Publications
Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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innate immune responses to influenza a h5n1: friend or foe? | avian influenza a h5n1 remains unusual in its virulence for humans. although infection of humans remains inefficient, many of those with h5n1 disease have a rapidly progressing viral pneumonia that leads to acute respiratory distress syndrome and death, but its pathogenesis remains an enigma. comparison of the virology and pathogenesis of human seasonal influenza viruses (h3n2 and h1n1) and h5n1 in patients, animal models and relevant primary human cell cultures is instructive. although the dire ... | 2009 | 19864182 |
the first swedish h1n2 swine influenza virus isolate represents an uncommon reassortant. | the european swine influenza viruses (sivs) show considerable diversity comprising different types of h1n1, h3n2, and h1n2 strains. the intensifying full genome sequencing efforts reveal further reassortants within these subtypes. here we report the identification of an uncommon reassortant variant of h1n2 subtype influenza virus isolated from a pig in a multisite herd where h1n2 swine influenza was diagnosed for the first time in sweden during the winter of 2008-2009. the majority of the europe ... | 2009 | 19863790 |
[comparison of detection sensitivity in rapid-diagnosis influenza virus kits]. | rapid-diagnosis kits able to detect influenza a and b virus by immunochromatography developed by different manufacturers, while useful in early diagnosis, may vary widely in detection sensitivity. we compared sensitivity results for eight virus-detection kits in current use--quick chaser flua, b (mizuho medy), espline influenza a & b-n (fujirebio), capilia flu a + b (nippon beckton dickinson & alfesa pharma), poctem influenza a/b (otsuka pharma & sysmex), bd flu examan (nippon beckton dickinson) ... | 2009 | 19860254 |
a novel assay for influenza virus quantification using surface plasmon resonance. | quantification of hemagglutinin (ha) by single-radial immuno diffusion (srid) is the predominant method to ensure product potency in seasonal influenza vaccines. here a new method for quantification of influenza virus using biosensor technology is presented. the method employs quantification of virus via an inhibition assay format using ha proteins for h1n1, h3n2 and b immobilized on a sensor chip. initial results showed the assay to have higher sensitivity (detection range 0.5-10 microg/ml), hi ... | 2010 | 19857452 |
alphavirus replicon particle vaccines developed for use in humans induce high levels of antibodies to influenza virus hemagglutinin in swine: proof of concept. | a propagation-defective, single-cycle, alphavirus replicon particle (rp) system was used to produce two vaccines against human influenza virus a/wyoming/03/2003 (h3n2). one vaccine was prepared from venezeulan equine encephalitis virus (veev) strain 3014 and the other from veev strain tc-83. both vaccines induced high antibody titers to the influenza hemagglutinin (ha) protein and illustrated the potential of using alphavirus rp influenza vaccines in swine. | 2010 | 19853679 |
prime-boost immunization with ha/c3d dna followed by a recombinant pseudorabies virus boost enhanced protective immunity against h3n2 swine influenza virus in mice. | dna and recombinant virus vaccines against swine influenza virus (siv) have been pursued with promising results, but induce poor immunogenicity. this study evaluated the effects of a vaccine regimen in mice including priming with three dna vaccines expressing soluble ha (sha), complete ha (tmha), or sha fused with three copies murine c3d (sha-mc3d3) and boosting with recombinant pseudorabies virus expressing ha (rprv-ha). immune responses were monitored by elisa, hi assays, and virus neutralizat ... | 2010 | 19850311 |
amantadine- and oseltamivir-resistant variants of influenza a viruses in thailand. | amantadine and oseltamivir are used to treat influenza a virus infections; however, resistance to these drugs has been widely reported throughout the world. in this study, the frequency and genetic characteristics of the drug-resistant influenza a viruses that circulated in thailand from 2006 to 2008 were investigated. the nucleotide sequences of the na and m2 genes were elucidated in order to identify mutations that confer oseltamivir- and amantadine-resistant phenotypes, respectively. a total ... | 2009 | 19850010 |
formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. | microneedle patches coated with solid-state influenza vaccine have been developed to improve vaccine efficacy and patient coverage. however, dip coating microneedles with influenza vaccine can reduce antigen activity. in this study, we sought to determine the experimental factors and mechanistic pathways by which inactivated influenza vaccine can lose activity, as well as develop and assess improved microneedle coating formulations that protect the antigen from activity loss. after coating micro ... | 2010 | 19840825 |
influenza virus ctl epitopes, remarkably conserved and remarkably variable. | virus-specific cytotoxic t lymphocytes (ctl) contribute to the control of virus infections including those caused by influenza viruses. especially under circumstances when antibodies induced by previous infection or vaccination fail to recognize and neutralize the virus adequately, ctl are important and contribute to protective immunity. during epidemic outbreaks caused by antigenic drift variants and during pandemic outbreaks of influenza, humoral immunity against influenza viruses is inadequat ... | 2009 | 19840674 |
signature peptides of influenza nucleoprotein for the typing and subtyping of the virus by high resolution mass spectrometry. | the use of high resolution mass spectrometry to record the accurate mass of signature peptides within proteolytic digests of the nucleoprotein antigen, and whole influenza virus, is shown to be able to rapidly type and subtype the virus. conserved sequences for predicted tryptic peptides were identified through alignments of those for the nucleoprotein across all influenza types and subtypes. peptides with unique theoretical masses from those generated in silico for all influenza antigen sequenc ... | 2009 | 19838412 |
sialyltransferases of marine bacteria efficiently utilize glycosphingolipid substrates. | bacterial sialyltransferases (sts) from marine sources were characterized using glycosphingolipids (gsls). bacterial sts were found to be beta-galacotoside sts. there were two types of sts: (1) st obtained from strains such as ishi-224, 05jtc1 (#1), ishi-467, 05jtd2 (#2), and faj-16, 05jte1 (#3), which form alpha2-3 sialic acid (sia) linkages, named alpha2-3st, (2) st obtained from strains such as ish-224, n1c0 (#4), pda-rec, 05jtb2 (#5), and pda-0160, 05jta2 (#6), which form alpha2-6 sia linkag ... | 2010 | 19837852 |
