developing countries. the molecular epidemiology of rsv in india is largely unknown. the present study was undertaken to standardize and evaluate reverse transcription-pcr (rt-pcr) for the rapid and simultaneous detection of rsv groups a and b in clinical samples and to study intragroup genetic variability. rt-pcr was evaluated by comparing the results of seminested rt-pcr ...200312791842
respiratory syncytial virus infections in the pediatric intensive care unit: clinical characteristics and risk factors for adverse outcomes.to describe the clinical characteristics of infants admitted to a pediatric intensive care unit (picu) with respiratory syncytial virus (rsv) infection, including the prevalence of indications for rsv passive antibody prophylaxis (as currently recommended by the american academy of pediatrics), and to identify risk factors that predict adverse outcomes among this population.200112793934
mechanical ventilatory support in infants with respiratory syncytial virus infection.objective: to present a review of current knowledge of the use of mechanical ventilatory support in the management of infants with respiratory failure secondary to infection with respiratory syncytial virus (rsv). data sources: medline and manual search for case reports and clinical trials that address management strategies for respiratory support of infants with rsv infection. data extraction and synthesis: critical appraisal of reported epidemiologic and clinical data regarding risk factors, p ...200112793941
evaluation of a quantitative real-time pcr for the detection of respiratory syncytial virus in pulmonary diseases.respiratory syncytial virus (rsv) is known to cause acute lower respiratory tract infections (ari) in young children and is involved in exacerbation of chronic obstructive pulmonary disease (copd) in adults. the role of rsv in stable copd and the viral load in different respiratory diseases has not been investigated to date. the present authors established and evaluated a quantitative taqman real-time polymerase chain reaction assay specific for rsv subgroup a. absolute quantification for the de ...200312797486
cd40 ligand (cd154) improves the durability of respiratory syncytial virus dna vaccination in balb/c mice.respiratory syncytial virus (rsv) infection is the single most important cause of serious acute respiratory illness in children <1 year of age worldwide, and is associated with life-threatening pneumonia or bronchiolitis in the elderly. current vaccine strategies include live, attenuated virus, subunit and dna vaccines, however, none have been sufficiently safe, or shown to induce satisfactory long-term immunity, thus immune modulators are being considered to enhance the effectiveness of rsv vac ...200312798640
impact of palivizumab prophylaxis on respiratory syncytial virus hospitalizations in high risk alaska native infants.alaska native children experience extremely high rates of hospitalization for respiratory syncytial virus (rsv) infection. we evaluated the effect of palivizumab prophylaxis on the incidence of rsv hospitalizations in high risk alaska native children.200312799511
incidence of hyponatraemia and hyponatraemic seizures in severe respiratory syncytial virus bronchiolitis.to document the incidence and early evolution of hyponatraemia (serum sodium < 136 mmol l(-1)) associated with respiratory syncytial virus (rsv) bronchiolitis in infants requiring intensive care.200312801108
cost of hospitalization for respiratory syncytial virus chest infection and implications for passive immunization strategies in a developing nation.respiratory syncytial virus (rsv) chest infection is a common cause of hospitalization in the very young child. the aim of this study was to determine the direct cost of resource utilization in the treatment of children hospitalized with rsv chest infection and the potential cost-savings with passive immunization for high-risk infants. an audit of the hospital resource consumption and its costs was performed for 216 children aged < 24 mo admitted with rsv chest infection between 1995 and 1997. t ...200312801117
non-hiv antivirals - a review of the recent patent literature.this review covers the non-hiv antiviral patent literature from december 2001 to april 2002. most of the patent applications describe new compounds for the treatment of hepatitis c virus (hcv) by inhibition of the ns3 serine protease. several examples of both nucleoside and non-nucleoside inhibitors of the hcv polymerase ns5b have been reported. hepatitis b virus (hbv) therapy continues to be dominated by nucleoside analogs, but several non-nucleoside hbv polymerase inhibitors have also been rep ...200212802698
role of monocytes and eosinophils in human respiratory syncytial virus infection in vitro.rsv infection in airway epithelial cells (ec) results in production of the chemokines rantes and mip1alpha and the leukocyte differentiation factor gm-csf. the chemokines attract monocytes and eosinophils to the site of infection, where gm-csf may influence their function and differentiation. in turn, these inflammatory cells may limit the progression of rsv infection, as well as initiate immune responses. in the present study, the effect of monocytes and eosinophils on viral replication and inf ...200312804531
respiratory syncytial virus infection activates stat signaling in human epithelial cells.acute respiratory syncytial virus (rsv) infection causes airway inflammation and exacerbates asthma, but the mechanism of inflammation is poorly understood. the role of the stat-signaling pathway in rsv infection in epithelial cells was examined in this study. dna microarray analyses of rsv-infected human alveolar type ii (a549) epithelial cells identified several genes whose expression was altered from -5.5 to +56.4-fold. four of the highly expressed genes contained stat-binding elements. in a5 ...200312804610
