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Biomedical subjects

F Brown

Publications and source records attributed to F Brown.

At least 361 records · Page 20Linked to original sources

Chemical basis of antigenic variation in foot-and-mouth disease virus.

One of the difficulties in controlling foot and mouth disease by vaccination is the occurrence of the virus as seven distinct serotypes because immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Moreover, the antigenic variation, even within a serotype, can be so great that immunity against the homologous strain of virus need not necessarily ensure protection against infection by other viruses within that serotype. Here we report the separation of three natural antigenic variants, distinguishable in cross-neutralization tests from an isolate of foot-and-mouth disease virus (FMDV). The serological differences could also be demonstrated by antisera elicited by synthetic peptides corresponding to residues 141-160 of the capsid polypeptide VP1, showing that this region contains a major immunogenic site of the virus. The results have practical implications for the choice of viruses for vaccine production.

Amino Acid Sequence↗

Early Homo erectus skeleton from west Lake Turkana, Kenya.

The most complete early hominid skeleton ever found was discovered at Nariokotome III, west Lake Turkana, Kenya, and excavated in situ in sediments dated close to 1.6 Myr. The specimen, KNM-WT 15000, is a male Homo erectus that died at 12 +/- 1 years of age, as judged by human standards, but was already 1.68 m tall. Although human-like in many respects, this specimen documents important anatomical differences between H. erectus and modern humans for the first time.

Animals↗

Recombinant vaccinia viruses as vaccines.

The prospect of live vaccines consisting of genetically modified vaccinia virus expressing foreign genes is exciting, but important issues concerning safety and efficacy need to be resolved.

Animals↗

Myristylation of picornavirus capsid protein VP4 and its structural significance.

We have obtained evidence that poliovirus and other picornavirus particles are specifically modified by having myristic acid covalently bound to a capsid protein. The electron density map of poliovirus confirms the position of the myristate molecule and defines its location in the virus particle. Analogies with other myristylated proteins suggest that the myristate moiety in picornaviruses may be involved in capsid assembly or in the entry of virus into cells.

Capsid↗

Non-responsiveness to a foot-and-mouth disease virus peptide overcome by addition of foreign helper T-cell determinants.

Study of the immune response to synthetic antigens has shown that uncoupled peptides can realize their potential as vaccines only if they contain domains that react with helper T-cell receptors and Ia antigens in addition to antibody binding sites. Here we consider whether genetically restricted non-responsiveness to an uncoupled peptide could be overcome by synthesizing a peptide with an additional helper T-cell epitope from a different protein. We demonstrate that H-2d mice, which are non-responders to the 141-160 VP1 peptide of foot-and-mouth disease virus (FMDV), can be converted into responders by immunization with peptides containing the FMDV sequence with defined 'foreign' helper T-cell determinants from ovalbumin or sperm whale myoglobin. Furthermore, the virus-neutralizing activity of the antibody raised against peptide was dependent on the determinant used. Thus, FMDV peptides with the added sequences 323-339 from ovalbumin and 132-148 from sperm-whale myoglobin elicited a high degree of neutralizing activity in B10.D2 mice. The sera from mice which received the peptide with the added sequence 105-121 from sperm whale myoglobin did not neutralize the virus, although they had high levels of anti-141-160 FMDV peptide activity. Our data indicate that the T-cell help given by the 'foreign' epitopes is B-cell clone specific. These results are likely to have important implications for the design of peptide vaccines.

Animals↗

Improved immunogenicity of a peptide epitope after fusion to hepatitis B core protein.

Synthetic vaccines for viral diseases can use defined regions of viral proteins as immunogens: the peptide sequence of amino acids 141-160 of the VP1 protein of foot and mouth disease virus (FMDV) elicits virus-neutralizing antibodies to protect guinea pigs, cattle and pigs either when coupled to a carrier protein or when administered in liposomes or in incomplete Freund's adjuvant. The immune response to these peptides is much lower than that to complete virus particles and the same sequence fused to the N terminus of beta-galactosidase did not produce a more potent immunogen than synthetic peptide alone. We report here an expression system for immunogenic epitopes linked to a carrier protein, hepatitis B core antigen, to form part of a virus-like complex which can present these epitopes to the immune system at high density. The immunogenicity of these structures approaches that of FMDV particles.

Animals↗

Epidural lipomatosis with lumbar radiculopathy: CT appearance.

Epidural lipomatosis is a relatively uncommon clinical entity in which large amounts of fat are deposited in the epidural space. In most of the previously reported cases of this entity an associated myelopathy has been reported. We describe a patient who presented with lumbar radiculopathy, which was probably caused by epidural lipomatosis.

Epidural Space↗

The cocaine threat.

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Breast Feeding↗

A major difference in the strategy of the calici- and picornaviruses and its significance in classification.

Pig kidney (1BRS-2) cells infected with vesicular exanthema virus (VEV), a calicivirus, did not contain any large precursor polypeptides similar to those found when they were infected with foot-and-mouth disease virus (FMDV). The largest induced protein found in the VEV-infected cells had a molecular weight identical with that of the virus structural polypeptide. This difference in strategy between VEV and FMDV, taken in conjunction with the morphological and structural differences described previously, provides strong evidence that the caliciviruses should not be included in the family Picornaviridae.

Animals↗