the effects of influenza a virus pb1-f2 protein on polymerase activity are strain specific and do not impact pathogenesis. | the influenza a virus pb1-f2 protein has been implicated as a virulence factor, but the mechanism by which it enhances pathogenicity is not understood. the pb1 gene segment of the h1n1 swine-origin influenza virus pandemic strain codes for a truncated pb1-f2 protein which terminates after 11 amino acids but could acquire the full-length form by mutation or reassortment. it is therefore important to understand the function and impact of this protein. we systematically assessed the effect that pb1 ... | 2010 | 19828614 |
transmission of pandemic h1n1 influenza virus and impact of prior exposure to seasonal strains or interferon treatment. | novel swine-origin influenza viruses of the h1n1 subtype were first detected in humans in april 2009. as of 12 august 2009, 180,000 cases had been reported globally. despite the fact that they are of the same antigenic subtype as seasonal influenza viruses circulating in humans since 1977, these viruses continue to spread and have caused the first influenza pandemic since 1968. here we show that a pandemic h1n1 strain replicates in and transmits among guinea pigs with similar efficiency to that ... | 2010 | 19828604 |
probabilistic indoor transmission modeling for influenza (sub)type viruses. | to use a probability based transmission modeling approach to examine the influenza risk of infection virus in indoor environments. this was based on 10 years of data gathered from influenza-like illness sentinel physician and laboratory surveillance, and experimental viral shedding data in taiwan. | 2010 | 19818365 |
development of a real-time rt-pcr assay for a novel influenza a (h1n1) virus. | a pandemic caused by a novel influenza a virus (h1n1) poses a serious public health threat. in this study, a real-time reverse transcriptase pcr (rt-pcr) assay based on the hemagglutinin gene was developed that discriminates the novel h1n1 from swine influenza virus, seasonal h1n1/h3n2 virus and the highly pathogenic h5n1 avian influenza virus. the sensitivity of this assay was 0.2 50% tissue culture infective dose of virus and 200 copies of in vitro-transcribed target rna. three hundred and for ... | 2010 | 19815030 |
residual immunity in older people against the influenza a(h1n1)--recent experience in northern spain. | the 2009 pandemic influenza a(h1n1) virus has a higher incidence in children and young adults, a pattern that has also been reported in seasonal influenza caused by the influenza a(h1n1)virus. we analysed age at infection in symptomatic patients with influenza in the basque country (northern spain), reported through the sentinel influenza surveillance system which monitors 2.2-2.5%of the population. between september 1999 and august 2009,influenza a(h3n2) or seasonal influenza a(h1n1) was detect ... | 2009 | 19814966 |
genetic relatedness of h6 subtype avian influenza viruses isolated from wild birds and domestic ducks in korea and their pathogenicity in animals. | we report the genetic characterization of h6 avian influenza (ai) viruses isolated from domestic ducks and wild birds in korea between april 2008 and april 2009. a phylogenetic analysis showed that the h6n1 viruses of wild birds and domestic ducks were of the same genotype (k-1) and were similar to the h6n1 virus isolated from a live poultry market in 2003, as six of the eight gene segments of those viruses had a common source. however, the h6n2 viruses of domestic poultry were separated into fo ... | 2010 | 19812266 |
detection of influenza a h1n1 and h3n2 mutations conferring resistance to oseltamivir using rolling circle amplification. | in the event of an influenza pandemic, the use of oseltamivir (otv) will undoubtedly increase and therefore it is more likely that otv-resistant influenza strains will also arise. otv-resistance genotyping using sequence-based testing on viruses isolated in cell culture is time consuming and less likely to detect the low-level presence of drug-resistant virus populations. we have developed a novel rolling circle amplification (rca) method to achieve the sensitive detection of otv-resistant virus ... | 2009 | 19800370 |
efficacy and safety of a live attenuated influenza vaccine in adults 60 years of age and older. | this randomized, double-blind, placebo-controlled study investigated the efficacy, safety, and immunogenicity of laiv in community-dwelling ambulatory adults > or =60 years of age in south africa in 2001. nose and throat swabs were obtained for influenza virus culture based on the symptoms of influenza-like illness. a total of 3242 subjects were enrolled, with a mean age of 69.5 years. the efficacy of laiv against influenza viruses antigenically similar to the vaccine was 42.3% (95% ci, 21.6-57. ... | 2009 | 19796721 |
switching gears for an influenza pandemic: validation of a duplex reverse transcriptase pcr assay for simultaneous detection and confirmatory identification of pandemic (h1n1) 2009 influenza virus. | rapid methods for the detection and confirmatory identification of pandemic influenza a virus (also known as pandemic [h1n1] 2009) are of utmost importance. in this study, a conventional reverse transcriptase pcr (rt-pcr) assay for the detection of influenza a virus and the hemagglutinin of swine lineage h1 (swh1) was designed, optimized, and validated. nucleic acids were extracted from 198 consecutive nasopharyngeal, nasal, or throat swab specimens collected early in the outbreak (127 negative ... | 2009 | 19794033 |
comparison of the usefulness of the caco-2 cell line with standard substrates for isolation of swine influenza a viruses. | influenza a virus isolation is undertaken routinely in embryonated chicken eggs, but to improve virus detection various cell lines can be used. the caco-2 cell line was compared to the mdck cell line and embryonated chicken eggs for the isolation of h1n1, h1n2, h3n2 swine influenza a virus subtypes from clinical specimens. from 2006 to 2008, 104 influenza a samples found positive by pcr from 42 respiratory outbreaks in italian swine farms were examined by virus isolation. sixty swine influenza a ... | 2010 | 19781571 |
comparative efficacy of inactivated and live attenuated influenza vaccines. | the efficacy of influenza vaccines may vary from year to year, depending on a variety of factors, and may differ for inactivated and live attenuated vaccines. | 2009 | 19776407 |
evaluation of twenty rapid antigen tests for the detection of human influenza a h5n1, h3n2, h1n1, and b viruses. | twenty rapid antigen assays were compared for their ability to detect influenza using dilutions of virus culture supernatants from human isolates of influenza a h5n1 (clade 1 and 2 strains), h3n2 and h1n1 viruses, and influenza b. there was variation amongst the rapid antigen assays in their ability to detect different influenza viruses. six of the 12 assays labeled as distinguishing between influenza a and b had comparable analytical sensitivities for detecting both influenza a h5n1 strains, al ... | 2009 | 19774693 |
