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Biomedical subjects

R G Webster

Publications and source records attributed to R G Webster.

At least 325 records · Page 18Linked to original sources
PubMed1982

The prognosis for keratoplasty in keratoconus.

The long-term results in 326 eyes grafted for phakic keratoconus by the same surgeon were reviewed. All consecutive grafts performed for this disease with a minimum of five-year follow-up were included in the study. The mean follow-up was 11.3 years, with a range of 5 to 34 years. Ninety percent of grafts remained clear, 3% were nebulous but retained 20/40 vision, and 7% failed. Donor age was available for 188 of the 326 grafts. No relationship was found between donor age and long-term graft clarity even when older (more than 70 years) donor tissue was used. The visual acuity was measured with the patient's preferred optical device worn daily. Seventy-three percent of eyes achieved 20/40 or better vision after their initial graft.

Adolescent↗
PubMed1982

Virulence of avian influenza A viruses for squirrel monkeys.

Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus, A/Udorn/307/72 (H3N2). In squirrel monkeys, the 10 avian influenza A viruses exhibited a spectrum of replication and virulence. The levels of virus replication and clinical response were closely correlated. Two viruses, A/Mallard/NY/6874/78 (H3N2) and A/Pintail/Alb/121/79 (H7N8), resembled the human virus in their level and duration of replication and in their virulence. At the other end of the spectrum, five avian viruses were restricted by 100- to 10,000-fold in replication in the upper and lower respiratory tract and were clearly attenuated compared with the human influenza virus. In hamsters, the 10 viruses exhibited a spectrum of replication in the nasal turbinates, ranging from viruses that replicated as efficiently as the human virus to those that were 8,000- fold restricted. Since several avian viruses were closely related serologically to human influenza viruses, studies were done to confirm the avian nature of these isolates. Each of the avian viruses plaqued efficiently at 42 degrees C, a restrictive temperature for replication of human influenza A viruses. Avian strains that had replicated either very efficiently or very poorly in squirrel monkeys still grew to high titer in the intestinal tracts of ducks, a tropism characteristic of avian, but not mammalian, influenza viruses. These observations indicate that some avian influenza A viruses grow well and cause disease in a primate host, whereas other avian viruses are very restricted in this host. These findings also provide a basis for determining the gene or genes involved in the restriction of replication that is observed with the attenuated avian viruses. Application of such information may allow the preparation of reassortant viruses derived from a virulent human influenza virus and an attenuated avian virus for possible use in a live attenuated vaccine for prevention of influenza in humans.

Animals↗
PubMed1982

Failure to detect hemagglutination-inhibiting antibodies with intact avian influenza virions.

Avian influenza viruses replicate in a variety of mammals and birds, yet hemagglutination inhibition tests show that postinfection sera from these animals (e.g., ferrets and ducks) have insignificant levels of antibodies (Hinshaw et al., Infect. Immun. 34:354-361, 1981). This suggested that avian influenza viruses, in contrast to mammalian viruses, may not induce a significant humoral response. Studies reported here indicate that avian influenza viruses do induce high levels of antibodies in ferrets, ducks, and mice and produce long-lived memory for cytotoxic T-cells in mice. The failure to detect hemagglutination-inhibiting antibodies to avian viruses was explained by the finding that antibodies to avian influenza viruses were not detectable in hemagglutination inhibition tests with intact virus yet were readily demonstrable when hemagglutinin subunits were used. In addition, these sera contained high levels of neutralizing antibodies to the avian virus. These findings suggest that the hemagglutinins of avian and mammalian influenza viruses may differ in their accessibility to antibodies or the biological consequence of antibody attachment or both. The practical consequence of these studies is that hemagglutination inhibition tests with intact avian viruses fail to detect antibody and do not correlate with virus neutralization. The avian virus used in these studies, A/Mallard/NY/6870/78 (H2N2), replicated and caused mortality in BALB/c mice, emphasizing that the host range and virulence of avian viruses extends to mammals. The above findings suggest that avian viruses could infect mammals in nature, yet seroepidemiological studies with conventional hemagglutination inhibition tests could give misleading results.

