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protective role of gamma interferon during the recall response to influenza virus.during secondary immune responses to influenza virus, virus-specific t memory cells are a major source of gamma interferon (ifn-gamma). we assessed the contribution of ifn-gamma to heterologous protection against the a/wsn/33 (h1n1) virus of wild-type and ifn-gamma-/- mice previously immunized with the a/hk/68 (h3n2) virus. the ifn-gamma-/- mice displayed significantly reduced survival rates subsequent to a challenge with various doses of the a/wsn/33 virus. this was associated with an impaired ...19989658110
increased susceptibility of diabetic mice to influenza virus infection: compromise of collectin-mediated host defense of the lung by glucose?the influence of diabetes on susceptibility to influenza virus infection was examined in a mouse model in which rip-kb transgenic mice and their nontransgenic littermates were used as the diabetic and nondiabetic hosts, respectively. influenza virus a/phil/82 (h3n2) grew to significantly higher titers in the lungs of diabetic than nondiabetic mice. the extent of viral replication in the lungs was proportional to blood glucose levels in the mice at the time of infection, and the enhanced suscepti ...19989658139
an antibody which binds to the membrane-proximal end of influenza virus haemagglutinin (h3 subtype) inhibits the low-ph-induced conformational change and cell-cell fusion but does not neutralize virus.a monoclonal antibody, lmbh6, was derived from mice which had been sequentially immunized with bromelain-cleaved haemagglutinin (bha) from influenza virus a/aichi/2/68, a/victoria/3/75 and a/philippines/2/82 (all h3n2). lmbh6 recognizes the haemagglutinin (ha) of all h3n2 influenza a strains tested, which were isolated between 1968 and 1989. ha in the low-ph-induced conformation is not recognized, and cleavage of the ha0 precursor to ha1 and ha2 is needed to obtain efficient binding. compared to ...19989680143
field investigation of influenza vaccine effectiveness on morbidity.our objective was to evaluate influenza vaccine effectiveness during an influenza epidemic by means of a matched case-control study. the study was performed by 35 general practitioners who collected specimens for influenza virus testing from 610 patients who consulted for infectious syndrome: 168 (28%) were influenza-positive. two designs were used for selecting controls to take into account the high incidence-rate of influenza-like illness and the various possible protective effects of the vacc ...19989682334
supplementation of conventional influenza a vaccine with purified viral neuraminidase results in a balanced and broadened immune response.influenza virus neuraminidase was chromatographically extracted from a/johannesburg/33/94 (h3n2) and used to supplement conventional monovalent h3jhn2jh inactivated influenza vaccine. immunization of mice with this preparation resulted in high titers of antibodies to both hemagglutinin (ha) and neuraminidase (na) equivalent for each antigen to titers in animals immunized with either antigen alone. homotypic infection was suppressed and greater reduction in viral replication was observed followin ...19989682352
natural and 'in vitro' selected antigenic variants of influenza a virus (h2n2).we provide data on the prevalence of srh antibody to influenza a/singapore/1/57 (h2n2). approximately 10.3% of sera had antibody to the influenza a (h2n2) subtype virus in comparison to the 36.9% of positive sera to a representative influenza a (h3n2) and 31.5% to influenza a (h1n1) viruses. the percentage of subjects with antibody constantly decreased from the older to the younger age groups. persons born after 1968 were essentially seronegative, whereas subjects born before 1900, and in the de ...19989733372
update: outbreak of influenza a infection--alaska and the yukon territory, july-august 1998.on july 26, 1998, cdc and health canada, in cooperation with local public health authorities, began investigating reports of febrile respiratory illnesses and associated pneumonia among summer land and sea travelers to alaska and the yukon territory (1). epidemiologic and laboratory evidence has implicated influenza a virus as the etiologic agent of the outbreak. from june 11 through august 22, completed viral cultures of 101 (48%) of 209 nasopharyngeal specimens have yielded 26 influenza a isol ...19989733414
multiplex pcr for typing and subtyping influenza and respiratory syncytial viruses.a multiplex reverse transcription (rt)-pcr method that has been developed is capable of detecting and subtyping influenza a (h1n1 and h3n2) and b viruses as well as respiratory syncytial virus (rsv) types a and b in respiratory clinical samples taken as part of a national community-based surveillance program of influenza-like illness in england and wales. the detection of each different pathogen depended on distinguishing five amplification products of different sizes on agarose gels following r ...19989738055
evolutionary characteristics of influenza b virus since its first isolation in 1940: dynamic circulation of deletion and insertion mechanism.new antigenic variants of b/yamagata/16/88-like lineage which appeared in the season of 1997 as a minor strain tended to predominate in the following season. also, we could observe for the first time, three peaks of activity caused by h3n2 virus and two variants of b influenza virus. antigenic and phylogenetic analyses revealed that b/victoria/2/87-like variants appeared again in japan in 1997 after a nine-year absence. influenza b viruses evolved into three major lineages, including the earlies ...19989739335
transfectant influenza a viruses are effective recombinant immunogens in the treatment of experimental cancer.using reverse genetics methods, we constructed three different transfectant influenza a viruses encoding an ld-restricted, nine amino-acid-long fragment, corresponding to amino-acid residues 876-884, of beta-galactosidase (beta-gal). sequences encoding this epitope were nested within the hemagglutinin (ha) or neuraminidase (na) open reading frames. alternatively, an independent beta-gal mini-gene, preceded by an endoplasmic reticulum insertion signal sequence, was placed in a bicistronic arrange ...19989740780
comparison of rna hybridization, hemagglutination assay, titration of infectious virus and immunofluorescence as methods for monitoring influenza virus replication in vitro.rapid and sensitive methods for the monitoring of influenza virus replication in vitro are needed to address several research questions. four methods based on different principles were compared: the hemagglutination (ha) assay, the measurement of virus infectivity titers in culture supernatants, the enumeration of infected cells by immunofluorescence and rna hybridization techniques using digoxigenin (dig) labeled rna probes. to this end, mdck cells were infected at different multiplicities of i ...19989763129
