Publications

sialidase activity of influenza a virus in an endocytic pathway enhances viral replication.	n2 neuraminidase (na) genes of the 1957 and 1968 pandemic influenza virus strains possessed avian-like low-ph stability of sialidase activity, unlike most epidemic strains. we generated four reverse-genetics viruses from a genetic background of a/wsn/33 (h1n1) that included parental n2 nas of 1968 pandemic (h3n2) and epidemic (h2n2) strains or their counterpart n2 nas in which the low-ph stability of the sialidase activity was changed by substitutions of one or two amino acid residues. we found ...	2005	16140748
influenza immunisation in children with solid tumours.	we assessed response to immunisation with trivalent split virus influenza vaccine in children with non-leukaemic malignant disease. children with solid tumours and lymphoma received one or two doses of influenza vaccine, according to current uk guidelines, in autumn 2001 and/or 2002. children were currently receiving chemotherapy or were within 6 months of completing chemotherapy. pre and post vaccination sera were assessed for antibodies to the prevalent influenza strains by haemagglutination i ...	2005	16143516
the origins of new pandemic viruses: the acquisition of new host ranges by canine parvovirus and influenza a viruses.	transfer of viruses between hosts to create a new self-sustaining epidemic is rare; however, those new viruses can cause severe outbreaks. examples of such viruses include three pandemic human influenza a viruses and canine parvovirus in dogs. in each case one virus made the original transfer and spread worldwide, and then further adaptation resulted in the emergence of variants worldwide. for the influenza viruses several changes were required for growth and spread between humans, and the emerg ...	2005	16153179
implementation of the community network of reference laboratories for human influenza in europe.	the increased need for accurate influenza laboratory surveillance data in the european union required formalisation of the existing network of collaborating national influenza reference laboratories participating in the european influenza surveillance scheme (eiss).	2005	16157259
the cotton rat provides a useful small-animal model for the study of influenza virus pathogenesis.	influenza a virus continues to cause annual epidemics. the emergence of avian viruses in the human population poses a pandemic threat, and has highlighted the need for more effective influenza vaccines and antivirals. development of such therapeutics would be enhanced by the use of a small-animal model that is permissive for replication of human influenza virus, and for which reagents are available to dissect the host response. a model is presented of nasal and pulmonary infection in adult inbre ...	2005	16186238
neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility.	mutations of the conserved residues of influenza virus neuraminidase (na) that are associated with na inhibitor (nai) resistance decrease the sialidase activity and/or stability of the na, thus compromising viral fitness. in fact, clinically derived nai-resistant variants with different na mutations have shown different transmissibilities in ferrets (m. l. herlocher, r. truscon, s. elias, h. yen, n. a. roberts, s. e. ohmit, and a. s. monto, j. infect. dis. 190:1627-1630, 2004). molecular charact ...	2005	16189083
[sequence analysis of the ha1 regions of hemagglutinin gene from influenza viruses (h3n2) isolated from children in beijing in 2004 indicated antigenic variation].	to identify variations in hemagglutinin genes from influenza viruses (h3n2) isolated from infants and young children with acute respiratory infection (ari) between march, 2004 and april 2005.	2005	16191295
characterization of different strains of poliovirus and influenza virus by differential scanning calorimetry.	vaccines against poliomyelitis and influenza contain inactivated forms of poliovirus and influenza virus. these antigens are generated on an industrial scale from the purified active viruses that have been analysed in this study by dsc (differential scanning calorimetry). multiple unfolding transitions are seen for influenza virus a/new caledonia/20/99 (h1n1), a/panama/2007/99 (h3n2) and b/shangdong/7/97. these data, combined with previously reported data on other influenza viruses, indicates th ...	2005	15377284
protection against influenza virus infection by intranasal administration of hemagglutinin vaccine with chitin microparticles as an adjuvant.	chitin in the form of microparticles (chitin microparticles, cmp) has been demonstrated to be a potent stimulator of macrophages, promoting t-helper-1 (th1) activation and cytokine response. in order to examine the mucosal adjuvant effect of cmp co-administered with influenza hemagglutinin (ha) vaccine against influenza infection, cmp were intranasally co-administered with influenza ha vaccine prepared from pr8 (h1n1) virus. inoculation of the vaccine with cmp induced primary and secondary anti- ...	2005	15543590
monoclonal antibodies versus reverse transcription-pcr for detection of respiratory viruses in a patient population with respiratory tract infections admitted to hospital.	in the winter season 2001-2002, 239 nasopharyngeal aspirate and 15 bronchoalveolar lavage samples from 208 patients (135 pediatric and 73 adults, including 19 lung transplant recipients) admitted to hospital because of an acute respiratory tract infection were examined for rapid diagnosis of respiratory viruses by two diagnostic approaches: immunological, using specific monoclonal antibodies (mab); and molecular, using specific reverse transcription (rt)-pcr assays. both methods detected influen ...	2005	15602736
a non-living nasal influenza vaccine can induce major humoral and cellular immune responses in humans without the need for adjuvants.	twenty-eight healthy adult volunteers were immunized intranasally with an inactivated whole-virus influenza vaccine based on the strain a/new caledonia/20/99 (h1n1), either in saline or mixed with formaldehyde-inactivated bordetella pertussis as a mucosal adjuvant, or in a thixotropic vehicle with mucoadhesive properties. after four doses, all groups of vaccinees developed significant igg- and iga-antibody responses, measured by elisa, in respectively serum and nasal secretions. none of the volu ...	2005	17038826
phase i, randomized, controlled trial to study the reactogenicity and immunogenicity of a nasal, inactivated trivalent influenza virus vaccine in healthy adults.	we performed a randomized, placebo-controlled, dose-escalating clinical trial to evaluate the safety and immunogenicity of an inactivated, split virion, trivalent, nasal influenza vaccine using lipid/polysaccharide molecules as carriers. a total of 64 adults (mean age 29; range 19-69 years) were randomly allocated to receive a mixture of lipid/polysaccharide carrier molecules and 7.5, 15, or 30 microg hemagglutinin antigen of each of the three influenza strains (a/johannesburg/82/96 [h1n1], a/na ...	2005	17038827