Animals↗
PubMed1981

Immunogenicity of influenza A/USSR (H1N1) subunit vaccine in unprimed young adults.

Purified subunit vaccines (HANAflu) containing 20 microgram hemagglutinin of influenza A/USSR/90/77 (H1N1) alone or with 1-5% whole virus were compared to commercially available vaccines for reactogenicity and immunogenicity in unprimed young adults. Reactions to all vaccines were minimal. Sera from volunteers who received two intramuscular doses of vaccine or placebo were tested by hemagglutination-inhibition and neutralization tests. HANAflu with 1 microgram (5%) whole virus added was not different in immunogenicity from commercial vaccine. Both commercial vaccine and HANAflu with 1 microgram whole virus added gave higher seroconversion rates and more neutralization titers greater than or equal to 4 log2 than HANAflu alone and HANAflu + 0.2 microgram (1%) whole virus. Thus, the HANAflu subunit vaccine alone was less immunogenic than commercial vaccine in unprimed persons. However, addition of 1 microgram (5%) whole virus, but not 0.2 microgram (1%), eliminated this difference, There may be a role for addition of small amounts of whole virus to subunit influenza vaccines to overcome lower immunogenicity in unprimed populations.

Adolescent↗
PubMed1981

Specular microscopic and histologic observations in nonguttate corneal endothelial degeneration.

Six phakic patients with unilateral corneal edema and clinically normal-appearing fellow eyes were examined with specular microscopy and found to have endothelial pleomorphism and reduced cell counts in the nonedematous cornea. None of these patients had any previous eye disease, trauma, inflammation, or surgery. Clinically unrecognized endothelial disease was proposed as a cause for the unilateral corneal edema and was verified by light and electron microscopic studies in five patients. These pathologic findings vary somewhat from those found in Fuchs' dystrophy and may represent either a variant or a form of endothelial cell degeneration of as yet undetermined etiology. Our studies suggest that this condition is not detectable in the nonedematous cornea by standard high magnification biomicroscopy and requires the use of the clinical specular microscope to confirm the diagnosis in suspected cases.

Adult↗
PubMed1981

Composition and sequence studies show that A/duck/Ukraine/1/63 haemagglutinin (Hav7) belongs to the Hong Kong (H3) subtype.

The haemagglutinin chains HA1 and HA2 from the avian influenza virus A/duck/Ukraine/1/63 (Hav7, Neq2) have been subjected to amino acid analysis and N-terminal sequencing. Automated sequenator analysis of HA1 (40 cycles), after enzymic removal of the N-terminal pyroglutamic acid blocking group, and HA2 (43 cycles) showed that the Hav7 haemagglutinin closely resembled the human Hong Kong (H3) haemagglutinins including the presence of the characteristic extended 10 residue sequence at the N-terminus of HA1. These findings, together with the amino acid compositions for both chains, demonstrate that the Hav7 haemagglutinin is structurally similar to the Hong Kong (H3) haemagglutinins.

Amino Acid Sequence↗
PubMed1981

Analysis of antigenic drift in the haemagglutinin molecule of influenza B virus with monoclonal antibodies.

Antigenic drift in the haemagglutinin (HA) molecule of influenza B viruses was studied with monoclonal antibodies. Antigenic drift occurred in each of the 12 different epitopes studied and there was evidence that at least two antigenically distinguishable influenza B virus strains can co-circulate during an epidemic. The frequency of antigenic variation in the HA of influenza A strains. Haemagglutination inhibition (HI) tests on antigenic variants selected with 12 different monoclonal antibodies suggested that the antigenic determinants could be subdivided into three partially overlapping groups. Many of the antigenic variants selected with monoclonal antibodies were distinguishable from the parental virus with post-infection ferret sera, suggesting that the majority of the variants that do occur could have epidemiological potential.