human cytotoxic t-lymphocyte repertoire to influenza a viruses.the murine cd8(+) cytotoxic-t-lymphocyte (ctl) repertoire appears to be quite limited in response to influenza a viruses. the ctl responses to influenza a virus in humans were examined to determine if the ctl repertoire is also very limited. bulk cultures revealed that a number of virus proteins were recognized in ctl assays. ctl lines were isolated from three donors for detailed study and found to be specific for epitopes on numerous influenza a viral proteins. eight distinct cd8(+) ctl lines w ...19989765409
a sensitive and specific elisa immunocapture assay for rapid quantitation of influenza a/h3n2 neuraminidase protein.both ha and na proteins elicit antibodies which have been shown to be capable of altering the course of infection. nevertheless, while influenza virus vaccine standardization involves hemagglutinin (ha) and neuraminidase (na) in terms of antigenic characterization, only ha protein quantitation is undertaken. an immunocapture elisa (eia) is described for n2 na quantitation, based on the use of a highly specific monoclonal antibody (mab) for capturing na and an anti-na antiserum for antigen detect ...19989766889
comparison of neutralizing and hemagglutination-inhibiting antibody responses to influenza a virus vaccination of human immunodeficiency virus-infected individuals.a neutralization enzyme immunoassay (n-eia) was used to determine the neutralizing serum antibody titers to influenza a/taiwan/1/86 (h1n1) and beijing/353/89 (h3n2) viruses after vaccination of 51 human immunodeficiency virus (hiv) type 1-infected individuals and 10 healthy noninfected controls against influenza virus infection. overall, the n-eia titers correlated well with the hemagglutination-inhibition (hai) titers that were observed in the same samples in a previous study (f. p. kroon, j. t ...19989455891
expression of rantes by normal airway epithelial cells after influenza virus a infection.the chemokine regulated on activation, normal t cells expressed and secreted (rantes), is a c-c chemokine and a potent chemoattractant for monocytes, t lymphocytes, basophils, and eosinophils. its expression by human airway epithelium has been demonstrated both in vitro and in vivo. we investigated whether rantes is expressed by normal human airway epithelial cells after influenza viral infection and examined its bioactivity. epithelial cells were obtained from bronchial tissue or nasal polyps o ...19989476913
[fast detection and characterization of influenza a and b viruses in nasopharyngeal secretions by the immunoperoxidase method].one hundred and fourty eight samples from patients with a symptomatology compatible with the influenza virus were studied aimed at identifying in a fast way these viruses. a rapid mdck-l cell culture was developed on 96 well plates, where nasopharingeal exudates or gargarisms were inoculated and incubated all night long at 37 degrees c. the medium was removed and cells were washed with pbs and fixed with methanol. viral antigens were detected through the immunoperoxidase staining by using two mo ...19989842266
influenza surveillance in england and wales: october 1997 to june 1998.influenza caused low levels of mortality and morbidity in england and wales in the 1997/98 season. influenza viruses of the h3n2 and h1n1 subtypes were isolated in small numbers from community and hospital patients in november and december. their numbers subsequently increased to peak in february, h1n1 a week or two before h3n2. most of the h1n1 isolates were similar to the a/bayern/7/95-like virus, included in the vaccine recommended for 1997-98, whereas most h3n2 isolates were a/sydney/5/97-li ...19989854882
evaluation of recombinant a/victoria/3/75 (h3n2) influenza neuraminidase mutants as potential broad-spectrum subunit vaccines against influenza a.current influenza vaccines require repeated administration for long-term protection. failure to develop broad-spectrum vaccines may be attributed to the chronic presentation of hypervariable, immunodominant epitopes displayed on the viral surface that keep the immune response somewhat fixed and limited by suppression of broadly neutralizing, low-titered antibodies. to test this hypothesis, we have attempted to dampen the immunogenicity of variable epitopes and potential immunodominant domains of ...19989856088
effect of prednisone on response to influenza virus vaccine in asthmatic children.to evaluate the immunogenicity of the influenza virus vaccine in children receiving short-course (a burst) prednisone therapy for acute asthmatic exacerbations.19989856428
multiple genetic reassortment of avian and human influenza a viruses in european pigs, resulting in the emergence of an h1n2 virus of novel genotype.novel h1n2 influenza a viruses which were first detected in pigs in great britain in 1994 were examined antigenically and genetically to determine their origins and establish the potential mechanisms for genetic reassortment. the haemagglutinin (ha) of all swine h 1 n2 viruses examined was most closely related to, but clearly distinguishable both antigenically and genetically from, the ha of human h1n1 viruses which circulated in the human population during the early 1 980s. phylogenetic analysi ...19989880008
[impact of influenza epidemics and efficacy of vaccination among geriatric inpatients].to determine the impact of influenza epidemics among geriatric inpatients and to monitor the clinical efficacy of influenza vaccination, the influenza infection rate in non-vaccinated inpatients was determined serologically and the incidence of febrile episodes and death were compared between the vaccinees and non-vaccinees hospitalized in the referred hospital from january through september, 1995. three influenza subtypes, influenza a/h1n1, a/h3n2, and b, were endemic simultaneously from januar ...19989503786
low plasma levels of adrenocorticotropic hormone in patients with acute influenza.plasma levels of adrenocorticotropic hormone (acth) and cortisol were measured in young adults with influenza virus type a (h3n2) infection for whom cultures were positive and in comparable controls without symptoms or other evidence of illness. the mean plasma acth level +/- se in 19 patients with acute influenza was 13.5 +/- 2.1 pg/ml compared with 23 +/- 3.2 pg/ml in 11 controls (p = .02). mean plasma acth levels +/- se had risen to 21 +/- 4.1 pg/ml in specimens obtained from patients during ...19989524849
effective prophylaxis of influenza a virus pneumonia in mice by topical passive immunotherapy with polyvalent human immunoglobulins or f(ab')2 fragments.the effectiveness of polyvalent plasma-derived human immunoglobulins (ivig) in passive immunotherapy of influenza virus pneumonia was assessed, using the strain scotland (a/scotland/74 (h3n2)) adapted to balb/c mice by repeated lung passages. haemagglutinin antibodies in two batches of ivig at 10 mg/ml had a titre of 1/16. intravenous injection of 1000-5000 microg of ivig, 3 h after infection, gave 60-70% protection, whereas intranasal injection of 25-50 microg protected 90% of mice infected wit ...19989528903
thujaplicin-copper chelates inhibit replication of human influenza viruses.the effects of alpha-, beta- and gamma-thujaplicins and six of their metal chelates on human influenza virus-induced apoptosis in madin-darby canine kidney (mdck) cells were examined by dna fragmentation and flow cytometry. among the compounds tested, thujaplicin copper chelates inhibited apoptosis induced in the infected mdck cells with influenza a/pr/8/34(h1n1), a/shingapol/1/57(h2n2), a/aichi/2/68(h3n2) and b/lee/40 viruses, at concentrations of more than 5 microm. these results indicate that ...19989806486