[in vitro study of antiviral activity of myramistin against subtypes h3n2 and h5n1 of influenza virus].	in vitro antiviral effect of myramistin on influenza virus (mdck cell culture) was studied. the drug showed significant dose-dependent antiviral activity against the virus. when used prophylactically (1 hour before exposure to the virus) in subtoxic doses, myramistin was effective in inhibiting replication of the influenza virus [strains a/aichi/2/68 (h3n2) and a/chicken/suzdalka/nov-11/2005 (h5n1)]. in urgent prophylaxis (1 hour after exposure to the virus) the protective effect was less pronou ...	2005	19140480
[emergence of new viruses in asia: is climate change involved?].	tropical africa is not the only area where deadly viruses have recently emerged. in south-east asia severe epidemics of dengue hemorrhagic fever started in 1954 and flu pandemics have originated from china such as the asian flu (h2n2) in 1957, the hong-kong flu (h3n2) in 1968, and the russian flu (h1n1) in 1977. however, it is especially during the last ten years that very dangerous viruses for mankind have repeatedly developed in asia, with the occurrence of alkhurma hemorrhagic fever in saudi ...	2004	15620053
[safety and immunogenicity of split vaccines of influenza viruses].	to evaluate the safety and immunogenicity of influenza split vaccine.	2004	15640848
[application of fluorescent real-time reverse transcriptase-polymerase chain reaction in detecting influenza viruses].	to apply fluorescent real-time reverse transcriptase-polymerase chain reaction (rt-pcr) in detecting influenza viruses.	2004	15640871
h3n2 influenza virus transmission from swine to turkeys, united states.	in 1998, a novel h3n2 reassortant virus emerged in the united states swine population. we report the interspecies transmission of this virus to turkeys in two geographically distant farms in the united states in 2003. this event is of concern, considering the reassortment capacity of this virus and the susceptibility of turkey to infection by avian influenza viruses. two h3n2 isolates, a/turkey/nc/16108/03 and a/turkey/mn/764/03, had 98.0% to 99.9% nucleotide sequence identity to each other in a ...	2004	15663853
antibodies to human-related h3 influenza a virus in baikal seals (phoca sibirica) and ringed seals (phoca hispida) in russia.	antibodies to influenza a virus were detected using enzyme-linked immunosorbent assay (elisa) in the sera from two of seven baikal seals (phoca sibrica) and from five of six ringed seals (phoca hispida) in russia. in a hemagglutination-inhibition test using h1-h15 reference influenza a viruses, elisa-positive sera from one baikal seal and four ringed seals reacted to a/aichi/2/68 (h3n2) and a/bangkok/1/79 (h3n2) strains. one ringed seal serum sample reacted to a/seal/massachusetts/1/80 (h7n7). t ...	2004	15557750
neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in mdck cells.	there is insufficient information about combination therapy with approved anti-influenza agents. we tested combinations that paired a neuraminidase (na) inhibitor (zanamivir, oseltamivir carboxylate, or peramivir) with rimantadine against infection of mdck cells with h1n1 and h3n2 subtypes of influenza a virus and characterized their mode of interaction. when reduction of extracellular virus was analyzed by individual regression models and three-dimensional representations of the data, all three ...	2004	15561867
induction of interferon-inducible protein-10 and monokine induced by interferon-gamma from human endothelial cells infected with influenza a virus.	primary human umbilical vein endothelial cells (huvecs) were infected with influenza virus a/aichi/2/68 (h3n2) in order to determine the role of endothelial cells in mediating inflammation induced upon virus infection. structural proteins of the virus and mrna of the m2 protein were detected in the infected cells, indicating that virus infection had occurred in huvecs. the influenza a virus-infected huvecs showed elevated levels of gene expression of interferon (ifn)-inducible protein (ip)-10 an ...	2004	14689273
influence of antigenic drift on the intensity of influenza outbreaks: upper respiratory tract infections of military conscripts in finland.	a total of 102,600 upper respiratory infections (uri) were recorded among young military conscripts in the finnish defence forces during the study period from october 1991 to march 1994. this period covered three outbreaks caused by h3n2-subtype influenza a virus and one outbreak of influenza b. during the 1991/92 outbreak caused by a/beijing/353/89-like virus, the calculated influenza a incidence was 2,206/10,000 men. during the 1992/93 outbreak when influenza b was the predominant virus, a new ...	2004	14695670
direct and total effectiveness of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine against the 2000-2001 influenza a(h1n1) and b epidemic in healthy children.	the efficacy of the intranasal, live-attenuated, trivalent cold-adapted influenza virus vaccine (caiv-t) against influenza a(h3n2) and b infections in healthy persons is established, but its effectiveness against natural influenza a(h1n1) infection is unknown.	2004	14706961
genetic analysis of human h2n2 and early h3n2 influenza viruses, 1957-1972: evidence for genetic divergence and multiple reassortment events.	phylogenic analysis of all gene segments of human h2n2 viruses isolated from 1957 to 1968 was undertaken to better understand the evolution of this virus subtype. human h3n2 viruses isolated from 1968 to 1972 were also examined to investigate genetic events associated with their emergence in humans and to identify the putative h2n2 ancestral virus. all gene segments of human h2n2 viruses demonstrated divergent evolution into two distinct clades (i and ii) among late h2n2 isolates. all gene segme ...	2004	15380362
surfactant vesicle-mediated delivery of dna vaccines via the subcutaneous route.	compared to naked dna immunisation, entrapment of plasmid-based dna vaccines into liposomes by the dehydration-rehydration method has shown to enhance both humoural and cell-mediated immune responses to encoded antigens administered by a variety of routes. in this paper we have compared the potency of lipid-based and non-ionic surfactant based vesicle carrier systems for dna vaccines after subcutaneous immunisation. plasmid pi.18sfi/np containing the nucleoprotein (np) gene of a/sichuan/2/87 (h3 ...	2004	15454294
[pulmonary cell susceptibility in mice and rats to influenza virus when infected in vivo and in vitro].	the purpose of the case study was to evaluate comparatively the relative contribution of cell susceptibility and the inhibiting effect of factors of pulmonary epithelial lining in mice and rats to influenza virus a/aichi/2/68 (h3n2) adapted to mice as related with the development of infection process in the lungs of experimental animals when infected in vivo and in vitro. mice and rats were infected aerogenically with different doses of influenza virus. the primary cell-culture suspensions sampl ...	2004	15455685
