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Biomedical subjects

H P Taylor

Publications and source records attributed to H P Taylor.

13 recordsLinked to original sources
PubMed1997

Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift.

Ten antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10,000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody:other antibodies of > or = 2.0:1. The antiserum with the highest ratio (7.4:1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10,000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of > or = 1000 HIU/ml, and a low absolute titre of other antibodies (< or = 500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event.

Animals↗
PubMed1997

Development of new protocols and analysis procedures for the assessment of LBP by surface EMG techniques.

Spectral parameters of the surface electromyographic (EMG) signal from lumbar back muscles assessed during a fatiguing isometric contraction can be used to classify different categories of low back pain (LBP) subjects and control subjects without LBP. In the test protocol currently used at the NeuroMuscular Research Center at Boston University, subjects contract their back muscles at 80% of their maximal voluntary contraction (MVC) force. This fatigue-based protocol has been successfully applied to persons with subacute or chronic LBP; those in acute pain, however, have not been included because of their inability to perform a maximal exertion. In this paper we will examine the force sensitivity of the currently used EMG parameters and also give an overview of some of our efforts to develop new test procedures. Our goal is to develop force-insensitive surface EMG parameters that can be used for classification purposes in populations of subjects who develop low trunk extension forces. In addition, the development of a model to predict MVC from anthropometrical measurements will be presented.

Adult↗
PubMed1994

Competitive binding of neutralizing monoclonal and polyclonal IgG to the HA of influenza A virions in solution: only one IgG molecule is bound per HA trimer regardless of the specificity of the competitor.

Two-step solution competition assays were performed in solution with influenza type A virions and hemagglutinin (HA)-specific neutralizing monoclonal antibodies (mabs). These demonstrated that the binding of one molecule of IgG mab per HA trimer prevented the binding of mabs directed against other antigenic sites on the HA (site A, site B, or site D), even though these are topographically separate and antigenically independent. Furthermore the same procedures showed that one molecule of mab per trimer prevented the binding of polyclonal HA-specific IgG obtained from the serum of rabbits immunized with whole virus. This restricted binding is clearly a property of the intact virion, since others using purified HA have shown that up to four IgG molecules of different specificities can bind per trimer. Since the surface area of the globular head of the trimer is equivalent to approximately 10 nonoverlapping antibody footprints, it is not understood how one prebound IgG molecule prevents the binding of other IgG molecules.

Animals↗
PubMed1991

Cellular receptor for human cytomegalovirus.

The results of the studies reported strongly suggest that the binding of HCMV to a target cell in vitro is mediated by a glycoprotein membrane receptor having a molecular weight of approximately 30 kd. It has been further concluded that this particular molecule is the principal HCMV receptor, since it has been observed in each of the cell types that have been studied. As for the 28 and 60 kd molecules, the former may be a proteolytic degradation product and the latter a dimer of the 30 kd receptor. The precise contribution of the 92 kd that may allow for viral penetration into a host cell molecule to the initial recognition event is unknown at the present time.

Cells, Cultured↗
PubMed1990

The human cytomegalovirus receptor on fibroblasts is a 30-kilodalton membrane protein.

Previous studies have demonstrated that human cytomegalovirus (HCMV) binding to human foreskin fibroblasts (HFF) is mediated by a single type of molecule, likely a glycoprotein, which serves as a specific receptor for the virus. In the present experiments, HCMV was found to bind to an HFF membrane protein with an approximate molecular mass of 30 kilodaltons (kDa); weak binding to 28- and 92-kDa membrane components was also observed. Binding was specific, as it was inhibited by excess unlabeled HCMV. Radiolabeled HCMV also bound selectively to Raji and Daudi lymphoblastoid cell membrane proteins of the same molecular masses. The 30-kDa radiolabeled HFF membrane protein bound to HCMV in solution; this binding was also specific, as it was blocked by an excess of HCMV. These data suggest that a membrane protein with a molecular mass of approximately 30 kDa mediates HCMV binding to several cell types.