the feasibility of using high resolution genome sequencing of influenza a viruses to detect mixed infections and quasispecies. | the rapidly expanding availability of de novo sequencing technologies can greatly facilitate efforts to monitor the relatively high mutation rates of influenza a viruses and the detection of quasispecies. both the mutation rates and the lineages of influenza a viruses are likely to play an important role in the natural history of these viruses and the emergence of phenotypically and antigenically distinct strains. | 2009 | 19771155 |
pandemic influenza as a current threat. | pandemics of influenza emerge from the aquatic bird reservoir, adapt to humans, modify their severity, and cause seasonal influenza. the catastrophic spanish h1n1 virus may have obtained all of its eight gene segments from the avian reservoir, whereas the asian h2n2 and the hong kong h3n2 pandemics emerged by reassortment between the circulating human virus and an avian h2 or h3 donor. of the 16 hemagglutinin subtypes, the h2, h5, h6, h7, and h9 viruses are considered to have pandemic potential. ... | 2009 | 19768398 |
an influenza a h1n1 virus revival - pandemic h1n1/09 virus. | in april 2009, a novel h1n1 influenza a virus, the so-called pandemic h1n1/09 virus (former designations include swine influenza, novel influenza, swine-origin influenza a [h1n1] virus [s-oiv], mexican flu, north american flu) was identified in mexico. the virus has since spread throughout the world and caused an influenza pandemic as defined by the criteria of the world health organization. this represents the first influenza a virus pandemic since the emergence of h3n2 (''hong kong'' flu) in 1 ... | 2009 | 19768379 |
[anti-viral effects of tankejing preparations against influenza virus a]. | to investigate the anti-viral effects of tankejing preparations (including solutions, dry power inhalation and powder) against influenza virus a in vitro and the relationship between its anti-viral effect and preparations. | 2009 | 19764333 |
rapid quantification of single-nucleotide mutations in mixed influenza a viral populations using allele-specific mixture analysis. | monitoring antiviral resistance in influenza is critical to public health epidemiology and pandemic preparedness activities. effective monitoring requires methods to detect low-level resistance and to monitor the change in resistance as a function of time and drug treatment. resistance-conferring single-nucleotide mutations in influenza virus are ideal targets for such methods. in the present study, fives sets of paired taqman allele-specific pcr (aspcr) assays were developed and validated for q ... | 2010 | 19761797 |
detection of influenza a(h1n1)v virus by real-time rt-pcr. | influenza a(h1n1)v virus was first identified in april 2009. a novel real-time rt-pcr for influenza a(h1n1)v virus was set up ad hoc and validated following industry-standard criteria. the lower limit of detection of the assay was 384 copies of viral rna per ml of viral transport medium (95% confidence interval: 273-876 rna copies/ml). specificity was 100% as assessed on a panel of reference samples including seasonal human influenza a virus h1n1 and h3n2, highly pathogenic avian influenza a vir ... | 2009 | 19758541 |
influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs. | this study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (mmf). side effects were investigated. | 2010 | 19758368 |
single residue deletions along the length of the influenza ha fusion peptide lead to inhibition of membrane fusion function. | a panel of eight single amino acid deletion mutants was generated within the first 24 residues of the fusion peptide domain of the of the hemagglutinin (ha) of a/aichi/2/68 influenza a virus (h3n2 subtype). the mutant has were analyzed for folding, cell surface transport, cleavage activation, capacity to undergo acid-induced conformational changes, and membrane fusion activity. we found that the mutant deltaf24, at the c-terminal end of the fusion peptide, was expressed in a non-native conformat ... | 2009 | 19755201 |
recent human influenza a/h3n2 virus evolution driven by novel selection factors in addition to antigenic drift. | examination of the evolutionary dynamics of complete influenza viral genomes reveals that other processes, in conjunction with antigenic drift, play important roles in viral evolution and selection, but there is little biological evidence to support these genomic data. previous work demonstrated that after the a/fujian/411/2002-like h3n2 influenza a epidemic during 2003-2004, a preexisting nondominant fujian-like viral clade gained a small number of changes in genes encoding the viral polymerase ... | 2009 | 19743921 |
detection and subtyping of influenza a virus based on a short oligonucleotide microarray. | we report the design and characterization of a microarray with 46 short virus-specific oligonucleotides for detecting influenza a virus of 5 subtypes: h1n1, h1n2, h3n2, h5n1, and h9n2. a unique combination of 3 specific modifications was introduced into the microarray assay: (1) short probes of 19 to 27 nucleotides, (2) simple amplification of full-length hemagglutinin and neuraminidase cdnas with universal primers, and (3) klenow-mediated labeling and further amplification of the samples before ... | 2009 | 19733996 |
virologically confirmed population-based burden of hospitalization caused by influenza a and b among children in hong kong. | we sought to determine the virologically confirmed hospitalization rates associated with influenza virus infection among hong kong children. | 2009 | 19722912 |
identification of amino acid residues of influenza a virus h3 ha contributing to the recognition of molecular species of sialic acid. | to identify a determinant of human h3 hemagglutinin (ha) amino acid residues linked to the recognition of molecular species of sialic acid, we generated six mutant viruses possessing either the wild-type ha gene from a/memphis/1/71 (h3n2) or a genetically single-mutated ha gene at position 137, 144, 155, 158 or 193 from a genetic backbone of a/wsn/33 (h1n1) by reverse genetics. we evaluated the binding ability with four types of synthetic sialylglycolipids. the results indicate that the amino ac ... | 2009 | 19720062 |
differences in patient age distribution between influenza a subtypes. | since the spring of 1977, two subtypes of influenza a virus (h3n2 and h1n1) have been seasonally infecting the human population. in this work we study the distribution of patient ages within the populations that exhibit the symptomatic disease caused by each of the different subtypes of seasonal influenza viruses. when the publicly available extensive information is pooled across multiple geographical locations and seasons, striking differences emerge between these subtypes. we report that the s ... | 2009 | 19718262 |