immunogenicity and tolerability of a trivalent virosomal influenza vaccine in a cohort of hiv-infected children.	twenty-three children infected with the human immunodeficiency virus (hiv) were vaccinated with a trivalent inactivated virosomal influenza vaccine. serum haemagglutinin inhibition antibody titres were determined for the three viral strains at the time of vaccination and 1 month later. cd4 cell counts and hiv viral loads were measured to evaluate the effect of vaccination on hiv status. adverse reactions were monitored during the first hour following vaccination by an investigator and then on a ...	2004	15458281
annual report of the national influenza surveillance scheme, 2003.	surveillance of influenza in australia is based on laboratory isolation of influenza viruses, sentinel general-practitioner practices for influenza-like illness, and absenteeism data from a major national employer. in 2003, the peak in influenza activity was in august which was later than in 2002. in 2003, 3,604 laboratory-confirmed cases of influenza were notified to the national notifiable diseases surveillance system, which was marginally lower than for the previous year. ninety-four per cent ...	2004	15460951
higher than normal seasonal influenza activity in victoria, 2003.	influenza surveillance in victoria comprises surveillance of patients with influenza-like illness (ili) from sentinel general practices and laboratory based reporting of influenza detections, predominantly from hospital inpatients. surveillance of patients with ili seen by the melbourne medical locum service (mmls) was conducted for the first time in 2003, when the influenza season was characterised by a late onset with higher than normal seasonal activity. influenza a (h3n2) was the predominant ...	2004	15460953
influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets.	three type a influenza viruses, each of which has a distinct neuraminidase-gene mutation and is resistant to the neuraminidase inhibitor oseltamivir, have been isolated. previously, in the ferret model, an r292k mutant of a type a (h3n2) virus was not transmitted under conditions in which the wild-type virus was transmitted. this model was used to investigate whether the e119v mutant of a type a (h3n2) virus and the h274y mutant of a type a (h1n1) virus would be transmitted under similar circums ...	2004	15478068
[screening for antibodies against zoonotic agents among employees of the zoological garden of vienna, schönbrunn, austria].	the aim of this study was to investigate the prevalence of antibodies against zoonotic agents in employees of the zoological garden of vienna, schönbrunn, austria. sixty out of 120 employees participated in the study. in 97% of them antibodies to at least one zoonotic agent were identified. only two participants were free of antibodies to the zoonotic agents tested. the following seroprevalences (in brackets) were obtained: viral zoonotic (and potentially zoonotic) agents: influenzavirus a/h1n1 ...	2004	15495931
no apoptotic deaths and different levels of inductions of inflammatory cytokines in alveolar macrophages infected with influenza viruses.	influenza viruses are reported to infect mainly the respiratory tract epithelium of hosts. our studies in a pig model show that influenza a viruses infect alveolar macrophages that constitutively reside in the respiratory tract, without causing apoptosis. tumor necrosis factor alpha was the inflammatory cytokine most highly induced in these macrophages. in vivo, alveolar macrophages infected with human h3n2 influenza virus showed greater expression of tumor necrosis factor alpha than did alveola ...	2004	15518807
[the 2003/2004 influenza season in the netherlands with a limited epidemic of the virus variant a/fujian, and the vaccine composition for the 2004/2005 season].	in contrast to the three previous influenza seasons, the influenza epidemic of the 2003/2004 season started early in week 49 of 2003. the epidemic was predominantly caused by influenza-a viruses of the h3n2 subtype. all isolated influenza-a viruses were antigenically related to influenza virus a/fujian/411/02, which was already detected in the influenza season 2002/2003 and that deviated from the vaccine-reference strain a/moscow/10/99 to a certain extent. the magnitude of the epidemic was limit ...	2004	15524136
treatment of mannan-enhanced influenza b virus infections in mice with oseltamivir, ribavirin and viramidine.	mannan, a polysaccharide preparation from saccharomyces cerevisiae, has previously been shown to enhance influenza virus replication in mice by inhibiting host defense collectins. the use of mannan in infections may serve to broaden the types of influenza viruses that can be studied in rodent infection models. when mannan was co-administered with influenza b/sichuan/379/99 virus to mice, the animals died from the infection, whereas mice infected with only virus survived. three types of influenza ...	2004	15535048
epidemiological features of a new strain of the influenza a virus--influenza a (h1n2) circulating in england and its public health implications.	the uk influenza season of 2001/2002 was characterized by widespread geographic circulation of a new subtype of influenza a (h1n2) virus throughout the duration of the season. younger children were predominantly infected, suggesting primary infection. despite this, the public health impact of this new virus was minimal. it remains to be seen whether influenza a (h1n2) virus will persist and co-circulate with the previously circulating subtypes of influenza a (h1n1 and h3n2), or whether it was a ...	2004	15163488
reassortment and evolution of current human influenza a and b viruses.	during the 2001-2002 influenza season, human influenza a (h1n2) reassortant viruses were detected globally. the hemagglutinin (ha) of these h1n2 viruses was similar to that of the a/new caledonia/20/99 (h1n1) vaccine strain both antigenically and genetically, while their neuraminidase (na) was antigenically and genetically related to that of recent human influenza h3n2 reference viruses such as a/moscow/10/99. all six internal genes of the h1n2 reassortants originated from an h3n2 virus. after b ...	2004	15163489
multiple lineages of antigenically and genetically diverse influenza a virus co-circulate in the united states swine population.	before the isolation of h3n2 viruses in 1998, swine influenza in the united states was an endemic disease caused exclusively by classical-swine h1n1 viruses. in this study we determined the antigenic and phylogenetic composition of a selection of currently circulating strains and revealed that, in contrast to the situation pre-1998, the swine population in the united states is now a dynamic viral reservoir containing multiple viral lineages. h3n2 viruses still circulate and representatives of ea ...	2004	15163491
genetic relationships, serological cross-reaction and cross-protection between h1n2 and other influenza a virus subtypes endemic in european pigs.	this study examines the genetic relationships between the recently emerged h1n2 swine influenza virus and viruses of h1n1 and h3n2 subtypes, and the extent of protection against h1n2 challenge in pigs immune after infection or vaccination with the other subtypes. there was low amino acid homology (70.4-71.9%) in the haemagglutinin (ha) gene between h1n1 viruses used for primary infection or vaccination and the h1n2 challenge strain, with 94-99 amino acid changes between these viruses involving a ...	2004	15163499