Cell Line↗
PubMed1989

Human cytomegalovirus binding to fibroblasts is receptor mediated.

The binding of radiolabeled human cytomegalovirus (HCMV) strain AD169 to human lymphocytes, lymphoblastoid cell lines, monocytes, and fibroblasts varied over a 20-fold range. Since maximum binding was observed with human foreskin fibroblasts (HFF), interactions of radiolabeled HCMV with this cell type were analyzed quantitatively. Binding of HCMV to HFF at 4 degrees C was specific and saturable; at low viral inputs specific binding averaged 16.4% of input and nonspecific binding was less than 1% of input. Binding curves yielded single-component linear Scatchard plots indicating an average Kd of 1.1 nM and 5,262 available virus-binding sites per cell. A two-component Scatchard curve was obtained at 37 degrees C and reflected viral internalization, since it could be converted to a single-component curve by the use of paraformaldehyde-fixed cells. HCMV strain Towne was found to bind to the receptor used by HCMV strain AD169 with similar affinity. HCMV failed to bind to protease-treated HFF or to HFF grown in the presence of inhibitors of glycosylation. Sialic acid residues, however, were not found to be important in binding. These data indicate that a single type of molecule, likely a glycoprotein, on the surface of HFF serves as a specific receptor for the virus.

Cells, Cultured↗
PubMed1987

Quantitative relationships between an influenza virus and neutralizing antibody.

In this quantitative study of the interaction of influenza virus with neutralizing antibody we have determined the maximum number of antibody molecules which can bind to the haemagglutinin (HA) of native influenza A/FPV/Rostock/34 (H7N1) particles in aqueous suspension and the minimum number which is required to cause neutralization. Using radiolabelled immunoglobulins approximately one IgG molecule, whether of monoclonal or polyclonal origin, binds per HA spike under conditions of antibody saturation. In the same manner, we have determined that when infectivity is neutralized by 63% (1/e) about 70 molecules of monoclonal IgGs HC2 and HC10 were bound per virus particle and this is supported by independent evidence from electron microscopy. However, the kinetics of neutralization were single-hit or at most, under critical conditions of low temperature (4 degrees) and minimal neutralizing concentrations of antibody, two-hit. This apparent conflict is reconciled by a hypothesis which proposes that neutralization occurs only when antibody binds to certain "neutralization relevant" HA spikes which are in the minority. It is suggested that these only differ from the majority of "neutralization irrelevant" HA spikes by their transmembrane interaction with the core of the virion.

Antibodies, Monoclonal↗
PubMed1985

Mechanism of neutralization of influenza virus by secretory IgA is different from that of monomeric IgA or IgG.

We have found that bile is a useful source of secretory IgA (scIgA) which can specifically neutralize influenza virus infectivity. Using purified scIgA, we compared the mechanism of neutralization with that mediated by IgA monomers (prepared from scIgA by differential reduction) and IgG. At 4 degrees C, scIgA prevented the attachment of neutralized virus, while neither monomeric IgA nor IgG had any affect on this process or on the subsequent stages of infection by which virion RNA accumulates in nuclei. At 25 and 37 degrees C, scIgA permitted the attachment of approximately half the neutralized virus, but the virus was not internalized. Clearly, the neutralization depends on the character of the antibody used. scIgA may act by steric hindrance (with attachment or penetration, depending on temperature), whereas IgA and IgG neutralize infectivity at a stage subsequent to accumulation of the virus genome in the nucleus.

Animals↗
PubMed1985

Mechanisms of neutralization of influenza virus by IgM.

IgM which neutralized influenza virus infectivity by over 99% prevented the attachment of only half the virus population to BHK cells at 37 degrees C. However, the half of the population that attached to cells was not internalized. Loss of infectivity brought about by IgM is thus totally different from that caused by neutralizing IgG which does not inhibit attachment or penetration.

Adhesiveness↗