use of recombinant nucleoproteins in enzyme-linked immunosorbent assays for detection of virus-specific immunoglobulin a (iga) and igg antibodies in influenza virus a- or b-infected patients.the nucleoprotein genes of influenza virus a/netherlands/018/94 (h3n2) and influenza virus b/harbin/7/94 were cloned into the bacterial expression vector pmalc to yield highly purified recombinant influenza virus a and b nucleoproteins. with these recombinant influenza nucleoproteins, enzyme-linked immunosorbent assays (elisas) were developed for the detection of influenza virus a- and b-specific immunoglobulin a (iga) and igg serum antibodies. serum samples were collected at consecutive time po ...19989817867
influenza a virus infection increases ige production and airway responsiveness in aerosolized antigen-exposed mice.respiratory viral infection is known clinically to promote sensitization to antigen inhalation and the development of asthma.19989819289
characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor gs 4071.an oral prodrug of gs 4071, a potent and selective inhibitor of influenza neuraminidases, is currently under clinical development for the treatment and prophylaxis of influenza virus infections in humans. to investigate the potential development of resistance during the clinical use of this compound, variants of the human influenza a/victoria/3/75 (h3n2) virus with reduced susceptibility to the neuraminidase inhibitor gs 4071 were selected in vitro by passaging the virus in mdck cells in the pre ...19989835519
responses to influenza vaccination in different t-cell subsets: a comparison of healthy young and older adults.t-lymphocyte responses to influenza vaccination were measured in healthy young and older adult volunteers. all participants were vaccinated with the 1995-96 trivalent influenza vaccine. cytokine and granzyme b levels were measured in peripheral blood mononuclear cells (pbmc) cultures after virus stimulation, prior to and 4 and 12 weeks after vaccination. the major findings in the older adult group were the different types of helper t-cell (th) responses to each of the vaccine strains of virus an ...19989778750
immunogenicity and efficacy of dna vaccines encoding influenza a proteins in aged mice.influenza is a leading cause of morbidity and mortality in older persons. the current influenza vaccine is only modestly successful, in part because of an age-related decline in immunogenicity and also because it induces only type-specified immunity. to overcome this, we evaluated dna vaccines encoding a/pr8/34 haemagglutinin (ha) and nucleoprotein (np) in young and aged balb/c mice. control mice were given formalin-inactivated a/pr8/34, control dna, or a non-lethal dose of pr8. aged mice given ...19989778751
evaluation of live, cold-adapted influenza a and b virus vaccines in elderly and high-risk subjects.we have evaluated the use of live cold-adapted influenza a and b virus vaccines in the elderly. cold-adapted influenza a and b virus vaccines are safe and modestly immunogenic in individuals over 65 years of age. however, our studies and those of other groups have shown that immune response to cold-adapted vaccines in this age group are modest. administration of combined cold-adapted influenza a and inactivated influenza vaccine has resulted in slightly higher frequencies of local and systemic h ...19989778752
[evaluation of a rapid enzyme immunoassay membrane test for diagnosis of influenza a virus infection].a rapid enzyme immunoassay membrane test, directigen flu a (becton dickinson, usa), was evaluated by using virus isolates and clinical specimens. the reference laboratory diagnosis was based on the results of virus isolation. directigen flu a was reactive for all subtypes of human influenza a viruses, including reference strains of h1n1, h2n2 and h3n2. moreover, h5n1 (hongkong/156/97) was also detected by this kit. no cross reactivity was detected with other respiratory viruses. directigen flu a ...19989780586
the plea against annual influenza vaccination? 'the hoskins' paradox' revisited.three papers by hoskins and collaborators published in the lancet in the 70s, have been challenging the common policy to annually vaccinate people at risk with inactivated influenza virus vaccine. from an analysis of a vaccination campaign in adolescent pupils of a boarding school and four influenza outbreaks in the period 1970-76, hoskins et al. concluded that annually repeated vaccinations would not confer protection against epidemic influenza in the long-term ('hoskins' paradox'). a review of ...19989796045
[impact of influenza a virus infection as a cause of pediatric hospitalization and use of rapid antigen test of influenza a virus].from the winter of 1997 to the spring of 1988, a severe epidemic caused by influenza a (h3n2) developed in japan. during the epidemic (december 1997 to february 1998), 239 children were admitted to the pediatric ward of nippon kokan hospital: as many as 76 (31.8%) were hospitalized with influenza a (h3n2) infection. most were young healthy children (mean age, 3.7 years), suggesting the need of influenza immunization for this age group. 110 specimens of hospitalized children were examined by rapi ...19989796186
influenza vaccine match with circulating strains and indicators of influenza strain impact - canada 1980 to 1992.to determine the similarity between influenza vaccine antigens and viruses associated with laboratory-confirmed infections by virus type/subtype, strain and influenza season; to correlate pneumonia and influenza hospitalization and mortality rates with the number of laboratory-confirmed influenza infections in an influenza season; and to develop predictive indicators of the likely incidence of current strains in the following season.199822346536
protection against a lethal avian influenza a virus in a mammalian system.the question of how best to protect the human population against a potential influenza pandemic has been raised by the recent outbreak caused by an avian h5n1 virus in hong kong. the likely strategy would be to vaccinate with a less virulent, laboratory-adapted h5n1 strain isolated previously from birds. little attention has been given, however, to dissecting the consequences of sequential exposure to serologically related influenza a viruses using contemporary immunology techniques. such experi ...19999882351
heterosubtypic immunity to lethal influenza a virus infection is associated with virus-specific cd8(+) cytotoxic t lymphocyte responses induced in mucosa-associated tissues.heterosubtypic immunity, defined as cross-reactive immune responses to influenza virus of a different serotype than the virus initially encountered, was investigated in association with virus-specific cytotoxic t lymphocyte (ctl) responses induced in systemic and mucosa-associated lymph nodes after immunization via different routes. mice immunized by the pulmonary route with live nonpathogenic influenza virus, strain udorn (h3n2), survived challenge with mouse-adapted pathogenic influenza virus, ...19999927573