[comparative study of avian influenza virus propagation in the cell culture and chick embryos]. | comparative reproduction studies of 7 avian influenza virus strains (h5n1, h5n2, h3n2, h4n6, h7n7) in vero and mdck cell lines have indicated that the mdck cell line is an optimal substrate for all study strains. the maximum viral output depends on trypsin concentrations and infection doses, which can differ for individual viral strains. the use of the optimal parameters of avian influenza virus replication in the mdck cell lines yields virus titers comparable with virus reproduction in the chic ... | 2009 | 19708550 |
using a mutual information-based site transition network to map the genetic evolution of influenza a/h3n2 virus. | mapping the antigenic and genetic evolution pathways of influenza a is of critical importance in the vaccine development and drug design of influenza virus. in this article, we have analyzed more than 4000 a/h3n2 hemagglutinin (ha) sequences from 1968 to 2008 to model the evolutionary path of the influenza virus, which allows us to predict its future potential drifts with specific mutations. | 2009 | 19706746 |
differential suppressive effect of promyelocytic leukemia protein on the replication of different subtypes/strains of influenza a virus. | promyelocytic leukemia protein (pml) plays an important role in the defense against a number of viruses, including influenza a virus. however, the sensitivity of influenza a virus subtypes/strains to pml is unknown. we investigated the role of pml in the replication of different influenza a virus subtypes/strains using pan-pml knock-down a549 cells and pml-vi-overexpressed mdck cells. we found that (i) depletion of pan-pml by sirna rendered a549 cells more susceptible to influenza a virus strain ... | 2009 | 19703418 |
influenza epidemiology and characterization of influenza viruses in patients seeking treatment for acute fever in cambodia. | the epidemiology, symptomology, and viral aetiology of endemic influenza remain largely uncharacterized in cambodia. in december 2006, we established passive hospital-based surveillance to identify the causes of acute undifferentiated fever in patients seeking healthcare. fever was defined as tympanic membrane temperature >38 degrees c. from december 2006 to december 2008, 4233 patients were screened for influenza virus by real-time reverse-transcriptase polymerase chain reaction (rrt-pcr). of t ... | 2010 | 19698213 |
h3n2 influenza a virus replicates in immortalized human first trimester trophoblast cell lines and induces their rapid apoptosis. | epidemiological data suggested that pandemic influenza increased the risks of spontaneous abortion and premature labor, while seasonal influenza also increased the risk of schizophrenia in adolescence. however, their pathogenesis is so far unknown. | 2009 | 19694639 |
what will the next influenza season bring about: seasonal influenza or the new a(h1n1)v? an analysis of german influenza surveillance data. | for the next influenza season (winter 2009-10) the relative contributions to virus circulation and influenza-associated morbidity of the seasonal influenza viruses a(h3n2), a(h1n1) and b, and the new influenza a(h1n1)v are still unknown. we estimated the chances of seasonal influenza to circulate during the upcoming season using data of the german influenza sentinel scheme from 1992 to 2009. we calculated type and subtype-specific indices for past exposure and the corresponding morbidity indices ... | 2009 | 19679036 |
mechanisms of the action of povidone-iodine against human and avian influenza a viruses: its effects on hemagglutination and sialidase activities. | influenza virus infection causes significant morbidity and mortality and has marked social and economic impacts throughout the world. the influenza surface glycoproteins, hemagglutinin (ha) and neuraminidase (na), act cooperatively to support efficient influenza a virus replication and provide the most important targets for anti-influenza chemotherapy. in this study, povidone-iodine (pvp-i), which has a broad-spectrum microbicidal property, was examined for its inhibitory effects against influen ... | 2009 | 19678928 |
[rescue of h3n2 subtype swine influenza virus and substitution of hemagglutinin, neuraminidase]. | to study the mechanisms of trans-species transmission of influenza virus for developing novel vaccine of influenza in future. | 2009 | 19673419 |
antibodies to pb1-f2 protein are induced in response to influenza a virus infection. | pb1-f2 is a small influenza a virus (iav) protein encoded by an alternative (+1) reading frame of the pb1 gene. while dispensable for iav replication in cultured cells, pb1-f2 has been implicated in iav pathogenicity. to better understand pb1-f2 expression in vivo and its immunogenicity, we analyzed anti-pb1-f2 antibodies (abs) in sera of mice infected intranasally (i.n.) with a/pr/8/34 (h1n1) virus and human acute and convalescent sera collected from the influenza h3n2 winter 2003-2004 epidemic ... | 2009 | 19672555 |
[cloning and characterization of m1 gene of h3n2 subtype swine influenza virus]. | influenza a virus matrix protein (m1) is encoded by a spliced mrna derived from rna segment 7 and plays an important role in the virus life cycle. in the present study, we extracted the viral genome rnas from allantoic fluid of 9-day-old embryonated chicken eggs infected with swine influenza a virus (siv) h3n2 subtype and amplified the siv m1 gene by reverse transcriptase-polymerase chain reaction using the isloated viral genome rnas as template. the amplified cdna was cloned into an expression ... | 2009 | 19670634 |
evaluation of rapid influenza diagnostic tests for detection of novel influenza a (h1n1) virus - united states, 2009. | the recent appearance and worldwide spread of novel influenza a (h1n1) virus has highlighted the need to evaluate commercially available, widely used, rapid influenza diagnostic tests (ridts) for their ability to detect these viral antigens in respiratory clinical specimens. as an initial assessment, cdc conducted an evaluation of multiple ridts. sixty-five clinical respiratory specimens collected during april-may 2009 that had previously tested positive either for novel influenza a (h1n1) or fo ... | 2009 | 19661856 |
a dose-ranging study of a subunit respiratory syncytial virus subtype a vaccine with and without aluminum phosphate adjuvantation in adults > or =65 years of age. | we studied the safety and immunogenicity of a respiratory syncytial virus (rsv)-a vaccine containing subunit antigens f, g and m in older persons, and its effect on influenza vaccine immunogenicity. in a dose-ranging, placebo-controlled, blinded trial 561 adults > or =65 years of age at five canadian sites were randomized to one intramuscular injection of either 100, 50 or 25 microg rsv-a-alum vaccine or 100 microg non-adjuvanted rsv-a vaccine, or alum-placebo. all participants were offered inac ... | 2009 | 19651171 |
prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices (acip), 2009. | this report updates the 2008 recommendations by cdc's advisory committee on immunization practices (acip) regarding the use of influenza vaccine for the prevention and control of seasonal influenza (cdc. prevention and control of influenza: recommendations of the advisory committee on immunization practices [acip]. mmwr 2008;57[no. rr-7]). information on vaccination issues related to the recently identified novel influenza a h1n1 virus will be published later in 2009. the 2009 seasonal influenza ... | 2009 | 19644442 |
rapid multiplex reverse transcription-pcr typing of influenza a and b virus, and subtyping of influenza a virus into h1, 2, 3, 5, 7, 9, n1 (human), n1 (animal), n2, and n7, including typing of novel swine origin influenza a (h1n1) virus, during the 2009 outbreak in milwaukee, wisconsin. | a large outbreak of novel influenza a (h1n1) virus (swine origin influenza virus [s-oiv]) infection in milwaukee, wi, occurred in late april 2009. we had recently developed a rapid multiplex reverse transcription-pcr enzyme hybridization assay (fluplex) to determine the type (a or b) and subtype (h1, h2, h3, h5, h7, h9, n1 [human], n1 [animal], n2, or n7) of influenza viruses, and this assay was used to confirm the diagnoses for the first infected patients in the state. the analytical sensitivit ... | 2009 | 19641063 |
[elicitation of protective immune responses by a recombinant adenovirus expressing hemagglutinin of h3n2 siv in swine]. | to evaluate the immunity of the adenovirus recombinant rad-ha-gfp encoding an h3n2 swine influenza virus hemagglutinin. | 2009 | 19637575 |
two genotypes of h1n2 swine influenza viruses appeared among pigs in china. | h1n2 is one of the main subtypes of influenza, which circulates in swine all over the world. | 2009 | 19632889 |
synthesis of sialic acid derivatives having a c=c double bond substituted at the c-5 position and their glycopolymers. | glycomonomers of sialic acid in which the acetamide group at c-5 was converted into two kinds of c=c double bond substituents were prepared and the fully protected glycomonomers were directly polymerized before deprotection steps. radical polymerization with acrylamide in dmf in the presence of ammonium persulfate and n,n,n',n'-tetramethylethylenediamine proceeded smoothly and gave corresponding sialopolymers. interestingly glycomonomers had hemagglutination inhibitory activities not only for h1 ... | 2009 | 19631531 |
elastase-dependent live attenuated swine influenza a viruses are immunogenic and confer protection against swine influenza a virus infection in pigs. | influenza a viruses cause significant morbidity in swine, resulting in a substantial economic burden. swine influenza virus (siv) infection also poses important human public health concerns. vaccination is the primary method for the prevention of influenza virus infection. previously, we generated two elastase-dependent mutant sivs derived from a/sw/saskatchewan/18789/02(h1n1): a/sw/sk-r345v (r345v) and a/sw/sk-r345a (r345a). these two viruses are highly attenuated in pigs, making them good cand ... | 2009 | 19625412 |
[monitoring of antibodies to influenza a virus in populations of different regions of west siberia]. | to study levels of antibodies to influenza virus in sera of subjects residing in different regions of west siberia in order to assess the risk of infection with avian influenza virus h5n1. | 2009 | 19621827 |
[influenza surveillance results in 2007-2008 winter season in nine provinces of turkey]. | influenza virus infections constitute a serious public health problem owing to their epidemic and pandemic potential. turkish ministry of health established the national influenza surveillance programme in two institutes to detect the virus types leading to the illness and the efficiency of the seasonal vaccine. influenza surveillance is performed by refik saydam hygiene center, national influenza laboratory in nine provinces (which are located at central, northeast, south and east parts of turk ... | 2009 | 19621608 |
triple combination of oseltamivir, amantadine, and ribavirin displays synergistic activity against multiple influenza virus strains in vitro. | the recurring emergence of influenza virus strains that are resistant to available antiviral medications has become a global health concern, especially in light of the potential for a new influenza virus pandemic. currently, virtually all circulating strains of influenza a virus in the united states are resistant to either of the two major classes of anti-influenza drugs (adamantanes and neuraminidase inhibitors). thus, new therapeutic approaches that can be rapidly deployed and that will addres ... | 2009 | 19620324 |
procedures to eliminate h3n2 swine influenza virus from a pig herd. | a three-site pig herd infected with a h3n2 swine influenza virus (siv) underwent a herd siv elimination programme using herd closure and partial depopulation. the herd consisted of sow, nursery and finishing units, 1 to 2 km apart. disease was noted in the sow unit and then the nursery unit. the herd temporarily stopped introduction of replacement animals, and replacement gilt introductions in the breeding herd was changed from monthly to quarterly. gilts from a serologically negative source wer ... | 2009 | 19617611 |
pathogen exposure in feral swine populations geographically associated with high densities of transitional swine premises and commercial swine production. | surveys for evidence of exposure to pseudorabies virus (prv), brucella suis, swine influenza virus (siv; human-like h1n1, reassortant type h1n1, h1n2-like h1n1 and h3n2), porcine circovirus 2 (pcv 2), and porcine respiratory and reproductive syndrome virus (prrsv) in feral swine (sus scrofa) were conducted in areas where feral swine were geographically associated with high densities of transitional swine premises in south carolina and high densities of commercial swine production in north caroli ... | 2009 | 19617481 |
evaluation of the efficacy and safety of a statin/caffeine combination against h5n1, h3n2 and h1n1 virus infection in balb/c mice. | the development of novel antiviral drugs is necessary for the prevention and treatment of a potential avian influenza pandemic. the aim of this study was to evaluate the efficacy and safety of a novel statin/caffeine combination against h5n1, h3n2 and h1n1 virus infection in a murine model. in h5n1-, h3n2- and h1n1-infected balb/c mice, 50mug statin/200mug caffeine effectively ameliorated lung damage and inhibited viral replication and was at least as effective as oseltamivir and ribavirin. the ... | 2009 | 19616097 |
molecular and phylogenetic analysis and vaccine strain match of human influenza a(h3n2) viruses isolated in northern greece between 2004 and 2008. | influenza a viruses are characterized by a unique genome structure, causing genetic instability, especially to the genes of haemagglutinin and neuraminidase. the objectives of this research was molecular and phylogenetic analysis of influenza a(h3n2) strains that circulated in northern greece since 2004, particularly the identification of sequence variations and the comparison of circulating viruses with vaccine strains. since 2004 in northern greece, a total of 216 clinical samples were positiv ... | 2009 | 19615420 |