current status of live attenuated influenza virus vaccine in the us.	the efficacy and effectiveness of cold adapted live attenuated (caiv-t, flumist intranasal influenza vaccine is reviewed. caiv-t consists of approximately 10(7) tcid50 per dose of each influenza a/h1n1, influenza a/h3n2, and influenza b vaccine strain. the exact strains are updated each year to antigenically match the antigens recommended by national health authorities for inclusion in the vaccine. in one year in which the vaccine strain did not well match the epidemic strain, the live attenuate ...	2004	15163507
live cold-adapted influenza a vaccine produced in vero cell line.	the african green monkey kidney (vero) cell line was used as a substrate for the development of a live cold-adapted (ca) reassortant influenza vaccine. for that purpose, a new master strain was generated by an adaptation of the wild type (wt) a/singapore/1/57 virus to growth at 25 degrees c in a vero cell line. the resulting cold-adapted (ca) muster strain a/singapore/1/57ca showed temperature sensitive (ts) phenotype and was attenuated in animal models and protective in the challenge experiment ...	2004	15163508
prevention and control of influenza: recommendations of the advisory committee on immunization practices (acip).	this report updates the 2003 recommendations by the advisory committee on immunization practices (acip) on the use of influenza vaccine and antiviral agents (cdc. prevention and control of influenza: recommendations of the advisory committee on immunization practices [acip]. mmwr 2003;52[no. rr-8]:1-34). the 2004 recommendations include new or updated information regarding 1) influenza vaccine for children aged 6-23 months; 2) vaccination of health-care workers with live, attenuated influenza va ...	2004	15163927
[influenza viruses which preconditioned the epidemic rise in russia in 2002-2003. a resumed circulation of influenza viruses similar to v/victoria/2/87].	according to research, the epidemic rise of influenza was preconditioned, during 2002-2003, in russia by the circulation of influenza a(h1n1), a(h3n2) and b viruses. the center of influenza ecology and epidemiology undertook a study of 178 epidemic strains: 41 strains a(h1n1), 116 strains a(h3n2) and 21 strains of influenza b were among them. all strains were isolated in the mdck cell culture. a simultaneous isolation in embryonated eggs as well as changing of the isolation system from mdck to e ...	2004	15188649
amino-acid change on the antigenic region b1 of h3 haemagglutinin may be a trigger for the emergence of drift strain of influenza a virus.	sera from 27 children and eight older persons, which had been collected in 1998 and 1999 and showed haemagglutination-inhibition (hi) activity against influenza a/sydney/5/97 (h3n2) strain, were characterized with a binding assay using chimeric haemagglutinin (ha) proteins between a/aichi/2/68 (a/ai/68) and a/sydney/5/97 (a/sd/97) strains. sera from the young children had a tendency to recognize only the antigenic site b1 of the ha1 region. on the other hand, sera of the older individuals were f ...	2004	15188708
molecular epidemiology of porcine h3n2 influenza a viruses isolated in germany between 1982 and 2001.	we examined influenza virus strains of the subtype h3n2 from outbreaks of respiratory diseases in swine herds in germany. four different clusters can be distinguished when comparing parts of the ha1 gene from porcine h3n2 isolates analyzed between 1982 and 2001. comparison between these clusters reveals a bp homology of less than 90%. in contrast, the homology within the clusters is between 93.7 and 100%. each of these clusters was confined to a specific time period. for the na gene an additiona ...	2004	15192270
immunity to influenza in older adults with chronic obstructive pulmonary disease.	chronically ill older adults constitute a population vulnerable for complications associated with influenza. study of their immunity to influenza virus may help design better strategies to stimulate protective immune responses.	2004	15195238
influenza a virus pb1-f2 gene in recent taiwanese isolates.	influenza a virus contains eight rna segments and encodes 10 viral proteins. however, an 11th protein, called pb1-f2, was found in a/puerto rico/8/34 (h1n1). this novel protein is translated from an alternative open reading frame (orf) in the pb1 gene. we analyzed the pb1 gene of 42 recent influenza a isolates in taiwan, including 24 h1n1 and 18 h3n2 strains. one h1n1 isolate and 17 h3n2 isolates contained the entire pb1-f2 orf of 90 residues, three amino acids (aa) longer than the pb1-f2 of a/p ...	2004	15200852
evolutional analysis of human influenza a virus n2 neuraminidase genes based on the transition of the low-ph stability of sialidase activity.	the 1957 and 1968 human pandemic influenza a virus strains as well as duck viruses possess sialidase activity under low-ph conditions, but human h3n2 strains isolated after 1968 do not possess such activity. we investigated the transition of avian (duck)-like low-ph stability of sialidase activities with the evolution of n2 neuraminidase (na) genes in human influenza a virus strains. we found that the na genes of h3n2 viruses isolated from 1971 to 1982 had evolved from the side branches of na ge ...	2004	14741372
generation of high-yielding influenza a viruses in african green monkey kidney (vero) cells by reverse genetics.	influenza a viruses are the cause of annual epidemics of human disease with occasional outbreaks of pandemic proportions. the zoonotic nature of the disease and the vast viral reservoirs in the aquatic birds of the world mean that influenza will not easily be eradicated and that vaccines will continue to be needed. recent technological advances in reverse genetics methods and limitations of the conventional production of vaccines by using eggs have led to a push to develop cell-based strategies ...	2004	14747549
comparison of a commercial enzyme-linked immunosorbent assay with hemagglutination inhibition assay for serodiagnosis of swine influenza virus (h1n1) infection.	a commercial indirect swine influenza virus (siv) h1n1 enzyme-linked immunosorbent assay (elisa) was compared with the hemagglutination inhibition (hi) assay by testing 72 samples from experimentally infected pigs and 780 field samples of undefined siv status. the hi assay was performed using siv isolates a/swine/ia/73 for h1n1 and a/swine/ia/8548-1/98 for h3n2. the elisa used an siv isolated in 1988. the results showed that hi and elisa detected an antibody in 11 and 6, respectively, of 72 seru ...	2004	14974854
transmission of h7n7 avian influenza a virus to human beings during a large outbreak in commercial poultry farms in the netherlands.	an outbreak of highly pathogenic avian influenza a virus subtype h7n7 started at the end of february, 2003, in commercial poultry farms in the netherlands. although the risk of transmission of these viruses to humans was initially thought to be low, an outbreak investigation was launched to assess the extent of transmission of influenza a virus subtype h7n7 from chickens to humans.	2004	14987882