role of neuraminidase in influenza virus-induced apoptosis.the virulent influenza virus clone 7a produced a greater level of apoptosis in mdck cells compared with the attenuated strain a/fiji. in both cases, apoptosis could be partially blocked by treatment with three anti-neuraminidase compounds [4-amino-(gr121158a) and 4-guanidino- (gg167; zanamivir) 2,3-dehydro-n-acetylneuraminic acid and 2,3-dehydro-2-deoxy-n-acetylneuraminic acid (dana)] when they were given to cells during the virus attachment/entry phase, but not subsequent to this phase. in cont ...19999934696
immunogenicity of influenza vaccine in patients with hemato-oncological disorders.the aim of this study was to measure the production of antihemagglutinin and antineuraminidase antibodies in patients with proliferative diseases of the hematopoietic or lymphatic system, immunized with influenza vaccine in the epidemic season 1995/96. twenty patients between 22 and 84 years volunteered for vaccination and were vaccinated subcutaneously with a single dose of split trivalent influenza vaccine ("fluarix", smithkline beecham) in autumn 1995 at the outpatients clinic, general hospit ...199910037036
evaluation of clinical case definitions of influenza: detailed investigation of patients during the 1995-1996 epidemic in france.using clinical predictors, we evaluated clinical case definitions of influenza during the 1995-1996 outbreak in france. thirty-five general practitioners collected virological specimens and clinical data. predictors of influenza virus infection were selected with logistic regression models. the results varied with the influenza virus subtype: temperature of >38.2 degrees c, stiffness or myalgia, rhinorrhea, and cough were predictive of influenza a/h3n2, whereas fatigue, lacrimation or conjunctiv ...199910064245
inhibition of viral adhesion and infection by sialic-acid-conjugated dendritic polymers.multiple sialic acid (sa) residues conjugated to a linear polyacrylamide backbone are more effective than monomeric sa at inhibiting influenza-induced agglutination of red blood cells. however, "polymeric inhibitors" based on polyacrylamide backbones are cytotoxic. dendritic polymers offer a nontoxic alternative to polyacrylamide and may provide a variety of potential synthetic inhibitors of influenza virus adhesion due to the wide range of available polymer structures. we evaluated several dend ...199910077477
protection of mice against a lethal influenza virus challenge after immunization with yeast-derived secreted influenza virus hemagglutinin.the a/victoria/3/75 (h3n2-subtype) hemagglutinin (ha) gene was engineered for expression in pichia pastoris as a soluble secreted molecule. the ha cdna lacking the c-terminal transmembrane anchor-coding sequence was fused to the saccharomyces cerevisiae alpha-mating factor secretion signal and placed under control of the methanol-inducible p. pastoris alcohol oxidase 1 (aox1) promoter. growth of transformants on methanol-containing medium resulted in the secretion of recombinant non-cleaved solu ...199910091596
influenza vaccination in liver transplant recipients.the immunogenicity of the trivalent inactivated influenza split virus vaccine (infusplit ssw 97/98) containing a/bayern/07/95 (h1n1)-like (a/johannesburg/82/96 [nib-39]), a/wuhan/359/95 (h3n2)-like (a/nanchang/933/95 [resvir-0]), and b/beijing/184/93-like (b/harbin/7/94) hemagglutinin antigens was tested in liver transplant recipients (txl-r).199910096534
a novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and il-2 or gm-csf. i. vaccine characterization and efficacy studies in mice.the aim of this study was to improve the potency of the currently used influenza subunit vaccines, which are of relatively low efficiency in high-risk groups. influenza a virus (shangdong/9/93) haemagglutinin/neuraminidase (h3n2), granulocyte-macrophage colony-stimulating factor (gm-csf) and interleukin-2 (il-2) were encapsulated, each separately or combined, in multilamellar vesicles composed of dimyristoyl phosphatidylcholine. balb/c mice were immunized once, i.p. or s.c., with 0.05-2.0 microg ...199910195636
antigenic drift in swine influenza h3 haemagglutinins with implications for vaccination policy.in order to explore the occurrence of antigenic drift in swine influenza a(h3n2) virus, we examined virus strains from outbreaks of respiratory disease among finishing pigs in the netherlands in 1996 and 1997 and from earlier outbreaks. in contrast to swine h3n2 strains from the 1980s, the recent isolates did not show significant cross-reactivity with human influenza a(h3n2) viruses from 1972-1975 in haemagglutination inhibition tests. these new strains form a separate branch in the phylogenetic ...199910195767
comparative analysis of evolutionary mechanisms of the hemagglutinin and three internal protein genes of influenza b virus: multiple cocirculating lineages and frequent reassortment of the np, m, and ns genes.phylogenetic profiles of the genes coding for the hemagglutinin (ha) protein, nucleoprotein (np), matrix (m) protein, and nonstructural (ns) proteins of influenza b viruses isolated from 1940 to 1998 were analyzed in a parallel manner in order to understand the evolutionary mechanisms of these viruses. unlike human influenza a (h3n2) viruses, the evolutionary pathways of all four genes of recent influenza b viruses revealed similar patterns of genetic divergence into two major lineages. although ...199910196339
dose dependence of ctl precursor frequency induced by a dna vaccine and correlation with protective immunity against influenza virus challenge.intramuscular injection of balb/c mice with a dna plasmid encoding nucleoprotein (np) from influenza virus a/pr/8/34 (h1n1) provides cross-strain protection against lethal challenge with influenza virus a/hk/68 (h3n2). ctl specific for the h-2kd-restricted epitope np147-155 are present in these mice and are thought to play a role in the protection. to assess the effectiveness of np dna immunization in comparison with influenza virus infection in the induction of ctl responses, we monitored the f ...199910201942
characterization of high-growth reassortant influenza a viruses generated in mdck cells cultured in serum-free medium.in the present study reassortant influenza a viruses of both the h1n1 and h3n2 type were generated in madin darby canine kidney cells grown in the absence of fetal bovine serum (mdck-sf1 cells). to this end, mdck-sf1 cells were simultaneously infected with one of the high-growth laboratory strains a/puerto rico/8/34 (h1n1) or a/hong kong/2/68 (h3n2) and recent h3n2 and h1n1 vaccine strains, respectively. reassortant viruses obtained from these mixed infections were genetically characterized by r ...199910217593
influenza vaccination in heart transplant recipients.seventy-nine heart transplant recipients were vaccinated with a trivalent influenza virus vaccine 1996/97 containing the strains a/singapore/6/86 (h1n1), a/wuhan/395/95 (h3n2), and b/beijing/184/93. the proportions of patients with protective levels of antibody (hi > or = 40) after vaccination ranged from 100% (a/singapore [h1n1]) to 31.6% (b/beijing) and their mean fold titer increases were lower than those recorded for vaccination of 109 healthy subjects with the same batch of vaccine. the vac ...199910328147