three-dimensional structure of the m-mulv ca protein on a lipid monolayer: a general model for retroviral capsid assembly.although retroviruses from different genera form morphologically distinct capsids, we have proposed that all of these structures are composed of similar hexameric arrays of capsid (ca) protein subunits and that their distinct morphologies reflect different distributions of pentameric declinations that allow the structures to close. consistent with this model, ca proteins from both hiv-1 and rous sarcoma virus (rsv) form similar hexagonal lattices. however, recent structural studies have suggeste ...200312805204
respiratory syncytial virus nucleoprotein-specific cytotoxic t-cell epitopes in a south african population of diverse hla types are conserved in circulating field strains.this study identifies memory cytotoxic t lymphocyte (ctl) epitopes to respiratory syncytial virus (rsv) in healthy south african adults and demonstrates the conservation of those epitopes in circulating field strains of rsv in south africa. thirty-seven healthy adults from a population with diverse hla backgrounds were screened by gamma interferon (ifn-gamma) enzyme-linked immunospot for memory ctl activity in response to overlapping peptides representing the complete nucleoprotein (n) of rsv. r ...200312805430
risk factors for admission and the role of respiratory syncytial virus-specific cytotoxic t-lymphocyte responses in children with acute bronchiolitis.risk factors for admission of children with acute bronchiolitis have remained controversial. technological advances in the measurements of cytotoxic t-lymphocyte (ctl) activity, enable respiratory syncytial virus (rsv)-specific ctl activity to be studied in infants with bronchiolitis for the first time. we evaluated risk factors for admission of children with acute bronchiolitis and determined the role of ctl responses in those infected with rsv.200312806723
growth of respiratory syncytial virus in mink lung epithelial cells.mink lung epithelial cells (mv-1-lu) were tested for their ability to support the growth and serial passage of respiratory syncytial virus (rsv) in vitro. indian isolates of rsv induced distinctive cytopathic effect with typical rounding of cells followed by detachment with more than 50 per cent cells showing bright fluorescence using anti-rsv monoclonal antibodies in immunofluorescence test. serial passage of rsv was possible in mv-1-lu cells without loss of sensitivity of the cells for virus g ...200212807152
comparative viral frequency in mexican children under 5 years of age with and without upper respiratory symptoms.in mexico, there is a lack of up-to-date published data that show viruses to be the main cause of acute respiratory infection (ari). the objective of this study was to estimate the comparative viral frequency between children under the age of 5 years with and without ari (n = 179 in each group) in a suburban community (nezahualcóyotl city). a nasopharyngeal sample was collected for viral culture and identification was carried out by indirect immunofluorescence (iif) using mabs. there were no sex ...200312808080
"bystander" recruitment of systemic memory t cells delays the immune response to respiratory virus infection.the concept of heterologous t cell immunity postulates that nonspecific memory t cells recruited and reactivated in the context of an unrelated virus infection may contribute to protective antiviral immunity. pulmonary infection with respiratory syncytial virus (rsv) of mice immune to lymphocytic choriomeningitis virus (lcmv) leads to substantial recruitment of systemic lcmv-specific memory cd8 t cells to the lung. using a sensitive tcr-transgenic model, we show that such "bystander" recruitment ...200312811844
myocardial injury in children with respiratory syncytial virus infection.respiratory syncytial virus (rsv) infection is associated with a number of extrapulmonary manifestations, including a sepsis-like syndrome characterized by any combination of hypothermia, fever, apnea, hypovolemia, and myocardial dysfunction. we hypothesized that rsv can have a direct injurious effect on the myocardium of infants and children that can be detected by the presence of cardiac troponin i (ctni), a highly sensitive and specific marker of myocardial injury, in the blood of patients in ...200012813266
respiratory viral infections after bone marrow/peripheral stem-cell transplantation: the christie hospital experience.respiratory virus infections are an important cause of morbidity and mortality in bone marrow transplant patients. a retrospective study was performed on the bone marrow transplant unit at the christie hospital manchester. the aim of this study was to determine the frequency, clinical presentation, laboratory diagnosis, types of intervention (eg antiviral agents used) and the outcome of such infections in this cohort of transplant recipients. data were collected from a total of 626 adult patient ...200312815481
surveillance for respiratory illness in long-term care settings: detection of illness using a prospective research technique.the overall frequency and severity of viral respiratory infections affecting residents of long-term care facilities (ltcfs) is not well described. this is due primarily to the cumbersome and expensive techniques required for adequate surveillance of respiratory illnesses and the associated costs and availability of a laboratory capable of the relevant and timely report of diagnostic tests. here we describe our technique for surveillance of respiratory illness in the ltcf. elements of it may serv ...200012818025