single-reaction genomic amplification accelerates sequencing and vaccine production for classical and swine origin human influenza a viruses. | pandemic influenza a viruses that emerge from animal reservoirs are inevitable. therefore, rapid genomic analysis and creation of vaccines are vital. we developed a multisegment reverse transcription-pcr (m-rtpcr) approach that simultaneously amplifies eight genomic rna segments, irrespective of virus subtype. m-rtpcr amplicons can be used for high-throughput sequencing and/or cloned into modified reverse-genetics plasmids via regions of sequence identity. we used these procedures to rescue a co ... | 2009 | 19605485 |
dating the emergence of pandemic influenza viruses. | pandemic influenza viruses cause significant mortality in humans. in the 20th century, 3 influenza viruses caused major pandemics: the 1918 h1n1 virus, the 1957 h2n2 virus, and the 1968 h3n2 virus. these pandemics were initiated by the introduction and successful adaptation of a novel hemagglutinin subtype to humans from an animal source, resulting in antigenic shift. despite global concern regarding a new pandemic influenza, the emergence pathway of pandemic strains remains unknown. here we est ... | 2009 | 19597152 |
dynamics of antiviral-resistant influenza viruses in the netherlands, 2005-2008. | in the netherlands, influenza specific antivirals are used for the therapy of influenza in nursing homes and hospitals, for prophylaxis in high risk groups and neuraminidase inhibitors are stockpiled as part of pandemic preparedness plans. to monitor the antiviral susceptibility profile, human influenza virus isolates derived from the dutch influenza surveillance in 2005-2006 (n=87), 2006-2007 (n=58) and 2007-2008 (n=128) were analyzed with phenotypic assays and sequencing. for adamantanes, a hi ... | 2009 | 19591877 |
viral loads and duration of viral shedding in adult patients hospitalized with influenza. | the goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza. | 2009 | 19591575 |
syntheses and biological evaluations of carbosilane dendrimers uniformly functionalized with sialyl alpha(2-->3) lactose moieties as inhibitors for human influenza viruses. | a series of carbosilane dendrimers uniformly functionalized with sialyl lactose moieties (neu5ac alpha2-->3gal beta1-->4glc) was systematically synthesized, and biological evaluations for anti-influenza virus activity using the glycodendrimers were performed. the results suggested that the glycodendrimers had unique biological activities depending on the form of their core frame, and dumbbell(1)6-amide type glycodendrimer 7 showed particularly strong inhibitory activities against human influenza ... | 2009 | 19589684 |
pomegranate (punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir. | influenza epidemics cause numerous deaths and millions of hospitalizations each year. because of the alarming emergence of resistance to anti-influenza drugs, there is a need to identify new naturally occurring antiviral molecules. we tested the hypothesis that pomegranate polyphenol extract (ppe) has anti-influenza properties. using real time pcr, plaque assay, and tcid 50% hemagglutination assay, we have shown that ppe suppresses replication of influenza a virus in mdck cells. ppe inhibits agg ... | 2009 | 19586764 |
broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors. | human monoclonal antibodies (humabs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named spymeg, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influe ... | 2009 | 19580789 |
influenza-like illness sentinel surveillance in peru. | acute respiratory illnesses and influenza-like illnesses (ili) are a significant source of morbidity and mortality worldwide. despite the public health importance, little is known about the etiology of these acute respiratory illnesses in many regions of south america. in 2006, the peruvian ministry of health (moh) and the us naval medical research center detachment (nmrcd) initiated a collaboration to characterize the viral agents associated with ili and to describe the clinical and epidemiolog ... | 2009 | 19568433 |
differential transcription-activating capability of ns1 proteins from different influenza virus subtypes expressed in yeast. | influenza a virus ns1 protein is an important regulatory factor with multiple functions and contributes greatly to viral pathogenesis. in the present study, transcription-activating potential of ns1 from different influenza a virus subtypes was examined in yeast two-hybrid system. the bait vectors containing different ns1 genes, along with an empty prey vector, were transformed into yeast ah109(for growth assay on qdo plate and alpha-galactosidase assay), and y187(for beta-galactosidase assay). ... | 2009 | 19557332 |
a trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets. | there is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. we have engineered an influenza virus-like particle (vlp) as a new generation vaccine candidate purified from the supernatants of sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (ha), neuram ... | 2009 | 19554101 |
infection of human retinal pigment epithelial cells with influenza a viruses. | ocular involvement in influenza a virus diseases is common but usually limited to mild conjunctivitis. rarely, inflammation of the choriocapillaris may result in atrophia of the retinal pigment epithelium (rpe). primary human retinal pigment epithelial (rpe) cells were infected with seasonal (h1n1 a/new caledonia/20/99, h3n2 a/california/7/2004) or highly pathogenic avian h5n1 (a/thailand/1(kan-1)/04, a/vietnam/1203/04, a/vietnam/1194/04) influenza strains. | 2009 | 19553611 |
mixed infection and the genesis of influenza virus diversity. | the emergence of viral infections with potentially devastating consequences for human health is highly dependent on their underlying evolutionary dynamics. one likely scenario for an avian influenza virus, such as a/h5n1, to evolve to one capable of human-to-human transmission is through the acquisition of genetic material from the a/h1n1 or a/h3n2 subtypes already circulating in human populations. this would require that viruses of both subtypes coinfect the same cells, generating a mixed infec ... | 2009 | 19553313 |
palmitoylation of the influenza a virus m2 protein is not required for virus replication in vitro but contributes to virus virulence. | the influenza a virus m2 protein has important roles during virus entry and in the assembly of infectious virus particles. the cytoplasmic tail of the protein can be palmitoylated at a cysteine residue, but this residue is not conserved in a number of human influenza a virus isolates. recombinant viruses encoding m2 proteins with a serine substituted for the cysteine at position 50 were generated in the a/wsn/33 (h1n1) and a/udorn/72 (h3n2) genetic backgrounds. the recombinant viruses were not a ... | 2009 | 19553312 |