design of n-acetyl-6-sulfo-beta-d-glucosaminide-based inhibitors of influenza virus sialidase.	biological activity of n-acetyl-6-sulfo-beta-d-glucosaminides (6-sulfo-glcnac 1) having a structural homology to n-acetylneuraminic acid (neu5ac 2) and 2-deoxy-2,3-dehydro-n-acetylneuraminic acid (neu5ac2en 3) was examined in terms of inhibitory activity against influenza virus sialidase (influenza, a/memphis/1/71 h3n2). pnp 6-sulfo-glcnac 1a was proved to show substantial activity to inhibit the virus sialidase (ic(50)=2.8 mm), though p-nitrophenyl (pnp) glcnac without 6-sulfo group and pnp 6-s ...	2004	15018909
[evaluation of influenza vaccine vaxigrip in the combined immunization of conscripts during influenza seasons of 2002-2003].	the immunization properties of the influenza vaccine vaxigrip, used in combination with vaccines against pneunococcal infection and hepatitis a (respectively, pneumo 23 and avaxim), were evaluated. in central russia in one of the units of the internal forces of the rf ministry of internal affairs 3 groups totaling 755 servicemen were formed, depending on the complex of the introduced vaccines. active medical observation and the registration of the complaints of the vaccinees at the postvaccinal ...	2004	15024982
evaluation of transmission of swine influenza type a subtype h1n2 virus in seropositive pigs.	to examine clinical signs, virus infection and shedding, and transmission of swine influenza virus (siv) subtype h1n2 among seropositive pigs.	2004	15027676
changes in in vitro susceptibility of influenza a h3n2 viruses to a neuraminidase inhibitor drug during evolution in the human host.	influenza a h3n2 viruses isolated recently have characteristic receptor binding properties that may decrease susceptibility to neuraminidase inhibitor drugs. a panel of clinical isolates and recombinant viruses generated by reverse genetics were characterized and tested for susceptibility to zanamivir.	2004	15028666
rapid detection and simultaneous subtype differentiation of influenza a viruses by real time pcr.	a real time rt-pcr, using the lightcycler, was developed and compared with rapid antigen enzyme immunoassay (ageia) and enhanced virus culture for rapid detection of influenza a viruses in stored and prospectively collected respiratory specimens. specific hybridization probes were used for simultaneous detection and differentiation between h1n1 and h3n2 subtypes. the sensitivity of the rt-pcr for influenza a h1n1 was 120 copies and h3n2 350 copies of in vitro transcribed rna. a specimen was cons ...	2004	15041206
antigenic and molecular analysis of influenza a (h3n2) virus strains isolated from a localised influenza outbreak in south africa in 2003.	a severe acute institutional influenza outbreak occurred in a police residential college in pretoria amongst new recruits and staff members at the end of may 2003. the outbreak was characterised by marked illness which affected a total of 648 students, 26 of whom were admitted to hospital. symptoms included pyrexia, severe headache, and myalgia. the attack rate per dormitory building ranged from 20 to 47%, with an overall attack rate of 34%. throat swabs and bronchoalveolar lavage specimens were ...	2004	15042651
cold-adapted, live attenuated influenza vaccine.	the recently licensed cold-adapted, live attenuated influenza vaccine (caiv-t, flumist, medimmune vaccines inc.) has the potential to enhance control of epidemic influenza. the intranasal vaccine has proven safety and efficacy. regulatory constraints and cost of caiv-t have hampered the introduction of the vaccine in the first year. unwarranted concern about possible transmission of the virus from vaccine recipients to immunocompromised patients limited use in healthcare personnel. the intense i ...	2004	15056039
detection of avian paramyxoviruses and influenza viruses amongst wild bird populations in victoria.	to isolate and characterise avian paramyxoviruses and other haemagglutinating viruses amongst victorian wild bird populations.	2004	15088965
structural and functional analysis of glycosylated cu/zn-superoxide dismutase from the fungal strain humicola lutea 103.	the fungal strain humicola lutea 103 produces a naturally glycosylated cu/zn-superoxide dismutase (cu/znsod) (hlsod). to improve its yield, the effect of increased concentration of cu2+ (from 1 to 750 microg/ml) on growth and enzyme biosynthesis was studied. the primary structure of this fungal enzyme has been determined by edman degradation of peptide fragments derived from proteolytic digest. a single chain of the protein, consisting of 152 amino acid residues, reveals a very high degree (74-8 ...	2004	15094369
[an analysis of the 2002-2003 influenza epidemic focusing on patients infected with types a and b in the same season sequentially].	a total of 2,320 cases of influenza a (1,517 cases) and b (803 cases) in the 2002-2003 influenza season were analyzed. influenza infection was confirmed by a rapid diagnosis kit, based on the immunochromatography method, at 24 clinics in 18 of the 47 prefectures of japan. influenza a/h3n2 was reported between november 22 and april 12 (the median at january 21), and influenza b was reported between december 24 and april 20 (the median at february 16). the mean age of type b patients (16.7 years o ...	2004	15103903
influenza-induced tachypnea is prevented in immune cotton rats, but cannot be treated with an anti-inflammatory steroid or a neuraminidase inhibitor.	influenza viruses are one of the leading causes of morbidity and mortality during winter months. increased respiratory rate (tachypnea) is a sign of increasing lower respiratory disease during influenza infection and is frequently observed in hospitalized patients. we investigated this clinical sign in influenza virus-infected cotton rats (sigmodon hispidus) and the efficacy of antiviral and anti-inflammatory therapy in reducing symptomatic disease. cotton rats infected intranasally with a/wuhan ...	2004	15110527
use of the dna flow-thru chip, a three-dimensional biochip, for typing and subtyping of influenza viruses.	influenza a viruses, which are further subtyped on the basis of antigenic differences in external hemagglutinin and neuraminidase glycoproteins, and influenza b viruses are prominent among the viral causes of respiratory diseases and can cause a wide spectrum of illness. each year these viruses are responsible for recurrent epidemics, frequently in association with genetic variation. there is a requirement for sensitive and rapid diagnostic techniques in order to improve both the diagnosis of in ...	2004	15131186
moderate exercise improves antibody response to influenza immunization in older adults.	influenza vaccine efficacy is reduced among adults over age 65 and a significant number of vaccinated elderly may remain susceptible to influenza virus infection. the effect of moderate exercise training on the immune response to influenza immunization was evaluated in this study. twenty-seven adults >or=age 64 were assigned to an exercise group (n= 14) or a control group (n = 13). the subjects exercised at 65-75% heart rate reserve (hrr), 25-30 min, 3 days per week, for 10 months. controls did ...	2004	15149789