effects of egg-adaptation on the receptor-binding properties of human influenza a and b viruses.propagation of human influenza viruses in embryonated chicken eggs (ce) results in the selection of variants with amino acid substitutions near the receptor-binding site of the hemagglutinin (ha) molecule. to evaluate the mechanisms by which these substitutions enable human virus growth in ce, we studied the binding of 10 human influenza a (h1n1, h3n2) and b strains, isolated and propagated solely in mdck cells, and of their egg-adapted counterparts to preparations of cellular membranes, ganglio ...199910366560
[the feature of influenza virus activity and genetic characterization of ha1 gene of influenza a h3n2 viruses isolated from 1994-1997 in shenzhen].to understand the feature of influenza virus activity and genetic characterization of ha1 gene of influenza a h3n2 viruses isolated in recently years in shenzhen.199912569759
[influenza in 1997].the number of cases of influenza and influenza-like illness registered in poland in 1997 amounted to 1,578,494. this number of cases is 41.8% lower when compared with the previous year 1996. the incidence of influenza amounted to 4,084 per 100,000 inhabitants. the number of influenza cases registered in children aged up to 14 years was 557,033. this is 35.6% of total number of cases. the incidence of influenza in this group amounted to 6,828.7 per 100,000 and was 67% higher than total incidence. ...199910402849
paradoxical response to a novel influenza virus vaccine strain: the effect of prior immunization.repeated influenza immunization does not appear to adversely affect the serum antibody response to new influenza strains.199910403596
effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial.influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups.199910411194
risk indicators for the seroprevalence of mycoplasma hyopneumoniae, porcine influenza viruses and aujeszky's disease virus in slaughter pigs from fattening pig herds.epidemiological aspects of mycoplasma hyopneumoniae (mh), influenza h1n1 and h3n2 viruses, and aujeszky's disease virus (adv) were investigated in slaughter pigs from 50 fattening pig herds. herd factors as potential risk indicators for respiratory disease were obtained by means of a questionnaire. at slaughter, blood samples were collected from each herd, and the proportion of seropositive pigs per herd was assessed for each of these pathogens. the median herd-level seroprevalence of the agents ...199910416368
influenza virus subtype cross-reactivities of haemagglutination inhibiting and virus neutralising serum antibodies induced by infection or vaccination with an iscom-based vaccine.in order to study the levels of cross-reactivity of the influenza virus-specific antibody response upon infection or vaccination, usually hemagglutination inhibition assays are performed. in the present study post-infection ferret sera and serum samples obtained from cynomolgus macaques which were vaccinated with an iscom preparation based on the influenza virus strain a/netherlands/18/94 (h3n2) were analyzed for cross-reactivity in the hemagglutination inhibition assay and in virus neutralizati ...199910418897
human mannan-binding lectin inhibits the infection of influenza a virus without complement.mannan-binding lectin (mbl) is a c-type serum lectin that is believed to play an important role in innate immunity. it is one of the collectin family, which is characterized by having a collagen-like sequence and a carbohydrate recognition domain. mbl can bind to sugar determinants of several micro-organisms, neutralize them and inhibit infection by complement activation through the lectin pathway and opsonization by collectin receptors. bovine conglutinin and mouse mbl inhibit the infective and ...199910447758
antigenic drift of influenza a (h3n2) virus in a persistently infected immunocompromised host is similar to that occurring in the community. 199910476769
influenza a virus infection modulates the expression of type iv collagenase in epithelial cells.we investigated the effect of influenza a/beijing/353/89 (h3n2) virus infection on the expression of type iv collagenase in two different types of epithelial cell. depending on the cell line infected, the viral infection caused changes in the expression of type iv collagenase. the expression of matrix metalloproteinase-9 (mmp-9; 92 kda) but not of matrix metalloproteinase-2 (mmp-2; 72 kda) was stimulated in vero cells. in mdck cells, the mmp-2 production increased with the virus infection. accor ...199910481742
mutation of neuraminidase cysteine residues yields temperature-sensitive influenza viruses.the influenza virus neuraminidase (na) is a tetrameric, virus surface glycoprotein possessing receptor-destroying activity. this enzyme facilitates viral release and is a target of anti-influenza virus drugs. the na structure has been extensively studied, and the locations of disulfide bonds within the na monomers have been identified. because mutation of cysteine residues in other systems has resulted in temperature-sensitive (ts) proteins, we asked whether mutation of cysteine residues in the ...199910482558
genetic reassortment of avian, swine, and human influenza a viruses in american pigs.in late summer through early winter of 1998, there were several outbreaks of respiratory disease in the swine herds of north carolina, texas, minnesota, and iowa. four viral isolates from outbreaks in different states were analyzed genetically. genotyping and phylogenetic analyses demonstrated that the four swine viruses had emerged through two different pathways. the north carolina isolate is the product of genetic reassortment between h3n2 human and classic swine h1n1 influenza viruses, while ...199910482643
[a case of influenza a virus associated encephalopathy with bilateral thalamic hemorrhage].a three-year old girl was hospitalized in a semi-conscious state following a febrile convulsion. she did not recover despite treatment and died 16 days after admission. influenza a virus (h3n2) was detected from a throat swab from the patient, and serum hemagglutinin-inhibiting antibodies to the virus elevated from less than 8 to 256. brain ct revealed bilateral thalamic hemorrhage and peripheral low density. subarachnoid hemorrhage was also observed thereafter. based on clinical manifestations ...199910487024
selection of receptor-binding variants of human influenza a and b viruses in baby hamster kidney cells.cultivation of human influenza viruses in the allantoic cavity of embryonated chicken eggs leads to a selection of receptor-binding variants with amino acid substitutions on the globular head of the hemagglutinin (ha) molecule. such selection can be avoided by growing the human viruses in madin darby canine kidney (mdck) cells. in the present study, we tested whether baby hamster kidney (bhk) cells select receptor-binding mutants of human influenza viruses. after isolating h1n1, h3n2, and type b ...199910489338