t-cell tolerance for variability in an hla class i-presented influenza a virus epitope. | to escape immune recognition, viruses acquire amino acid substitutions in class i human leukocyte antigen (hla)-presented cytotoxic t-lymphocyte (ctl) epitopes. such viral escape mutations may (i) prevent peptide processing, (ii) diminish class i hla binding, or (iii) alter t-cell recognition. because residues 418 to 426 of the hypervariable influenza a virus nucleoprotein (np(418-426)) epitope are consistently bound by class i hla and presented to ctl, we assessed the impact that intraepitope s ... | 2009 | 19553306 |
lower cellular immune responses to influenza a (h3n2) in the elderly. | influenza epidemic is an important cause of severe illness in the elderly. age-dependent morbidity of influenza in the elderly is associated with weakened immunity. the baseline age-related memory t cell activity in chinese persons who are exposed to influenza virus through natural infection, are associated with the protective response to the virus after vaccination, thus providing important pre-vaccination information. a cohort from the general population was established at the end of an influe ... | 2009 | 19551830 |
influenza a virus in taiwan, 1980-2006: phylogenetic and antigenic characteristics of the hemagglutinin gene. | limited amount of information is available in taiwan on the genetic or antigenic characteristics of influenza a virus prior to the establishment of a taiwan surveillance network in 2000. isolates of h1n1 and h3n2 viruses in taiwan between 1980 and 2006 were studied, and part of the hemagglutinin gene was analyzed due to its importance in terms of viral infection and antibody neutralization. results from a phylogenetic analysis indicate continuous evolutionary topology in h3n2 isolates, and two d ... | 2009 | 19551820 |
structural and evolutionary characteristics of ha, na, ns and m genes of clinical influenza a/h3n2 viruses passaged in human and canine cells. | canine (mdck) cells and chicken eggs are usually used for isolation of human influenza viruses. viruses isolated by these procedures often differ from those present in the clinical specimens, since adaptive changes occur during virus transmission from the human host to cells of heterologous origin. | 2009 | 19546028 |
emergence of a novel swine-origin influenza a virus (s-oiv) h1n1 virus in humans. | a recently emerged novel influenza a h1n1 virus continues to spread globally. the virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in swine and it likely arose through reassortment of two or more viruses of swine origin. h1n1, h1n2 and h3n2 subtype swine influenza viruses have occasionally infected humans before but such zoonotic transmission events did not lead to sustained human-to-human transmission in the manner this swine-origin influen ... | 2009 | 19540800 |
development of a real-time rt-pcr for the detection of swine-lineage influenza a (h1n1) virus infections. | a novel influenza a virus, subtype h1n1 of swine-lineage (h1n1 swl) has transmitted rapidly to many regions of the world with evidence of sustained transmission within some countries. rapid detection and differentiation from seasonal influenza is essential to instigate appropriate patient and public health management and for disease surveillance. | 2009 | 19540799 |
evaluation of multiple test methods for the detection of the novel 2009 influenza a (h1n1) during the new york city outbreak. | in response to the novel influenza a h1n1 outbreak in the ny city area, 6090 patient samples were submitted over a 5-week period for a total of 14,114 viral diagnostic tests, including rapid antigen, direct immunofluorescence (dfa), viral culture and pcr. little was known about the performance of the assays for the detection of novel h1n1 in the background of seasonal h1n1, h3n2 and other circulating respiratory viruses. in addition, subtyping influenza a became critical for the identification o ... | 2009 | 19540158 |
fecal detection of influenza a virus in patients with concurrent respiratory and gastrointestinal symptoms. | in seasonal influenza, gastrointestinal symptoms such as diarrhea, vomiting, and abdominal pain are sometimes observed, especially among young children. however, fecal excretion of seasonal influenza virus has seldom been studied. | 2009 | 19540157 |
preparing the outbreak assistance laboratory network in the netherlands for the detection of the influenza virus a(h1n1) variant. | late april 2009, human infection with variant influenza virus a(h1n1)v emerged in the northern americas posing a threat that this virus may become the next pandemic influenza virus. | 2009 | 19540155 |
infection of mice with a human influenza a/h3n2 virus induces protective immunity against lethal infection with influenza a/h5n1 virus. | the transmission of highly pathogenic avian influenza (hpai) a viruses of the h5n1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. however, prior infections with seasonal influenza a/h1n1 and a/h3n2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the hpai a/h5n1 viruses, which are distantly related to the human influenza a viruses. to assess the protective ef ... | 2009 | 19538996 |
pathogenesis and subsequent cross-protection of influenza virus infection in pigs sustained by an h1n2 strain. | the h1n1, h3n2 and, more recently, h1n2 subtypes of influenza a virus are presently co-circulating in swine herds in several countries. the objectives of this study were to investigate the pathogenesis of sw/italy/1521/98 (h1n2) influenza virus, isolated from respiratory tissues of pigs from herds in northern italy, and to evaluate its potential cross-protection against the sw/fin/2899/82 (h1n1) strain. in the pathogenesis test, eight pigs were intranasally infected with h1n2 virus; at pre-deter ... | 2010 | 19538454 |
amantadine-resistant influenza a (h3n2) viruses in iran. | adamantanes have been used for the prophylaxis and treatment of influenza a virus (iav) infections worldwide. however, they have limited use because of increasing number of resistant viruses during recent years. in investigating the frequency of amantadine-resistant iavs (h3n2) circulating in iran in 2005-2008, we found that m2 sequences of recently circulating viruses that were amantadine-resistant contained a ser31asn mutation. thus, adamantanes should not be used for treatment or prophylaxis ... | 2009 | 19537916 |
[type and subtype distribution of influenza virus and genetic evolution of hemagglutinin in shanghai area in duration of 2004 - 2008]. | to analyze the type and subtype distribution of influenza virus and the genetic evolution of hemagglutinin (ha) in shanghai area during 2004 to 2008. | 2009 | 19534952 |