comparison of a commercial h1n1 enzyme-linked immunosorbent assay and hemagglutination inhibition test in detecting serum antibody against swine influenza viruses.	recently a commercial enzyme-linked immunosorbent assay (elisa) kit for detecting antibody against h1n1 swine influenza virus (siv) has been made available to diagnosticians and veterinary practitioners. because the hemagglutination inhibition (hi) test has been considered the standard test for siv serology, diagnostic performance of the new elisa was evaluated using positive (n = 60) and negative (n = 188) serum samples from young pigs with known status of siv infection and compared with that o ...	2004	15152833
influenza a viruses possessing type b hemagglutinin and neuraminidase: potential as vaccine components.	a licensed live attenuated influenza vaccine is available as a trivalent mixture of types a (h1n1 and h3n2) and b vaccine viruses. thus, interference among these viruses could restrict their replication, affecting vaccine efficacy. one approach to overcoming this potential problem is to use a chimeric virus possessing type b hemagglutinin (ha) and neuraminidase (na) in a type a vaccine virus background. we previously generated a type a virus possessing a chimeric ha in which the entire ectodomai ...	2004	15158192
mapping the antigenic and genetic evolution of influenza virus.	the antigenic evolution of influenza a (h3n2) virus was quantified and visualized from its introduction into humans in 1968 to 2003. although there was remarkable correspondence between antigenic and genetic evolution, significant differences were observed: antigenic evolution was more punctuated than genetic evolution, and genetic change sometimes had a disproportionately large antigenic effect. the method readily allows monitoring of antigenic differences among vaccine and circulating strains ...	2004	15218094
[influenza in poland in 2002].	in 2002 the number of cases of influenza and influenza-like illness (ili) registered in poland amounted to 228,055. this is 39.5% of the number of cases recorded in 2001. the highest influenza incidence was found in mazowieckie voivodship (2297.5 per 100,000), while the lowest incidence was registered in swietokrzyskie voivodship (104.1) and lubelskie voivodship (117.6). in children aged 0 to 14 years the number of influenza and ili cases amounted to 104,552 (incidence of 1511.9 per 100,000) and ...	2004	15218642
update: influenza activity--united states and worldwide, 2003-04 season, and composition of the 2004-05 influenza vaccine.	during the 2003-04 influenza season, influenza a (h1), a (h3n2), and b viruses co-circulated worldwide, and influenza a (h3n2) viruses predominated. several asian countries reported widespread outbreaks of avian influenza a (h5n1) among poultry. in vietnam and thailand, these outbreaks were associated with severe illnesses and deaths among humans. in the united states, the 2003-04 influenza season began earlier than most seasons, peaked in december, was moderately severe in terms of its impact o ...	2004	15229411
new estimates of influenza-related pneumonia and influenza hospitalizations among the elderly.	the aim of this study is to present a method to provide accurate estimates of influenza-associated pneumonia and influenza (p&i) hospitalizations and costs for use in tracking the continuing burden of influenza.	2004	15234327
total viral genome copies and virus-ig complexes after infection with influenza virus in the nasal secretions of immunized mice.	the kinetics of infectious virus (p.f.u.), total virus and virus-ig complex formation following influenza a/pr8 (h1n1) viral infection was examined in the nasal secretions of naive mice and mice immunized with a/pr8, a/yamagata (h1n1), a/guizhou (h3n2) and b/ibaraki influenza viruses. the total number of virus particles and the number within virus-ig complexes, captured in advance using an anti-mouse ig-coated plate, were determined on the basis of viral genome copy number using quantitative rt- ...	2004	15269375
cytokine induction in human cord blood lymphocytes after pulsing with uv-inactivated influenza viruses.	mitogenic activity of uv-inactivated influenza viruses in cord blood lymphocytes (cbl), as measured by cytokine release, was investigated. using prototype viruses of subtype h3n2 (a/aichi/68), h2n2 (a/japan/57), and h1n1 (a/puerto rico/34) for influenza a virus, and b/lee/40 for influenza b virus, the results indicated that both th1 and th2 cytokines were induced. stimulation indices were significantly higher for ifngamma, il-4 and il-10 by influenza a viruses than by influenza b virus. stimulat ...	2004	15275967
[influenza c virus isolated in hiroshima prefecture during the 1999/2000 winter season--a clinical and epidemiological study].	influenza c virus (inf. c) is one of pathogens of human respiratory tract infection and prevalent throughout the world at an early stage in life. however, inf. c has been isolated only accidentally and there have been few reports on its clinical and epidemiological features. from november 1999 to march 2000, inf. c was isolated from clinical specimens (throat swabs) of 4 pediataric patients with respiratory tract illness at hiroshima prefectural hospital and was isolated in 4 peditaric patients ...	2004	15287473
adaptation and limitations of established hemagglutination inhibition assays for the detection of porcine anti-swine influenza virus h1n2 antibodies.	hemagglutination inhibition (hi) has been a reliable method for determining porcine antibody levels to the well-characterized swine influenza virus (siv) h1n1 and h3n2 subtypes. however, the recent emergence of the novel h1n2 serotype of siv and the persistence of 2 other serotypes (h1n1 and h3n2) in the united states swine population represents a significant challenge to diagnostics. both standardized and modified hi protocols were used in a blinded study to examine a collection of 50 control s ...	2004	15305735
assessment of the effectiveness of the 2003-04 influenza vaccine among children and adults--colorado, 2003.	the 2003-04 influenza season was characterized by the early onset of influenza activity, reports of severe illness, particularly in children, and predominant circulation of an influenza a (h3n2) virus strain that was antigenically different from the influenza a (h3n2) vaccine strain. in 2003, a retrospective cohort study among children and a case-control study among adults in colorado were conducted to provide preliminary data on the effectiveness of the 2003-04 influenza vaccine. this report su ...	2004	15306754
protection of weaned pigs by vaccination with human adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of h3n2 swine influenza virus.	swine influenza virus (siv), subtype h3n2, is a recent reassortant virus that emerged in 1998 in north american swine causing severe respiratory and reproductive disease. in this study, two replication-defective adenovirus recombinants were developed as potential vaccines against h3n2 influenza viruses. three groups of 3-week-old pigs (10 pigs per group) were vaccinated intramuscularly (im) with the recombinants; one group was vaccinated with the recombinant adenovirus expressing the influenza v ...	2004	15308368