influenza a virus outbreak in a neonatal intensive care unit.nosocomial infections with influenza virus are rarely recognized in neonatal intensive care units (nicu). an outbreak of influenza a virus infection in the nicu of an urban county hospital during the 1997 to 1998 influenza season is reported.199910493343
evaluation of immune responses to inactivated influenza vaccines prepared in embryonated chicken eggs and mdck cells in a mouse model.this study was initiated with the isolation of influenza a and b viruses from clinical throat swabs in both fertile chicken eggs (egg) and mdck cells, which were used in subsequent vaccine production in the above two hosts. on the basis of haemagglutination-inhibiting (hi) tests, immune mouse sera from mice vaccinated with mdck cell-derived vaccines revealed antigenic similarities among h3n2 or b viruses isolated in mdck cells or eggs. similarly, antiserum prepared by immunization with egg-deriv ...199910494959
generation and characterization of reassortant influenza a viruses propagated in serum-free cultured mdck-sf1 cells.the replacement of embryonated chicken eggs by tissue culture cells for the production of influenza vaccines is likely to take place in the near future. vaccines have already been produced in madin darby canine kidney (mdck) cells (brands et al, in this issue) and extensively tested in phase iii trials in humans (palache et al, in this issue) and it seems a matter of time before such vaccines will become available. for this reason, the generation of high-growth reassortants of influenza a virus ...199910494961
difficulties in standardizing the neuraminidase content of influenza vaccines.to achieve better standardization of influenza vaccines, an elisa immunocapture assay was developed for n2 neuraminidase quantification. this sensitive and highly specific assay was successfully applied to vaccine preparations produced in embryonated hens' eggs from 1992 to 1997 and to antigenically related viral suspensions produced in mdck cells. a study of the neuraminidase activity of prototype a/h3n2 strains stored at 4 degrees c showed the gradual development of enzymatic instability from ...199910494973
impact of the introduction of a/sydney/5/97 h3n2 influenza virus into south africa.in 1998 south africa experienced a major influenza epidemic that was characterized by extensive illness and an unusually early season. the impact of the epidemic was charted by measuring proxy indexes of influenza activity such as school absenteeism and excess mortality in persons older than 65 years. viruses isolated from patients of all age groups were analyzed both antigenically and at the molecular level to determine the characteristics of the influenza strain responsible for the outbreaks. ...199910534742
[influenza season 1998/99; composition of vaccine for 1999/2000].the first indication of influenza activity in the netherlands in the 1998/'99 season was the isolation of an influenza b virus in week 47 of 1998. in subsequent weeks influenza activity slowly increased, reaching a peak in week 6 of 1999. after a gradual decline for three weeks a second peak was reached in week 8 of 1999. the first wave of influenza activity was primarily caused by influenza b viruses, whereas during the second wave predominantly influenza a viruses of the a/h3n2 subtype were is ...199910535060
positive selection on the h3 hemagglutinin gene of human influenza virus a.the hemagglutinin (ha) gene of influenza viruses encodes the major surface antigen against which neutralizing antibodies are produced during infection or vaccination. we examined temporal variation in the ha1 domain of ha genes of human influenza a (h3n2) viruses in order to identify positively selected codons. positive selection is defined for our purposes as a significant excess of nonsilent over silent nucleotide substitutions. if past mutations at positively selected codons conferred a selec ...199910555276
[efficacy of influenza vaccine among geriatric inpatients: effect of previous vaccination and antibody induction by single and twice injections].to investigate the effect of previous influenza vaccination and the difference in antibody induction by single and twice injection of influenza vaccine in the elderly, hemagglutination inhibition (hi) antibody titers of the three types of influenza viruses were measured. influenza vaccination was done for 217 inpatients. for the patients who had influenza vaccination in the year prior to the study, influenza vaccine was administered once to 77 patients and twice to another 70 patients. influenza ...199910565120
h3n2 influenza a virus recovered from a neonatal pig in ontario--1997. 199910646069
[use of sentinel reporting clinics for influenza surveillance in the winter of 1996-1997].in a joint effort of the israel center for disease control, the national center for influenza in the central virology laboratory, together with a group of collaborating pediatricians and family physicians, a network for influenza surveillance was established in the winter of 1996-97. nose and throat swabs were obtained from 571 patients with flu-like illness. 133 (23%) were positive for influenza virus. both influenza a(h3n2) and b were isolated, predominantly influenza b during the beginning of ...199910914192
[diagnosis of an acute respiratory infection outbreak in children under 3 years of age in santiago de cuba].in november, 1996, there was an outbreak of acute respiratory infection in children under 3 in the province of santiago de cuba. 7 samples of nasopharyngeal exudates were received to determine the causal agent of the outbreak by indirect immunofluorescence technique (4 positive samples, 57.14%). they were inoculated in mdck cells culture and those cases that presented positive hemadsorption (6 isolates, 85.71%) were analyzed by indirect immunofluorescence techniques (6 positive samples, 100%) an ...199910887559
evaluation of trivalent, live, cold-adapted (caiv-t) and inactivated (tiv) influenza vaccines in prevention of virus infection and illness following challenge of adults with wild-type influenza a (h1n1), a (h3n2), and b viruses.trivalent, live, cold-adapted influenza vaccine (caiv-t) is highly effective in the prevention of influenza in children, and a variety of monovalent and bivalent cold-adapted influenza vaccines have been efficacious in adults. in order to determine the efficacy of caiv-t in healthy adults, we administered caiv-t, trivalent inactivated influenza vaccine (tiv) or placebo to 103 adults in randomized double-blind fashion, and then challenged those subjects who had pre-screening serum hemagglutinatio ...199910580204
influenza activity--united states, 1999-2000 season.influenza activity was low during october 3-november 6, 1999; influenza virus isolates were reported from 30 states, and four long-term-care facility outbreaks were reported from three states. the predominant viruses isolated were influenza type a(h3n2) viruses. this report summarizes influenza activity in the united states during october 3-november 6, 1999. it also summarizes u.s. influenza surveillance methodology, including the four primary sources of surveillance data, a modification to pneu ...199910599589