Antibodies, Monoclonal↗
PubMed1981

Effect of test system on the ability of monoclonal antibodies to detect antigenic drift in influenza A(H1N1) virus haemagglutinins.

Results of analysing antigenic variation in the haemagglutinin (HA) molecule of naturally occurring influenza A (H1N1) viruses from 1977 to 1979 with monoclonal antibodies were found to be dependent in some instances on the test system used. In several instances A/USSR/90/77 HA-specific monoclonal antibodies had sharply reduced haemagglutination-inhibition (HI) titres with variant virus although they bound to the variant and A/USSR/90/77 HAs with similar efficiencies as judged by titration in a sensitive and accurate solid-phase immunofluorimetric assay. In another instance, the converse situation was observed: monoclonal antibodies having a reduced efficiency of binding to the HA of a variant virus nevertheless had comparable HI titres with the variant and with A/USSR/90/77. The chemical basis and epidemiological significance of these observations remain to be elucidated. Nevertheless, the finding that the reaction of monoclonal antibodies can, in some cases, be markedly dependent on the test system employed is of significance for the efficient design and correct interpretation of immunochemical studies which employ monoclonal antibodies to investigate the basis for variation in influenza strains.

Antibodies, Monoclonal↗
PubMed1981

Replication of avian influenza A viruses in mammals.

The recent appearance of an avian influenza A virus in seals suggests that viruses are transmitted from birds to mammals in nature. To examine this possibility, avian viruses of different antigenic subtypes were evaluated for their ability to replicate in three mammals-pigs, ferrets, and cats. In each of these mammals, avian strains replicated to high titers in the respiratory tract (10(5) to 10(7) 50% egg infective doses per ml of nasal wash), with peak titers at 2 to 4 days post-inoculation, similar to the pattern of human and other mammalian viruses in these animals. Most avian strains were recovered for 5 to 9 days post-inoculation. One avian H1N1 virus initially replicated poorly in pigs, but was adapted to this host and even transmitted to other pigs. Replication of the avian viruses occurred in the respiratory tracts of mammals, whereas, in birds, they replicate in the intestinal tract as well. The infected mammals had no significant disease signs and produced low levels of humoral antibodies; however, challenge experiments in ferrets indicated that they were immune. These studies suggest that influenza A viruses currently circulating in avian species represent a source of viruses capable of infecting mammals, thereby contributing to the influenza A antigenic pool from which new pandemic strains may originate.

Adaptation, Physiological↗
PubMed1981

Monoclonal antibodies to the influenza A virus nucleoprotein affecting RNA transcription.

Monoclonal antibodies were used to map the antigenic domains of the A/WSN/33 (HoN1) influenza virus nucleoprotein. Three nonoverlapping antigenic regions of the nucleoprotein were identified by using competitive-binding enzyme-linked immunosorbent assays. Monoclonal antibodies to two nucleoprotein domains inhibited in vitro transcription of viral RNA, suggesting that these specific regions of the nucleoprotein are topographically or functionally involved in RNA transcription.

Antibodies, Monoclonal↗
PubMed1981

The human cytotoxic T cell response to influenza A vaccination.

The human cytotoxic T lymphocyte (CTL) response to challenge with influenza A vaccine was studied. Six of eight volunteers given killed whole influenza virus A/USSR (H1N1) vaccine showed substantial increases on the level of CTL memory 1 month after immunization. The CTL measured at this time showed complete cross-reactivity in their specificity for influenza A/USSR (H1N1) and A/X31 (H3N2) infected cells and also showed HLA restriction. The level of CTL memory increased in only three out of nine donors given subunit vaccine and showed no change in those not given vaccine. If cytotoxic T cells are important in influenza prophylaxis, killed whole virus vaccine should offer better protection than subunit vaccine.

Antibody Formation↗