risk factors associated with pleuritis and cranio-ventral pulmonary consolidation in slaughter-aged pigs. | examination of lung lesions at the slaughterhouse is a useful tool to estimate the importance of respiratory disease at farm, regional or national level. the objective of the present work was to describe the prevalence of gross lung lesions at slaughter, with a special focus on pleuritis and cranio-ventral pulmonary consolidation, and to identify major risk factors for these lesions. data from 107 farms involving approximately 11,000 pigs enabled gross lung lesions to be correlated with serology ... | 2010 | 19527939 |
detection of novel influenza a(h1n1) virus by real-time rt-pcr. | accurate and rapid diagnosis of novel influenza a(h1n1) infection is critical for minimising further spread through timely implementation of antiviral treatment and other public health based measures. in this study we developed two taqman-based reverse transcription pcr (rt-pcr) methods for the detection of novel influenza a(h1n1) virus targeting the haemagglutinin and neuraminidase genes. the assays were validated using 152 clinical respiratory samples, including 61 influenza a positive samples ... | 2009 | 19515611 |
study of efficiency of therapeutic and preventive anaferon (pediatric formulation) in mice with influenza infection. | therapeutic and preventive treatment of mice intranasally infected with a lethal dose of a/aichi/2/68 (h3n2) influenza virus with anaferon (pediatric formulation) demonstrated an antiviral effect of the drug (increased percent of survivors and prolonged lifespan). | 2008 | 19513378 |
co-circulation of two genetically distinct sub-groups of a/h3n2 influenza strains during the 2006-2007 epidemic season in corsica island, france. | influenza virus is one of the major viral respiratory pathogens infecting human beings. | 2009 | 19502107 |
mechanism of the antiviral effect of hydroxytyrosol on influenza virus appears to involve morphological change of the virus. | hydroxytyrosol (ht), a small-molecule phenolic compound, inactivated influenza a viruses including h1n1, h3n2, h5n1, and h9n2 subtypes. ht also inactivated newcastle disease virus but not bovine rotavirus, and fowl adenovirus, suggesting that the mechanism of the antiviral effect of ht might require the presence of a viral envelope. pretreatment of mdck cells with ht did not affect the propagation of h9n2 virus subsequently inoculated onto the cells, implying that ht targets the virus but not th ... | 2009 | 19501255 |
genetic and antigenic evolution of swine influenza viruses in europe and evaluation of their zoonotic potential. | swine influenza is a highly contagious respiratory viral infection of pigs that has become enzootic in areas densely populated with pigs. like other influenza a viruses, swine influenza virus (siv) is genetically unstable and able to accumulate antigenic drifts and/or antigenic shifts. the pig is susceptible to both avian and human influenza viruses and can serve as an intermediate host in influenza virus ecology. zoonotic agents may emerge in pigs following the modification of an established sw ... | 2009 | 19497089 |
antiviral resistance in influenza viruses circulating in central and south america based on the detection of established genetic markers. | recent influenza antiviral resistance studies reveal an alarming increase in both adamantanes and neuraminidase inhibitors (nais) resistant viral strains worldwide, particularly in asia, europe and the united states. | 2009 | 19496844 |
reassortment between avian h5n1 and human h3n2 influenza viruses in ferrets: a public health risk assessment. | this study investigated whether transmissible h5 subtype human-avian reassortant viruses could be generated in vivo. to this end, ferrets were coinfected with recent avian h5n1 (a/thailand/16/04) and human h3n2 (a/wyoming/3/03) viruses. genotype analyses of plaque-purified viruses from nasal secretions of coinfected ferrets revealed that approximately 9% of recovered viruses contained genes from both progenitor viruses. h5 and h3 subtype viruses, including reassortants, were found in airways ext ... | 2009 | 19493997 |
protein intrinsic disorder and influenza virulence: the 1918 h1n1 and h5n1 viruses. | the 1918 h1n1 virus was a highly virulent strain that killed 20-50 million people. the cause of its virulence remains poorly understood. | 2009 | 19493338 |
cluster analysis of the origins of the new influenza a(h1n1) virus. | in march and april 2009, a new strain of influenza a(h1n1) virus has been isolated in mexico and the united states. since the initial reports more than 10,000 cases have been reported to the world health organization, all around the world. several hundred isolates have already been sequenced and deposited in public databases. we have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. we show that the new virus combines genetic informa ... | 2009 | 19480812 |
attenuated antibody reaction for the primary antigen but not for the recall antigen of influenza vaccination in patients with non-hodgkin b-cell lymphoma after the administration of rituximab-chop. | to assess the humoral response to the influenza vaccine in patients undergoing r-chop therapy (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and predonisolone) for non-hodgkin lymphoma (nhl), the anti-hemagglutinin (ha) titer in 7 nhl patients undergoing therapy was compared with those in 10 control group subjects in the 2005/2006 season. four weeks after vaccination, the ha titers against the influenza type a h1n1 and type b antigens, the same antigens that had been used i ... | 2009 | 19474512 |
high genetic and antigenic similarity between a swine h3n2 influenza a virus and a prior human influenza vaccine virus: a possible immune pressure-driven cross-species transmission. | in late april of 2009, a global outbreak of human influenza was reported. the causative agent is a highly unusual reassortant h1n1 influenza virus carrying genetic segments derived from swine, human and avian influenza viruses. in this study, we compared the ha, na and other gene segments of a swine h3n2 influenza a virus, a/swine/guangdong/z5/2003, which was isolated from pigs in 2003 in guangdong province, china, to the predominant human and swine h3n2 viruses. we found that the similarity of ... | 2009 | 19463787 |
full factorial analysis of mammalian and avian influenza polymerase subunits suggests a role of an efficient polymerase for virus adaptation. | amongst all the internal gene segments (pb2. pb1, pa, np, m and ns), the avian pb1 segment is the only one which was reassorted into the human h2n2 and h3n2 pandemic strains. this suggests that the reassortment of polymerase subunit genes between mammalian and avian influenza viruses might play roles for interspecies transmission. to test this hypothesis, we tested the compatibility between pb2, pb1, pa and np derived from a h5n1 virus and a mammalian h1n1 virus. all 16 possible combinations of ... | 2009 | 19462010 |