[evaluation of a rapid enzyme immunoassay for detection of influenza a virus among adult and elderly patients].directigen flu a, an enzyme immunoassay membrane test for the detection of influenza a virus, was compared with serum hemagglutinine inhibition assay in adult and elderly patients. throat specimens were collected by vigorous swabbing from febrile patients who were suspect for influenza by clinical symptoms and tested with directigen flu a. serum samples were collected from the patients at onset of illness and two to eleven weeks later and tested for antibody titer to influenza a/h1n1, a/h3n2, an ...199910624096
[the etiological structure of the morbidity from influenza and other ards on the territory of russia in the season of 1997-1998].the antigenic properties of 51 strains of influenza virus a(h1n1), isolated in different cities of russia during the epidemic of 1998, were studied. most of these strains (49) proved to be similar to virus a/bern/07/95 in the antigenic structure of hemagglutinin, but 2 strains isolated in ulan-ude were found to be closely related to new antigenic variants of this virus: a/beijing/262/95 and a/fukuoka/c7/98. the analysis of the antigenic structure of influenza-like diseases (ild) in different cit ...199910852031
effects of passage history and sampling bias on phylogenetic reconstruction of human influenza a evolution.in this paper we determine the extent to which host-mediated mutations and a known sampling bias affect evolutionary studies of human influenza a. previous phylogenetic reconstruction of influenza a (h3n2) evolution using the hemagglutinin gene revealed an excess of nonsilent substitutions assigned to the terminal branches of the tree. we investigate two hypotheses to explain this observation. the first hypothesis is that the excess reflects mutations that were either not present or were at low ...200010860959
herd factors associated with the seroprevalences of four major respiratory pathogens in slaughter pigs from farrow-to-finish pig herds.the objective of this study was to investigate sero-epidemiological aspects of mycoplasma hyopneumoniae (mh), influenza h1n1 and h3n2 viruses and aujeszky disease virus (adv) in fattening pigs from 150 randomly selected farrow-to-finish pig herds. different herd factors were examined as potential risk indicators for the percentage of pigs with antibodies against the 4 pathogens. the median within-herd seroprevalences of the pathogens were: mh 76%, h1n1 100%, h3n2 40% and adv 53%. there was a pos ...200010863948
expression of eotaxin by normal airway epithelial cells after influenza virus a infection.viral infection is known to cause lung inflammatory disease, including bronchial asthma. the mechanisms of inflammatory cell accumulation into the airways after viral infection are not well understood. eotaxin is a cc chemokine which is a potent and specific agonist for cc chemokine receptor 3 (ccr3). ccr3 is expressed on eosinophils, basophils and t lymphocytes. these cells are known to be key cells in the pathogenesis of asthma. although it has recently been demonstrated that airway epithelial ...200010867508
[variability of hemagglutinin from strains of influenza virus a (h3n2), isolated in russian from 1989 to 1999].analysis of 154 strains isolated in russia and cis countries in 1989-1999 showed that influenza virus a(h3n2) caused epidemics and epidemic rises 8 times, circulating together with a(h1n1) and b viruses. antigenic drift was revealed using polyclonal and monoclonal antibodies. analysis of antigenic properties of the viruses in the population showed that strains isolated during the same year were usually variants of one or rarely two reference strains. a drop of isolation rate of a(h3n2) strains o ...200010867992
cross-protection against a lethal influenza virus infection by dna vaccine to neuraminidase.cross-protection against a lethal influenza virus infection was examined in balb/c mice immunized with plasmid dnas encoding the neuraminidase (na) from different subtype a viruses. each na-dna was administered twice, 3 weeks apart, at the dose of 1 microg per mouse by particle-mediated dna transfer to the epidermis (gene gun) or at a dose of 30 microg per mouse by electroporation into the muscle. three weeks after the second vaccination, the mice were challenged with lethal doses of homologous ...200010869766
a simple restriction fragment length polymorphism-based strategy that can distinguish the internal genes of human h1n1, h3n2, and h5n1 influenza a viruses.a simple molecular technique for rapid genotyping was developed to monitor the internal gene composition of currently circulating influenza a viruses. sequence information from recent h1n1, h3n2, and h5n1 human virus isolates was used to identify conserved regions within each internal gene, and gene-specific pcr primers capable of amplifying all three virus subtypes were designed. subtyping was based on subtype-specific restriction fragment length polymorphism (rflp) patterns within the amplifie ...200010878047
hepatic decompensation in patients with cirrhosis during infection with influenza a.patients with chronic liver disease can develop hepatic decompensation during systemic infections. although gram-negative and gram-positive bacteria are well recognized as causes of decompensation, the effect of influenza virus infection on patients with chronic liver disease is poorly documented.200010632312
antigenic drift in the influenza a virus (h3n2) nucleoprotein and escape from recognition by cytotoxic t lymphocytes.viruses exploit different strategies to escape immune surveillance, including the introduction of mutations in cytotoxic t-lymphocyte (ctl) epitopes. the sequence of these epitopes is critical for their binding to major histocompatibility complex (mhc) class i molecules and recognition by specific ctls, both of which interactions may be lost by mutation. sequence analysis of the nucleoprotein gene of influenza a viruses (h3n2) isolated in the netherlands from 1989 to 1999 revealed two independen ...200010888619
systemic and mucosal isotype-specific antibody responses in pigs to experimental influenza virus infection.the immunoglobulin isotype-specific responses in serum and at the respiratory mucosa of pigs after a primary infection with influenza virus were studied. to do this, we developed an aerosol challenge model for influenza in specified pathogen-free (spf) pigs and isotype-specific enzyme-linked immunosorbent assays (elisas). ten-week-old pigs were inoculated without anesthesia in the nostrils with an aerosol of the field isolate influenza a/swine/neth/st. oedenrode/96 (h3n2). the infection caused a ...200010893003
influenza virus infection of desialylated cells.sialic acid has long been considered to be the sole receptor for influenza virus. the viral hemagglutinin (ha) is known to bind cell surface sialic acid, and sialic acids on viral glyco-proteins are cleaved by the viral neuraminidase (na) to promote efficient release of progeny virus particles. however, nws-mvi, a mutant virus completely lacking na, grows well in mdck cells continuously treated with exogenous neuraminidase (sialidase). exogenous sialidase quantitatively releases all sialic acids ...200010910970