influenza and the winter increase in mortality in the united states, 1959-1999.	in economically developed countries, mortality increases distinctly during winter. many causes have been suggested, including light-dark cycles, temperature/weather, and infectious agents. the authors analyzed monthly mortality in the united states during the period 1959-1999 for four major disease classes. the authors isolated the seasonal component of mortality by removing trends and standardizing the time series. they evaluated four properties: coincidence in mortality peaks, autocorrelation ...	2004	15321847
effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza a/h3n2 virus hemagglutinin.	influenza a/h3n2 viruses have developed an increased number of glycosylation sites on the globular head of the hemagglutinin (ha) protein since their appearance in 1968. here, the effect of addition of oligosaccharide chains to the ha of a/h3n2 viruses on its biological activities was investigated. we constructed seven mutant has of a/aichi/2/68 virus with one to six glycosylation sites on the globular head, as found in natural isolates, by site-directed mutagenesis and analyzed their intracellu ...	2004	15331693
resistant influenza a viruses in children treated with oseltamivir: descriptive study.	oseltamivir is an effective inhibitor of influenza virus neuraminidase. although viruses resistant to oseltamivir emerge less frequently than those resistant to amantadine or rimantadine, information on oseltamivir-resistant viruses arising during clinical use of the drug in children is limited. our aim was to investigate oseltamivir resistance in a group of children treated for influenza.	2004	15337401
[antigenic and genetic characterizations of group a influenza viruses h3n2 circulated in men in china during 2000-2002].	to understand the antigenic and genetic characteristics of influenza a h3n2 viruses circulated in man in china from 2000 to 2002.	2004	15340518
exposure of sero-positive gilts to swine influenza virus may cause a few stillbirths per litter.	six pregnant gilts were purchased from a high health herd and were found to be serologically positive for swine influenza virus (siv) subtype h3n2. three of the gilts, at 80 to 82 days of gestation, were experimentally exposed a second time to the same siv subtype--h3n2. no clinical signs resulted from the second exposure to siv and hemagglutination-inhibition (hi) titers for siv at 4 weeks postexposure were unchanged suggesting that the gilts had not been reinfected. however, the second exposur ...	2004	15352547
influenza surveillance in indonesia: 1999-2003.	although influenza is recognized for its worldwide importance, little is known about the disease from tropical countries like indonesia. from august 1999 through january 2003, a surveillance study was conducted in clinics at 6 sentinel locations. adults (age, >14 years) and children (age, 4-14 years) presenting with respiratory symptoms suggestive of influenza were asked to enroll in the study. nasal and pharyngeal swabs were examined by virus isolation, polymerase chain reaction, and rapid immu ...	2004	15356802
detection and control of influenza outbreaks in well-vaccinated nursing home populations.	influenza outbreaks continue to occur in nursing homes despite high vaccination coverage among residents. recommendations for outbreak control in institutions such as nursing homes advises use of antiviral drugs to reduce influenza transmission.	2004	15356805
measuring antibody responses to a live attenuated influenza vaccine in children.	hemagglutination inhibition (hai) assay is the standard method for evaluating inactivated influenza vaccines, but no standard assay has been established for evaluating live attenuated influenza vaccines (laiv). laiv containing a/beijing/262/95(h1n1) induced low serum hai antibody responses to the antigenic variant, a/new caledonia/20/99(h1n1) in a serologic study but provided protection against the a/new caledonia-like viruses in a community study. neutralization and hai assays were compared by ...	2004	15361726
influenza circulating strains in argentina exhibit differential induction of cytotoxicity and caspase-3 in vitro.	human influenza infections are a significant cause of morbidity worldwide. though damage to the respiratory epithelium and has been related to apoptosis, which occurs subsequent to influenza virus infection, little information is available regarding cell cytotoxicity of human strains.	2004	15364270
influenza-associated hospitalizations in the united states.	respiratory viral infections are responsible for a large number of hospitalizations in the united states each year.	2004	15367555
[survey research of serum anti-influenza virus antibody levels in chinese young people during 1997-2000].	to survery the levels of serum anti-influenza virus antibodies and variable extent of the virus in the young people.	2003	15163386
efficacy trial of live, cold-adapted and inactivated influenza virus vaccines in older adults with chronic obstructive pulmonary disease: a va cooperative study.	we assessed whether trivalent live, cold-adapted influenza virus (caiv-t) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (tvv) in patients with chronic obstructive pulmonary disease (copd). subjects (n=2215) were randomly assigned to receive either tvv intramuscularly (im) and caiv-t intranasally (tc), or tvv and placebo (tp). the vaccines were well-tolerated. efficacy of tc compared to tp was not statistically significant and was 0.16 f ...	2003	12706704
differential requirements of rab5 and rab7 for endocytosis of influenza and other enveloped viruses.	enveloped viruses often enter cells via endocytosis; however, specific endocytic trafficking pathway(s) for many viruses have not been determined. here we demonstrate, through the use of dominant-negative rab5 and rab7, that influenza virus (influenza a/wsn/33 (h1n1) and a/x-31 (h3n2)) requires both early and late endosomes for entry and subsequent infection in hela cells. time-course experiments, monitoring viral ribonucleoprotein colocalization with endosomal markers, indicated that influenza ...	2003	12713661
comparison of the pathogenesis of two genetically different h3n2 influenza a viruses in pigs.	in 1997 and 1998, h3n2 influenza a viruses emerged among pigs in north america. genetic analyses of the h3n2 isolates demonstrated that they had distinctly different genotypes. the most commonly isolated viruses in the united states have a triple-reassortant genotype, with the hemagglutinin, neuraminidase, and pb1 polymerase genes being of human influenza virus origin, the nucleoprotein, matrix, and nonstructural genes being of classical swine influenza virus origin, and the pa and pb2 polymeras ...	2003	12734230
