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Biomedical subjects

W U Tiu

Publications and source records attributed to W U Tiu.

35 records · Page 2Linked to original sources
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

Evidence of anti-embryonation immunity and egg destruction in mice sensitized with immature eggs of Schistosoma japonicum.

BALB/c mice sensitized by repeated injections of immature eggs of the trematode worm, Schistosoma japonicum, were challenged with low numbers of cercariae and evidence was sought for inhibition of embryonation by examination of eggs in livers and intestines at days 40 - 42 of infection. In contrast to the situation in unsensitized control mice, a greater proportion of dead eggs was noted in tissues of many of egg-sensitized mice. There was also a decrease in the proportion of mature eggs relative to control mice. A substantial number of egg - sensitized mice contained no eggs in the liver though eggs were readily detected in their intestinal walls. The data support the concept that immune effector mechanisms act on eggs in a manner that prevents their full development into a miracidium and thus a rich source of immunopathologic antigens.

Animals↗
PubMed1986

Resistance of 129/J mice to Schistosoma mansoni infection.

Mice of the strain 129/J bred at this Institute (WEHI 129/J) were exposed once or repeatedly to cercariae of Schistosoma mansoni and worm burdens determined. In keeping with reports of S. japonicum infection in these mice, a high level of resistance was recorded. Radio-labelled extracted antigens of S. mansoni adult worms were reacted with sera from exposed 129/J mice and infected BALB/c mice. Immunoprecipitated antigens preferentially recognized by antibodies in 129/J mice include proteins of Mr 99,000 and 21,000. Whether responses to these antigens are a cause or a consequence of resistance remains to be established.

Animals↗
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↗
PubMed1985

Antibody responses to the antigen Sj26 of Schistosoma japonicum worms that is recognized by genetically resistant 129/J mice.

Serum antibody responses of mice exposed to Philippine isolates of Schistosoma japonicum have been analysed by immunoprecipitation of exogenously radiolabelled antigens extracted from adult worms. Attention was focused on labelled protein antigens differentially recognized by sera of mice that differ genetically in their resistance status. Mice of the inbred strain 129/J can show high level resistance to first or repeated infection with S. japonicum. Even after six percutaneous administrations of 25 cercariae, approximately 50% of 129/J mice remain healthy with no or very few worms present in the portal system. Sera from 129/J mice exposed to S. japonicum consistently and differentially recognise an antigen of adult worms of mol. wt. 26,000. This antigen, termed Sj26, is not immunoprecipitated from S. mansoni adult worms by sera from resistant 129/J mice. Serum antibodies to Sj26 are present in at least some patients with a history of schistosomiasis japonica. Whether immune responses to Sj26 are involved directly in expression of resistance to S. japonicum remains to be determined. However, this antigen produced by cloned DNA in expression vectors, or isolated from adult worms, is an obvious candidate to be tested for vaccination efficacy in mice.

Animals↗
PubMed1985

Schistosoma japonicum: the modulation of lung granuloma and inhibition of egg maturation in mice by human sera.

Human sera taken from patients with chronic schistosomiasis japonica have been demonstrated to have two effects on mice. Sera from those patients reduced the size of granuloma in mice sensitised for accelerated granuloma formation to eggs entrapped in the lungs of mice injected with the sera shortly before and at day 2 after intravenous egg challenge. The sera with this effect on the mouse lung granuloma models caused large segmented precipitates in the optimised circumoval precipitin test (COPT). Such sera also reduced the rate at which eggs matured in the liver and intestines of mice infected with S. japonicum. The results strongly support our postulate that a major cause of granuloma modulation in cases of chronic schistosomiasis japonica is antiembryonation immunity and that mice provide useful models for the analysis of our postulate. Identification of egg antigens responsible for the anti-embryonation effect should facilitate progress towards the development of a vaccine against granulomatous disease.

Animals↗
PubMed1983

Sj23, the target antigen in Schistosoma japonicum adult worms of an immunodiagnostic hybridoma antibody.

An IgG2a mouse hybridoma-derived antibody (designated I.134) has been identified which binds to Schistosoma japonicum adult worms and which has immunodiagnostic potential (for detection of antibody) in schistosomiasis japonica in the Philippines. The target epitope of this hybridoma antibody is contained in a 23 000 molecular weight protein of adult worms as analysed by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis of immunoprecipitates and a gel overlay technique. This adult worm antigen has been labelled biosynthetically using 35S-methionine as well as exogenously using lactoperoxidase-catalysed radioiodination and the Bolton and Hunter reagent with intact worms. As anticipated, the low molecular weight protein antigen (designated Sj23) appears to be one of several major immunogenic proteins of worms which induce antibodies in infected Philippine patients.

Animals↗
PubMed1983

Hybridoma antibody-based competitive ELISA in Schistosoma japonicum infection.

A competitive enzyme-linked immunosorbent assay (ELISA) has been developed and compared with the circumoval precipitin test (COPT) for diagnosis of schistosomiasis japonica using Philippine sera. The assay is based on the inhibition, by sera, of the binding of a penicillinase-conjugated hybridoma-derived antibody, I. 134, to a crude Schistosoma japonicum adult worm extract. A change in pH subsequent to addition of the substrate is used as the indicator system. Development of the color change in this assay is relatively slow, a fact which presumably facilitates detection of inhibition by serum. Relative to the COPT, no false positive reactions were obtained and the false negative rate was less than 10%. A wide range of inhibitory titers was obtained using sera in the competitive ELISA similar to that found in a competitive radioimmunoassay using 125I-labeled I. 134. The competitive ELISA will be of more general application for diagnosis of schistosomiasis japonica than the competitive RIA using hybridoma antibodies, and will provide more precise quantitative information than is obtainable in the COPT.

