Biomedical subjects
J Almond
Publications and source records attributed to J Almond.
A longitudinal study of tooth wear in orthodontically treated patients.
The primary objective of this study was to determine whether there is a relationship between incisal/occlusal tooth wear during the mixed dentition and subsequent wear of the adult dentition. Pretreatment orthodontic records taken during the mixed dentition (T1), as well as follow-up records taken an average of 20 years later (T2), were available for 223 orthodontically treated patients. Incisal/occlusal tooth wear was measured on a tooth-by-tooth basis from T1 and T2 stone casts with a four-category scoring system. Multiple regression analysis (R2 = 0.33) indicated that wear could be predicted at a given age during adulthood from wear observed on the deciduous mandibular canines and molars at T1 (p < 0.0001). This predictive relationship was modified by the age at which the T1 wear was observed (p = 0.029) and possibly by the sex of the patient (p = 0.10). These results indicate that adult tooth wear is not independent of the tooth wear that occurred as a child. Bruxism is suggested as a possible common etiologic mechanism that may account for the relationship between childhood and adult tooth wear.
The construction and characterization of poliovirus antigen chimeras presenting defined regions of the human T lymphocyte marker CD4.
Defined regions of the CDR2-like region of the T cell antigen CD4 that are implicated in the binding of the surface glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1) to CD4+ T lymphocytes have been engineered in place of antigenic site 1 of Sabin type 1 poliovirus. The antigenic properties of the recovered chimeric virus particles were investigated using monoclonal antibodies (MAbs) and polyclonal serum to CD4. None of the MAbs tested neutralized the chimeras, presumably because they are directed against conformational determinants of the V1 domain of CD4. In contrast, the three antigen chimeras were neutralized by polyclonal serum to CD4, which suggested that the CD4-derived sequences were presented in a relevant conformation. A panel of six MAbs were raised against one of the chimeras, and the epitopes were mapped by the selection of neutralization-resistant mutants and cross-neutralization studies. Five of the six MAbs reacted with soluble CD4 (sCD4) in ELISA, and one (MAb 1686) bound to CD4 expressed at the surface of HeLa cells. The high affinity interaction between gp120 and sCD4 was not blocked by MAb 1686, and the poliovirus-CD4 chimeras did not interact with gp120. These results demonstrate that poliovirus can be used as an epitope expression vector for the presentation of sequences in an immunodominant location on the virus particle which adopt a native or near-native conformation, and supports the findings of previous studies involving the presentation of epitopes derived from pathogens.
Recognition of poliovirus/HIV chimaeras by antisera from individuals with HIV infection.
The neutralization of five poliovirus/HIV chimaeras by serum from HIV-infected individuals was examined to evaluate the presentation of HIV envelope sequences, to assess the immune response of individuals to specific epitopes, and to relate it to the stage of disease. The sera were unable to differentiate between four of the chimaeras and the Sabin vaccine strain. With a fifth construct containing an immunodominant gp41 sequence, significant differential recognition was observed in approximately 67% of individuals with asymptomatic HIV infection [groups II and III of the Centers for Disease Control (CDC) classification of HIV infection] and 37% of patients with symptomatic disease (CDC group IV). Furthermore, among patients with CDC stage IV disease antibody levels against this construct and the titre achieved decreased with progression to further disease from approximately 40% in AIDS-related complex (ARC) patients (CDC group IVA and IVC-2 to 14% in those with AIDS (other group IV diseases). Loss of antibody to this construct did not result from a reduction in the anti-polio or anti-envelope response, but from a decline in antibody levels to the HIV sequence inserted in antigenic site 1.
Covariance of lowered capacity to induce interferon in human leukocytes and temperature sensitivity of type 3 poliovirus.
Attenuated poliovirus strains induce less interferon-alpha (IFN-alpha) in human leukocyte cultures than their parental wild-type strains or other neurovirulent strains. We have used a set of type 3 Leon/Sabin recombinant poliovirus strains to show that production of IFN in this system is closely associated with the genomic region that codes for capsid protein VP3; a mutation in this gene also causes the temperature sensitivity of the attenuated Sabin 3 strain and is partly responsible for the loss of neurovirulence of this vaccine strain. Sixteen independent poliovirus isolates, derived from the Sabin 3 virus but showing in vitro and in vivo markers of neurovirulence, were also tested. These gave IFN yields equivalent to or higher than those obtained with the neurovirulent Leon type 3 poliovirus. The relatively low IFN yields with the Sabin 3 virus seem not to be a direct consequence of its temperature sensitivity, but the two properties coincide with all the type 3 poliovirus strains tested.
Reversion of the attenuated and temperature-sensitive phenotypes of the Sabin type 3 strain of poliovirus in vaccinees.
Isolates of type 3 poliovirus from vaccine-recipients were characterized in terms of virulence, sensitivity of growth to high temperatures, and differences in genome structure from the Sabin type 3 vaccine strain. These included point mutations in the region of the genome coding for the structural proteins and in the 5' noncoding region, and the presence of type 1 or type 2 poliovirus genomic sequences resulting from intertypic recombination. Isolates from healthy vaccinees resembled those from vaccine-associated cases of poliomyelitis in all of these properties. Suppression of the temperature-sensitive phenotype was strictly correlated with reversion to virulence in nonrecombinant type 3 strains. Recombinant isolates were more attenuated than expected, even when they had lost all mutations known to attenuate the type 3 vaccine strain.
Nucleic acid sequence relationships between enterovirus serotypes.
Forty-eight different enterovirus serotypes were analysed by a nucleic-acid hybridization test using probes derived from the 3' end of coxsackievirus A21 (CA21) and B3 (CB3), poliovirus 3 (P3) and enterovirus 70 (E70). More than 90% of the serotypes could be detected with this collection of reagents. The CB3 probe reacted with all the coxsackie B viruses, with all three poliovirus serotypes, and with almost all of the 30 ECHO virus types tested. In addition some of the coxsackie A viruses and the BrDr 73 strain of enterovirus 71 gave a positive signal with this probe. The P3 probe detected all the poliovirus strains and also some coxsackievirus A isolates but no coxsackie B or ECHO viruses. A similar hybridization pattern as with the P3 probe was obtained when the CA 21 probe was used. The E70 probe appeared to be strain-specific. The results indicate that nucleic-acid hybridization is a useful method for rapid detection and subgrouping of enteroviruses during virus isolation, and that the test could be further developed for typing of the strains.
Application of monoclonal antibodies for the identification of the antigenic site for poliovirus neutralization.
Antigenic mutants of type 3 poliovirus were obtained by picking plaques formed in the presence of neutralizing monoclonal antibodies. All the mutants were clustered into a single operationally defined antigenic site based on their reactions with a panel of antibodies. Most of the mutations were shown to be located in the virion protein VP1 by SDS-PAGE and oligonucleotide mapping and fifteen of sixteen mutants had single point mutations in a region of VP1 encompassing only eight amino acids, suggesting that this is a major target for the neutralization of the virus. While other areas may also be required, it is likely that this region is a necessary component of a vaccine of any kind.
Measuring blood glucose levels.
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