influenza a virus infection complicated by fatal myocarditis.influenza virus typically causes a febrile respiratory illness, but it can present with a variety of other clinical manifestations. we report a fatal case of myocarditis associated with influenza a infection. a previously healthy 11-year-old girl had malaise and fever for approximately 1 week before a sudden, witnessed fatal collapse at home. autopsy revealed a pericardial effusion, a mixed lymphocytic and neutrophilic myocarditis, a mild lymphocytic interstitial pneumonia, focal bronchial/bronc ...200011111801
vaccine effectiveness for influenza in the elderly in welfare nursing homes during an influenza a (h3n2) epidemic.influenza vaccine effect on the occurrence and severity of influenza virus infection in a population residing in nursing homes for the elderly was studied as a cohort study during an influenza a (h3n2) epidemic in japan. of 22,462 individuals living in 301 welfare nursing homes, 10,739 voluntarily received inactivated, sub-unit trivalent influenza vaccine in a programme supported by the osaka prefectural government. there were statistically significantly fewer cases of influenza, hospital admiss ...200011117963
change in receptor-binding specificity of recent human influenza a viruses (h3n2): a single amino acid change in hemagglutinin altered its recognition of sialyloligosaccharides.human h3n2 influenza a viruses were known to preferentially bind to sialic acid (sa) in alpha2,6gal linkage on red blood cells (rbc). however, h3n2 viruses isolated in mdck cells after 1992 did not agglutinate chicken rbc (crbc). experiments with point-mutated hemagglutinin (ha) of a/aichi/51/92, one of these viruses, revealed that an amino acid change from glu to asp at position 190 (e190d) was responsible for the loss of ability to bind to crbc. a/aichi/51/92 did not agglutinate crbc treated w ...200011118381
influenza a virus infection and pulmonary microthromboembolism.this report presents the cases of two patients with rapidly progressive hypoxemia associated with influenza a(h3n2) virus infection, who were diagnosed with influenza related acute pulmonary microthromboembolism by serum d-dimer, lung perfusion and ventilation scans and computed-tomography scan of the chest, and were successfully treated by anti-coagulant therapy. the present cases suggest that acute onset pulmonary microthromboembolism should be considered in some patients with sudden, unexplai ...200011128871
[influenza virus surveillance in tama, tokyo--viral examinations in 1996/97, 1997/98, 1998/99, and 1999/2000 seasons].during the 1996/97, 1997/98, 1998/99, and 1999/2000 seasons, isolations of influenza virus and/or confirmations of hemagglutinin gene of virus from the throat swab of patients in 9 medical institutions in tama, tokyo were carried out by rt-pcr and tissue culture with mdck cells. in 1996/97 and 1997/98 seasons, type a (h3n2) was the predominant type of influenza virus, which was 85% in the 1996/97 and 97% in the 1997/98, but small-scale outbreaks with type b virus was also confirmed in the 1996/9 ...200011140082
epidemiological and virological influenza survey in dakar, senegal: 1996-1998.an influenza survey was conducted in seven sentinel sites in dakar, senegal from june 1996 to december 1998. throat or nasal swab cultures were randomly collected from 804 patients suffering from influenza-like symptoms. influenza viruses were isolated at a similar proportion in adults and in children (p = 0.29). strains of influenza b viruses were isolated from sporadic cases in 1997, whereas type a virus was associated with an isolated peak. proportions of influenza virus isolation varied from ...200011289677
[study on the origin of influenza a(h1n2) virus ha and na genes].to determine the origins of the ha and na genes of new subtype (h1n2) of influenza a virus.200011503022
[influenza and influenza-like acute respiratory diseases in slovakia in the 1999-2000 season].acute respiratory infections (ari) represent the most frequent cause of morbidity. their epidemic outbreaks become a severe problem not only in healthcare, but also in economical and social spheres.200011218957
[mechanism of the emergence of pandemic influenza virus strains and their control measures].the 1957 asian h2n2 and 1968 hong kong h3n2 pandemic strains of influenza are genetic reassortants between avian viruses and human strains. since avian viruses of any subtype can contribute genes in the generation of reassortants in pigs, none of the 15 ha and 9 na subtypes can be ruled out as potential candidates for future pandemics. the h5n1 influenza virus transmission from domestic poultry to humans in hong kong in 1997 further emphasized the need to have information on influenza viruses in ...200011225307
binding of influenza type a viruses to group b streptococcus and haemagglutination by virus-bound bacteria.we studied the bindings of human influenza a type viruses to group b streptococcus (gbs), types ia, ii, iii and iv, of sialic acid (sa)alpha2-3 linkage, using a/pr/8/34(h1n1) and a/memphis/1/71(h3n2). the viruses were found to bind to all types of gbs, with the exception of pr/8/34 for gbsii, and to elute from gbsia, iii and iv at 37 degrees c, except gbsii. electron microscopy confirmed these behaviours of the influenza viruses. the virus-binding capability of gbs types seemed to depend on the ...200011270858
a comprehensive systematic approach to identification of influenza a virus genotype using rt-pcr and rflp.amplification of influenza a virus gene segments by reverse transcription-polymerase chain reaction (rt-pcr) can be combined with enzymatic digestion to reveal unique restriction fragment length polymorphisms specific for h1n1 and h3n2 subtype viruses. we have used the method to provide a rapid, specific and reproducible identification of the genotype of high-growth influenza reassortants derived from a/puerto rico/8/34 (pr8). digestion of the gene segments amplified from wild-type viruses, pr8 ...200010921838
vitamin e supplementation increases t helper 1 cytokine production in old mice infected with influenza virus.compared with young mice, old mice infected with influenza virus have significantly higher pulmonary viral titres, although these can be reduced significantly with dietary vitamin e supplementation. t helper 1 (th1) cytokines, especially interferon-gamma (ifn-gamma), play an important role in defending against influenza infection. however, there is an age-associated loss of th1 cytokine production. prostaglandin e2 (pge2) production, which increases with age, can modulate the t helper cell funct ...200010929076
antiviral activity of nmso3 against respiratory syncytial virus infection in vitro and in vivo.nmso3, a sulfated sialyl lipid was evaluated for its efficacy against respiratory syncytial virus (rsv) and other myxovirus infections in cell culture. the median effective concentration (50% effective concentration, ec(50)) of nmso3 against replication of the long strain of rsv in hep-2 cells was 0.2 and 0.32 microm by optical elisa and the plaque reduction method, respectively. on the other hand, the corresponding values for ribavirin were 10.5 and 11.2 microm, respectively. nmso3 showed poten ...200010930645
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