Antibodies↗
PubMed1983

Resistance to reinfection with Schistosoma japonicum in the mouse.

BALB/c and outbred mice infected with a Philippine isolate of Schistosoma japonicum for 50 to 60 days expressed strong resistance to reinfection. The extent of this reinfection resistance ranged from 72 to 93% in 5 experiments (mean = 80% resistance) as determined by numbers of immature worms recovered from already infected and age- and sex-matched challenge control mice exposed 20 days previously to cercariae. Determination of numbers of recoverable worms from (the initial) infection suggest that adult worms are lost progressively during the period in which impressive resistance to reinfection is demonstrable. An important unresolved question is whether loss of adult worms is related in any way to expression of resistance to reinfection. Some indirect evidence indicates that the major component of reinfection resistance is expressed prior to day 4 of challenge infection. This evidence derives from analysis of lung petechiae which, in a primary infection, have been shown to provide an indication of number of adult worms which can be detected subsequently (e.g. at 30-40 days of infection). Although anti-parasite immune response have not yet been shown to be responsible for this apparent concomitant immunity, the magnitude of resistance to reinfection in the S. japonicum/mouse system should facilitate identification of any immunological effector mechanisms involved.

Animals↗
PubMed1982

Lung granulomatous hypersensitivity to eggs of Schistosoma japonicum in mice analysed by a radioisotopic assay and effects of hybridoma (idiotype) sensitization.

The radioisotopic assay for acute granulomatous hypersensitivity (AGH) to eggs of Schistosoma japonicum in mice sensitized with eggs in adjuvant has been examined in the high responder strain. C57BL/6. Responsiveness is expressed as the lung-kidney ratio of radioactivity in mice challenged intravenously with eggs and injected with 125I-iododeoxyuridine. Eggs vary in their AGH sensitizing and eliciting potency; eggs proven to be superior in the circumoval precipitation (COP) test for detection of human serum anti-S. japonicum antibodies are superior in the C57BL/6 AGH assay. CBA/H are non responders and BALB/c are low to intermediate responders and are thus different from C57BL/6 mice. Short-term infected CBA/H mice are low COP antibody responders relative to infected C57BL/6 and titres of IgM anti-egg antibodies are low in the CBA/H strain as determined in a solid-phase radioimmunoassay (RIA). Following egg sensitization, CBA/H mice are also lower responders than C57BL/6 mice in terms of antibodies with the specificity of a COP-positive IgM hybridoma-derived antibody, P.41, measured in a competitive RIA. No evidence has been obtained that alteration of the response to the target epitope of P.41 alters the responsiveness of C57BL/6 mice to S. japonicum eggs. Thus, large amounts of injected P.41 antibody do not alter lung AGH and induced anti-idiotype responses to the P.41 protein do not influence AGH in egg-sensitized C57BL/6 mice. However, immunization of C57BL/6 mice with another IgM anti-schistosome hybridoma antibody, 1.39, results in partial inhibition of lung AGH responsiveness. The nature of the effect of 1.39 immunization on AGH to eggs remains unknown, but further analysis of the phenomenon may lead to novel approaches to the control of granulomatous inflammatory disease in high responders.

Animals↗
PubMed1981

Attempts to standardize the circumoval precipitin test (copt) for Schistosomiasis japonica.

The circumoval precipition test (COPT) is a simple and inexpensive immunodiagnostic test for schistosomiasis japonica which, in the Philippines, has high sensitivity and specificity. Lack of standardization does, however, increase the variability of the test. Parameters which influence the COPT have been examined using large numbers of sera from known S. japonicum infected individuals. In this series of experiments, optimal conditions were determined to be as follows using 2 drops of neat serum and incubation at 37 degrees C in a sealed slide chamber; - approximately 100 eggs from 55 or 60 days infected rabbits for a 24 to 48 hour incubation period. COP reactions (i.e. precipitates associated with eggs) were much less obvious when either immature eggs or eggs obtained from long-term infected rabbits were used. The results emphasize the prime importance of the source of Schistosoma japonicum eggs in the performance of a standardized COPT.

Animals↗
PubMedDate not supplied

Schistosome circulating anodic antigen in serum of individuals infected with Schistosoma japonicum from the Philippines before and after chemotherapy with praziquantel.

The presence of the schistosome circulating anodic antigen (CAA) in serum of patients infected with Schistosoma japonicum from The Philippines has been investigated using an enzyme-linked immunosorbent assay (ELISA). Serum samples were tested from 48 patients who excreted S. japonicum eggs, 9 individuals with a negative stool examination, and 20 controls with both a negative stool and a negative circumoval precipitin test. No false positive result was detected for the unequivocally negative controls. CAA could be demonstrated in 72.9% of the egg-excreting patients. A positive correlation between parasite burden (eggs per gram of faeces) and antigen level (CAA titre) was found (Spearman's rho = 0.48, P < 0.001, n = 48). Four of 18 sera from the egg-negative individuals were positive in the ELISA. In view of the fact that anti-worm antibodies were also detected in these 4 sera, those reactions suggest active infection not detected by stool examination. In serum from patients treated with praziquantel, a significant drop in CAA titre was seen within 5 d after treatment (Wilcoxon's chi T = -2.23, P = 0.0258, n = 21). In conclusion, the detection of CAA by ELISA in S. japonicum infection can give valuable information in both individual diagnosis and therapeutic drug monitoring, as well as in epidemiological studies or disease control programmes.

Adolescent↗
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↗