rational promoter selection for gene transfer into cardiac cells.cardiomyocytes (cmcs) are extremely difficult to transfect with non-viral techniques, but they are efficiently infected by adenoviruses. the most commonly used promoters to drive protein expression in cardiac myocytes are of viral origin, since they are believed to be constitutively active and minimally regulated by physiological or pharmacological challenge of cells. in recombinant adenoviruses, we systematically compared three different promoters: the cytomegalovirus (cmv), the rous sarcoma vi ...200312818573
inhalation efficacy of rfi-641 in an african green monkey model of rsv infection.human respiratory syncytial virus (rsv) is a major cause of acute upper and lower respiratory tract infections. rfi-641 is a novel rsv fusion inhibitor with potent in vitro activity. in vivo efficacy of rfi was determined in an african green monkey model of rsv infection involving prophylactic and therapeutic administration by inhalation exposure. inhalation was with an rfi-641 nebulizer reservoir concentration of 15 mg/ml for 15 minutes (short exposure) or 2 hours (long exposure). efficacy and ...200312823630
the matrix protein of human respiratory syncytial virus localises to the nucleus of infected cells and inhibits transcription.we studied the kinetics of localisation of matrix (m) protein of human respiratory syncytial virus (rsv) in infected cells. m protein was detected in the nucleus early in infection, by confocal microscopy and by immunoblotting of nuclear fractions. we next tested the possibility that m protein may be involved in inhibition of host cell transcription. nuclear extracts from rsv infected cells had less transcriptional activity in vitro when compared to nuclear extracts from mock infected cells. in ...200312827470
respiratory syncytial virus associated illness in high-risk children and national characterisation of the circulating virus genotype in south africa.there is limited information about respiratory syncytial virus (rsv) in high-risk children from developing countries or on the genotype characterisation of the circulating virus.200312829040
an outbreak of respiratory syncytial virus infection in a bone marrow transplant unit: effect on engraftment and outcome of pneumonia without specific antiviral treatment.immunocompromised haematological patients are at high risk for severe, often fatal, respiratory syncytial virus (rsv) pneumonia. in the 2001 winter season, 16 of 195 (8.2%) adult haematological in-patients were diagnosed with rsv infection. eight patients had undergone stem cell transplantation. the median age was 53 years (range 20-67). a total of 11 patients had nosocomial rsv infection while the rest (five) had community-acquired infection. all patients were febrile and had upper respiratory ...200312838285
structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the f protein and a syncytium formation assay.respiratory syncytial virus (rsv) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the rsv fusion protein (rsv-f). a novel in vitro assay of recombinant rsv-f function has been devised and used to characterize a number of escape mutants for three known inhibitors of rsv-f that have been isolated. homology modeling of the rsv-f structure has been ...200312842618
high prevalence of human metapneumovirus infection in young children and genetic heterogeneity of the viral isolates.rna of the newly identified human metapneumovirus (hmpv) was detected in nasopharyngeal aspirates of 11 of 63 (17.5%) young children with respiratory tract disease. markers of infection caused by another member of the pneumovirinae subfamily of the family paramyxoviridae, respiratory syncytial virus (rsv), were identified in 15 of these patients (23.8%). three patients were simultaneously infected with hmpv and rsv. studies of the clinical characteristics of hmpv-infected children did not reveal ...200312843040
clara cell secretory protein modulates lung inflammatory and immune responses to respiratory syncytial virus infection.clara cell secretory protein (ccsp) has been shown to have anti-inflammatory and immunomodulatory functions in the lung. respiratory syncytial virus (rsv) is the most common cause of respiratory infection in infants and young children. rsv usually infects small airways and likely interacts with the clara cells of bronchioles. to determine a possible role for ccsp during acute rsv infection, ccsp-deficient (ccsp(-/-)) and wild-type (wt) mice were intratracheally infected with rsv and the lung inf ...200312847279
bronchoalveolar lavage cytokine profiles in acute asthma and acute bronchiolitis.the pathogenetic basis for the relationship between acute bronchiolitis and asthma has not yet been completely elucidated.200312847481
safety and immunogenicity of respiratory syncytial virus purified fusion protein-2 vaccine in pregnant women.a randomized, double-blind, placebo controlled study was carried out to determine the safety and immunogenicity of rsv pfp-2 vaccine (wyeth-lederle vaccines, ny) in 35 healthy women in the third trimester of pregnancy and their offspring. infants were followed during their first rsv season for occurrence and severity of respiratory illnesses. rsv-pfp-2 vaccine was safe and well tolerated by pregnant women. mild pain at the site of injection occurred in 65% of pfp-2 and 13% of placebo recipients ...200312850361
correlates of immunity to respiratory syncytial virus (rsv) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies.to determine if respiratory syncytial virus (rsv) specific, serum antibody titers correlate with protection against rsv associated-hospitalization at all ages.200312850364
