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J Modha

Publications and source records attributed to J Modha.

26 records · Page 2Linked to original sources
PubMed1990

Immune dependence of schistosomicidal chemotherapy: an ultrastructural study of Schistosoma mansoni adult worms exposed to praziquantel and immune serum in vivo.

This study examines the immune-dependence of praziquantel (PZQ) for the treatment of Schistosomiasis mansoni in mice. We have shown elsewhere from worm recovery data that the efficacy of PZQ is significantly enhanced when mice are treated concomitantly with antisera raised against antigens released from adult schistosomes, even though such antisera show no intrinsic helminthotoxic activity (Doenhoff et al. 1987, Doenhoff, Modha & Lambertucci 1988). Moreover, indirect immunofluorescence assays have shown that male worms exposed to the dual treatment regime in vivo bind antiserum to their dorsal surfaces in a pattern that seems to follow the outline of the dorsal tubercles. Scanning and transmission electron microscopy have now been used to further define the features of damage inflicted upon worms through exposure to antiserum alone, drug alone, or the two treatments in combination. Such investigations revealed that the antiserum induces a classical membrane repair process in worms of both sexes, but little other damage. PZQ causes the formation of spherical protuberances on the dorsal tubercles of male worms, while the dual treatment regime induces both kinds of damage in male schistosomes, but with much enhanced severity. The protuberances show evidence of explosion and some regions of the tegument become completely destroyed. Regions other than the dorsal surfaces of the male worms do not exhibit comparable trauma, and neither do the females. These data are discussed in relation to the known schistosomicidal activity of PZQ, the notion that male and female worms exhibit regional and sexual differences in susceptibility, documented evasive strategies of the parasite and the interdependence of immuno- and chemotherapy.

Animals↗
PubMed1988

Immunological identification of Schistosoma mansoni peptidases.

Precipitin arcs formed after immunoelectrophoresis of Schistosoma mansoni egg, worm and cercarial antigens with polyspecific rabbit antisera have been 'stained' at neutral pH with chromogenic enzyme substrates specific for proteases and peptidases. A total of 7 antigenically distinct enzymes with peptidolytic properties were identified. An enzyme which hydrolyzed phenylalanine naphthyl ester bonds was found in adult worm extracts, but appeared to be host-derived in so far as it was also immunoprecipitable from the same extracts by rabbit anti-normal mouse plasma. Three more phenylalanine naphthyl esterases were found, all stage-specific; one was in cercarial homogenates and two were in egg homogenates. A leucine naphthylamidase was also found in egg extracts, and it was antigenically distinct from, and did not react on dipeptide substrates that were hydrolyzed by two other leucine aminopeptidases present in extracts of all three stages of S. mansoni. The method provides a simple means of distinguishing constituents of complex mixtures of antigens by a combination of their immunological and biochemical properties.

Aminopeptidases↗
PubMed1988

An association between schistosomes and contrapsin, a mouse serine protease inhibitor (serpin).

An antigen in homogenates of adult Schistosoma mansoni worms grown in mice, and immunoprecipitated by polyspecific rabbit antiserum, has been identified as contrapsin, a mouse serine protease inhibitor (serpin). In the serum of some mice infected with S. mansoni contrapsin was found with altered immunoelectrophoretic characteristics when compared with contrapsin from uninfected mice.

Animals↗
PubMed1988

Anti-schistosome chemotherapy enhanced by antibodies specific for a parasite esterase.

The immune-dependent action of praziquantel has been investigated in Schistosoma mansoni-infected mice by passive transfer of rabbit antisera simultaneously with drug treatment. Significant synergistic activity was obtained with polyspecific sera against culture medium extracts of adult worms, but not with sera against detergent extracts or whole worm homogenates. Serum from a rabbit 'infected' with unattenuated S. mansoni cercariae was also synergistically active with praziquantel, and from this serum were derived two further active and monospecific sera which immunoprecipitated a 27,000 MW antigen with non-specific esterolytic enzyme activity. The antigen against which the monospecific sera reacted was detected by indirect immunofluorescence on the tubercles of drug-treated worms, but not on control worms. The immune-dependence of praziquantel thus appears related to drug-induced damage on the surface on the worm, which results in exposure of antigens sensitive to damage by antibody.

Animals↗
PubMed1986

Schistosoma mansoni egg antigens: preparation of rabbit antisera with monospecific immunoprecipitating activity, and their use in antigen characterization.

A simple method for producing monospecific rabbit antisera, applied originally to the constituents of human serum (Goudie et al. 1966), has been adapted for use with Schistosoma mansoni egg antigens. Replicate isolated immunoprecipitin arcs resulting from the immunoelectrophoretic reaction between an egg antigen and a polyspecific antiserum were excised, washed extensively to remove non-precipitated contaminants, homogenized, and emulsified with complete Freund's adjuvant. Rabbits were given weekly subcutaneous injections of the emulsion in multiple sites, and a monospecific precipitating antibody against the respective immunizing antigen generally resulted within 6 weeks of the commencement of immunization. Antisera raised in this manner against S. mansoni egg antigens omega 1, alpha 1 and kappa 5 have been used to characterize the antigen with respect to their stage- and species-specificity. After immunoabsorption to remove background activity, the sera could be used to detect unequivocally the respective antigens in crude egg homogenate that had been subjected to SDS-PAGE and electrotransfer to nitrocellulose paper.

Animals↗
PubMedDate not supplied

The association of steroids and schistosomicides in the treatment of experimental schistosomiasis.

The best therapeutic approach to acute schistosomiasis (Katayama fever) is still unsettled. In this paper we report a synergistic effect between schistosomicides and steroids in the treatment of the early stages of Schistosoma mansoni infection in the mouse. CBA mice infected with 150 S. mansoni cercariae were treated with oxamniquine or praziquantel and dexamethasone or prednisolone. The rate of parasite egg excretion by treated mice and appropriate controls was monitored, and the mice were perfused 43 d after infection for estimation of worm burdens and tissue egg densities. Mice treated with schistosomicides alone or with schistosomicides plus steroids had worm burdens of similar size. Significant reductions in egg counts were, however, recorded in faeces, and in the intestines and livers (with consequent reduction in liver pathology), of mice treated with schistosomicide and steroid, when compared to mice treated with schistosomicide alone or steroid alone. The apparent inhibition of fecundity of S. mansoni by combining these drugs has clear implications for treatment of the Katayama syndrome.

Animals↗