Biomedical subjects

K M Davern

Publications and source records attributed to K M Davern.

24 records · Page 2Linked to original sources

PubMed1988

Molecular and serological characteristics of the glutathione S-transferases of Schistosoma japonicum and Schistosoma mansoni.

When aqueous extracts of Schistosoma japonicum and S. mansoni adult worms are passed over columns of glutathione-conjugated agarose, two molecular species of Mr 26,000 and Mr 28,000 are detected in eluates as analysed by SDS-PAGE, these eluates having glutathione S-transferase (GST) activity. The molecules, termed Sj26 and Sj28 from S. japonicum and Sm26 and Sm28 from S. mansoni, can be immunogenic in rabbits or mice and appear not to be linked together as subunits of GST heterodimers. The elution profile of SjGST (Sj26+Sj28) from glutathione columns resembles that of SmGST (Sm26+Sm28) and, by peptide mapping, radioiodinated Sj26 and Sm26 are related as are the two Mr 28,000 molecules. Similarities between radioiodinated Sj28 and Sm28 are also obvious on two-dimensional gel electrophoresis with some differences being observed between Sj26 and Sm26. The Mr 28,000 molecules are more prominent than the Mr 26,000 molecules and, although Sj28 and Sm28 is a poor immunogen in mice, immunological cross-reactivity between Sj28 and Sm28 is generally more readily detected than that between Sj26 and Sm26. Whether experimental vaccination against schistosomiasis japonica and schistosomiasis mansoni reported with cloned GSTs can be improved by incorporation of both Mr 28,000 and Mr 26,000 species into the vaccine remains to be determined. On this point, the present data suggest that vaccination of mice with Sj26 plus Sm28 should be a useful means of increasing antibody responses to the GSTs of S. japonicum.

Animals↗

PubMed1988

Schistosoma mansoni antigens differentially recognized by resistant WEHI 129/J mice.

Mice of the strain WEHI 129/J are genetically resistant to chronic Schistosoma mansoni infection. Resistance is expressed in at least 50% of mice, with the remaining mice showing normal susceptibility to infection. The serum antibody specificities in the resistant proportion of WEHI 129/J were analyzed at various times after exposure to cercariae by using both Western blotting and immunoprecipitation. Comparisons with the susceptible proportion of WEHI 129/J and other permissive mouse strains revealed four antigens that were differentially recognized by resistant mice at various times of infection: Sm25, an Mr 25,000 integral membrane protein of adult worms that was better recognized by resistant mice 40 to 50 days after exposure; Sm67, an Mr 67,000 water-soluble antigen of adult worms that was better recognized by resistant mice at days 30 to 40; Sm120, an Mr 120,000 antigen expressed by cercariae and adult worms that was differentially recognized, although inconsistently, at days 20 to 40 postexposure; and Sm26, an Mr 26,000 glutathione S-transferase that was uniquely recognized by resistant mice at day 20 in two of three experiments. Analysis of antibody specificities in (BALB/c x WEHI 129/J)F1 x WEHI 129/J backcross mice indicated that high responsiveness to Sm25 at days 40 to 50 correlated with resistance. The candidacy of these four molecules as vaccines for schistosomiasis mansoni is discussed.

Animals↗

PubMed1987

Responses in mice to Sj26, a glutathione S-transferase of Schistosoma japonicum worms.