the comparison of antibody response to influenza vaccination in continuous ambulatory peritoneal dialysis, hemodialysis and renal transplantation patients.	the immune system in renal transplant (tx), continuous ambulatory peritoneal dialysis (capd) and hemodialysis (hd) patients have been suppressed and antibody response to vaccination is weaker than that of the normal population. additionally immune response to vaccination also differs from each other in aforementioned three groups resulting from different levels immunosuppression. in the present study, detection of antibody response to influenza vaccine as an indicator of the level of immunity in ...	2003	12745749
occurrence of influenza b/hong kong-like strains in brazil, during 2002.	through the influenza virus surveillance from january to october 2002, influenza b/hong kong-like strains circulating in the southeast and centre east regions of brazil have been demonstrated. this strain is a variant from b/victoria/02/88 whose since 1991 and until recently have been isolated relatively infrequently and have been limited to south-eastern asia. a total of 510 respiratory secretions were collected from patients 0 to 60 years of age, with acute respiratory illness, living in the s ...	2003	12751324
a molecular mechanism for the low-ph stability of sialidase activity of influenza a virus n2 neuraminidases.	four human pandemic influenza a virus strains isolated in 1957 and 1968, but not most of the epidemic strains isolated after 1968, possess sialidase activity under low-ph conditions. here, we used cell-expressed neuraminidases (nas) to determine the region of the n2 na that is associated with low-ph stability of sialidase activity. we found that consensus amino acid regions responsible for low-ph stability did not exist in pandemic nas but that two amino acid substitutions in the low-ph-stable a ...	2003	12753908
prevention and control of influenza. recommendations of the advisory committee on immunization practices (acip).	this report updates the 2002 recommendations by the advisory committee on immunization practices (acip) on the use of influenza vaccine and antiviral agents (cdc. prevention and control of influenza: recommendations of the advisory committee on immunization practices [acip]. mmwr 2002;51 [no. rr-3]:1-31). the 2003 recommendations include new or updated information regarding 1) the timing of influenza vaccination by age and risk group; 2) influenza vaccine for children aged 6-23 months; 3) the 20 ...	2003	12755288
protection and compensation in the influenza virus-specific cd8+ t cell response.	influenza virus-specific cd8+ t cells generally recognize peptides derived from conserved, internal proteins that are not subject to antibody-mediated selection pressure. prior exposure to any one influenza a virus (h1n1) can prime for a secondary cd8+ t cell response to a serologically different influenza a virus (h3n2). the protection afforded by this recall of established cd8+ t cell memory, although limited, is not negligible. key characteristics of primary and secondary influenza-specific h ...	2003	12775762
update: influenza activity--united states and worldwide, 2002-03 season, and composition of the 2003-04 influenza vaccine.	in collaboration with the world health organization (who), its collaborating laboratories, state and local health departments, health-care providers, and vital statistic registries, cdc conducts surveillance to monitor influenza activity and to detect antigenic changes in the circulating strains of influenza viruses. during the 2002-03 influenza season, influenza a (h1), a (h3n2), and b viruses co-circulated in the northern hemisphere. human infections with avian influenza a (h5n1) and a (h7n7) ...	2003	12803198
effect of vitamin e and vitamin c combination on experimental influenza virus infection.	successful antioxidant treatment of the so-called "free radical diseases" has been reported in the literature. in this study we examined the preventive effect of vitamin e and vitamin c, alone and in combination, on the damage caused by influenza virus infection (ivi). male mice (icr), infected with influenza virus a/2/68/(h3n2) (1.5 of ld(50)), were administered single once-daily doses of vitamin e (60 mg/kg b.w.) and vitamin c (80 mg/kg b.w.) intraperitoneally (3 days before virus inoculation) ...	2003	12808470
neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir.	the influenza virus neuraminidase (na) inhibitors zanamivir and oseltamivir were introduced into clinical practice in various parts of the world between 1999 and 2002. in order to monitor the potential development of resistance, the neuraminidase inhibitor susceptibility network was established to coordinate testing of clinical isolates collected through the world health organization influenza surveillance network from different regions of the world (m. zambon and f. g. hayden, antivir. res. 49: ...	2003	12821478
[avian influenza and oseltamivir; a retrospective view].	the outbreak of avian influenza a due to an h7n7 virus in dutch poultry farms turned out to have public-health effects for those who were involved in the management of the epidemic and who were thus extensively exposed to contaminated excreta and dust. an outbreak-management team (omt) of experts in virology, infectious diseases and public health advised the dutch government with respect to the potential health effects on humans. strict hygiene measures were advised. moreover, vaccination agains ...	2003	12822517
epidemiology and molecular characterization of co-circulating influenza a/h3n2 virus variants in children: houston, texas, 1997-8.	co-circulating variants of influenza a/h3n2 viruses in children were studied in houston, texas between october 1997 and march 1998 to assess the effects of a new variant strain on the severity of clinical illness. influenza a virus was isolated from the nasal wash or nasal aspirate specimens collected from children at two tertiary care hospitals, and 271 isolates were available for variant-specific subtyping using rt-pcr and restriction fragment length polymorphism (rflp) analysis. we classified ...	2003	12825738
combined protective effect of a fungal cu/zn-containing superoxide dismutase and rimantadine hydrochloride in experimental murine influenza a virus infection.	the combined protective effect of a novel naturally glycosylated cu/zn-containing superoxide dismutase, produced by the fungus humicula lutea (hl-sod) strain 103, and the selective anti-influenza drug rimantadine hydrochloride (rim) was evaluated in experimental virus infection in mice, induced with influenza virus a/aichi/2/68 (h3n2). a combined application of hl-sod and rim in doses, which by themselves did not protect significantly mice against the infection, resulted in a synergistically inc ...	2003	12828346
pathogenic and antigenic properties of phylogenetically distinct reassortant h3n2 swine influenza viruses cocirculating in the united states.	swine influenza is an acute respiratory disease caused by type a influenza viruses. before 1998, swine influenza virus isolates in the united states were mainly of the classical h1n1 lineage. since then, phylogenetically distinct reassortant h3n2 viruses have been identified as respiratory pathogens in pigs on u.s. farms. the h3n2 viruses presently circulating in the u.s. swine population are triple reassortants containing avian-like (pa and pb2), swine-like (m, np, and ns), and human-like (ha, ...	2003	12843064