winter respiratory viruses and health care use: a population-based study in the northwest united states.to quantify health care use among adults during influenza and respiratory syncytial virus (rsv) seasons, we identified a cohort of veterans aged >or=18 years who used department of veterans affairs (va) facilities in oregon and washington states as their source of health care. during 1998-2000, veterans accrued 237,159 person-years of follow-up. using va data sources, we measured acute cardiopulmonary hospitalizations and primary care and urgent care visits. differences between rates of study ev ...200312856212
[respiratory syncytial virus lower respiratory tract infection: our series].the authors report 57 cases of respiratory syncytial virus (rsv) lower respiratory tract infection. the diagnosis was performed by detection of specific serum antibodies of igm class or by direct detection of rsv antigens in nasopharyngeal specimens. most of the patients were younger than one year. no one had risk factors for severe rsv infection form. all patients recovered. the authors emphasize the difficulties to discriminate between bronchiolitis and interstitial pneumonitis on the basis of ...199612858027
respiratory tract viral infections in bone marrow transplant patients.community respiratory viruses such as respiratory syncytial virus (rsv), adenovirus, influenza a, influenza b, and the parainfluenza group are frequent causes of respiratory disease in bone marrow transplant (bmt) patients.200312865800
bovine parainfluenza virus type 3 (piv3) expressing the respiratory syncytial virus (rsv) attachment and fusion proteins protects hamsters from challenge with human piv3 and rsv.parainfluenza virus type 3 (piv3) and respiratory syncytial virus (rsv) are the main causes of ubiquitous acute respiratory diseases of infancy and early childhood, causing 20-25 % of pneumonia and 45-50 % of bronchiolitis in hospitalized children. the primary goal of this study was to create an effective and safe rsv vaccine based on utilizing attenuated bovine piv3 (bpiv3) as a virus vector backbone. bpiv3 had been evaluated in human clinical trials and was shown to be attenuated and immunogen ...200312867647
establishment of respiratory syncytial virus persistence in cell lines: association with defective interfering particles.defective interfering particles (dip) have frequently been advanced to explain the persistence of virus in vitro. however, dip involvement in the establishment of respiratory syncytial virus (rsv) persistence in cell lines has not been documented. we report establishment of rsv persistence in human epithelial larynx (hep-2) and lung (h358) cell lines by infection with rsv enriched with dip. viral persistence in hep-2 and h358 has been stably maintained for >3 years without apparent cytopathic ef ...200312867758
[in vitro inhibition of respiratory syncytial virus with combined ribavirin and an oral preparation of traditional chinese medicine hu fei].to study the in vitro antiviral effect of ribavirin combined with an oral preparation of traditional chinese medicine "hu fei" (protecting the lung) on respiratory syncytial virus (rsv).200312870007
differences in participation of innate and adaptive immunity to respiratory syncytial virus in adults and neonates.innate and adaptive immune responses to respiratory syncytial virus (rsv) in neonates were assessed by cord blood mononuclear cell (mc) cytokine expression and proliferation and these responses were compared with those from adult peripheral blood mcs. in adult cells, inactivated and live virus invoked cytokines reflecting both innate and adaptive immunity (interleukin [il]-6, interferon [ifn]-gamma, il-2, tumor necrosis factor [tnf]-alpha, and il-10). low levels of il-4 were detected, although o ...200312870126
[study of a respiratory syncytial virus diagnostic test kit based on immunochromatography].we carried out clinical and basic studies of the directigen lateral flow rsv (becton, dickinson and company, usa), a rapid test kit that detects respiratory syncytial virus (hereinafter referred to as "rsv") antigens based on immunochromatography. for the clinical study, 103 nasopharyngeal aspirates from patients with acute respiratory infections were used to evaluate the kit. compared to the cell culture method, the directigen lateral flow rsv showed a sensitivity of 100% (16/16) and a specific ...200312872694
clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin.paramyxoviral infections are reported in 6% to 21% of lung transplant recipients. aerosolized ribavirin is used to treat paramyoxviral infections, but data on outcomes of this treatment in lung transplant patients are limited.200312873542
[respiratory syncytial virus infections in children in general practice].the aim of the study was to describe the course of respiratory syncytial virus (rsv) infections in children under two years of age seen in general practice.200312886566
can respiratory syncytial virus etiology be diagnosed clinically? a hospital-based case-control study in children under two years of age.an unmatched, hospital-based case-control study was performed, to determine, whether respiratory syncytial virus (rsv) etiology in hospitalized young children can be predicted clinically. children under 2 years of age admitted with a lower respiratory tract infection in three hospitals in northern germany were included (one tertiary and two secondary centers). cases were children tested positive for rsv by multiplex rt-pcr. one control group consisted of children tested negative for rsv in the m ...200312889690
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