The genetic variation in antibody responses of mice to glutathione S-transferase (GST) enzymes of Schistosoma japonicum worms, and in particular to a Mr 26,000 species termed Sj26, was analysed. Sera from infected mice, or mice immunized with adjuvant and an Sj26 beta-galactosidase fusion protein produced in Escherichia coli (Sj26FP), or purified near-native recombinant Sj26 produced in E. coli (rSj26), were assayed by enzyme-linked immunosorbent assay (ELISA) for antibody titres to GST purified from adult worms. Anti-GST antibody levels are high in a mouse strain, WEHI 129/J, that is genetically resistant to infection with S. japonicum. Antibody responses to GST are low in BALB/c mice and intermediate in most other mouse strains analysed such as CBA/H and C57B1/6. Responsiveness to Sj26 in adjuvant is dominant in (BALB/c x WEHI 129/J)F1 hybrids. BALB/c.H-2b and BALB/c.H-2k mice are higher responders than BALB/c. One feature of antibody responses to Sj26 is the variability within a group of mice. When rSj26 conjugated to the hapten azobenzenearsonate was used as immunogen, BALB/c mice produced substantial amounts of anti-Sj26 antibodies. In an attempt to correlate antibody levels with resistance in infected mice, a new functional assay was devised to measure the ability of sera to inhibit the binding of rSj26 to glutathione. However, there was no correlation between inhibitory titre in this assay and the numbers of worms recovered. In regard to the candidacy of GST as a vaccinating antigen in schistosomiasis japonica, the data raise the problem of variable responsiveness to the antigen that will need to be overcome by antigen modification and/or powerful adjuvants.

Animals↗

PubMed1987

Structure and function of candidate vaccine antigens in Plasmodium falciparum.

Analysis of Plasmodium falciparum antigens expressed in Escherichia coli has identified several different proteins as potential vaccine components. Fragments of one of these antigens, the ring-infected erythrocyte surface antigen (RESA) have been used to protect Aotus monkeys against overwhelming infection with P. falciparum. In this vaccine, trial protection correlated with antibody responses to two of three repetitive sequences in RESA. RESA is released from merozoites and becomes associated with the erythrocyte membrane at the time of merozoite invasion. The 3' repeat structure of RESA encodes a polyacidic sequence that has homology with the N-terminal sequence (cytoplasmic domain) of band 3, the erythrocyte anion transporter. These homologous sequences both include a recognition sequence for a protein tyrosine kinase. It is postulated that RESA disrupts the normal intermolecular interactions of the cytoplasmic domain of band 3 and that phosphorylation of RESA by an erythrocyte membrane kinase in some way regulates this function of RESA.

Amino Acid Sequence↗

PubMed1986

Mr 26,000 antigen of Schistosoma japonicum recognized by resistant WEHI 129/J mice is a parasite glutathione S-transferase.

Mice of the inbred strain 129/J bred at this Institute (WEHI 129/J) are relatively resistant to chronic infection with the parasitic helminth Schistosoma japonicum. In contrast to more permissive mouse strains such as BALB/c, the WEHI 129/J mice are high responders to a Mr 26,000 adult worm antigen designated Sj26. Cloned cDNAs corresponding to Sj26 have been identified in a S. japonicum phage lambda gt11 amp3 expression library, and their nucleotide sequences have been deduced. The predicted amino acid sequence of the antigen specified by these cDNAs shows striking homology with class mu isozymes of mammalian glutathione S-transferases (RX:glutathione R-transferase, EC 2.5.1.18). Extracts of adult worms contain glutathione S-transferase activity, and affinity chromatography of enzyme activity on glutathione columns leads to the purification of a Mr 26,000 molecule that comigrates with Sj26. Although vaccination studies in mice with a beta-galactosidase-Sj26 fusion protein from Escherichia coli are encouraging, more immunogenic preparations of the antigen are likely to be required to establish the utility of Sj26 as a model vaccine.

Amino Acid Sequence↗

PubMedDate not supplied

Anti-embryonation immunity in murine schistosomiasis japonica (Philippines).

The hypothesis that granuloma modulation and disease abatement in chronic infection with Schistosoma japonicum could be ascribed to antibody-mediated effects on egg maturation and egg viability, arose from studies performed with mice in the Philippines. This novel hypothesis has not yet been integrated into the schistosomiasis literature despite being formulated more than a decade ago. One reason for this is that the phenomenon might be confined to S. japonicum, even S. japonicum (Philippines).

Animals↗