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A Aggarwal

Publications and source records attributed to A Aggarwal.

31 records · Page 2Linked to original sources

Antigenic variation of Giardia lamblia in vivo.

A single Giardia lamblia trophozoite can give rise in vitro to G. lamblia with varying surface antigens. To determine whether antigenic variation also occurs in vivo, gerbils were inoculated with defined G. lamblia clones and the surface antigens of the intestinal trophozoites were studied at different times during the infection. The proportion of monoclonal antibody 6E7-reacting trophozoites from WB C1-6E7S-inoculated gerbils had decreased significantly by day 3 postinoculation, indicating the presence of a heterogeneous population. On day 7, the 170-kilodalton antigen was no longer present and was replaced by a variety of antigens, including a major protein of 92 kilodaltons. With the exception of isolates from gerbils inoculated with WB A6-6E7S, the banding patterns of G. lamblia isolated from gerbils on day 7 or later were the same regardless of the clones used for inoculation. These studies show that G. lamblia changes its surface antigen(s) in vivo within 7 days following inoculation and appears to maintain the same set of surface antigens during the course of infection.

Animals

Giardia lamblia: RNA translation products.

The in vitro translation products of two different human isolates of Giardia lamblia, WB 2x and GS/E, were compared in order to determine common protein constituents and to identify proteins recognized by the infected host. Multiple polypeptides ranging from 20 to 185 kDa were synthesized using a rabbit reticulocyte cell-free translation system and although most were identical some differences were noted. GS/E compared to WB 2x showed different polypeptides of 23.5, 24.5, 26.5, 27.5, 32.5, 33.5, and 41 kDa. Some of these polypeptides were antigenic and were immunoprecipitated with anti-isolate antiserum from experimentally infected humans and gerbils. The sera of humans experimentally infected with isolate GS/M recognized a 24-kDa polypeptide from WB 2x and 23.5- and 24.5-kDa polypeptides from GS/E in vitro translation products. Sera from WB 2x- and GS/E-infected gerbils recognized 74- and 24-kDa polypeptides present in WB 2x translation products and 23.5-, 24.5-, 32.5-, 33.5-, and 74-kDa polypeptides when GS/E in vitro translation products were used. These studies identified both unique and common antigens in two different Giardia isolates and they may be of use in the serologic diagnosis of giardiasis and characterization of Giardia isolates.

Animals

Comparison of two antigenically distinct Giardia lamblia isolates in gerbils.

Previous studies established that some isolates of Giardia differ antigenically. In order to determine if antigenic differences resulted in altered biological behavior of host immune responses, two antigenically distinct isolates, WB and GS-E, were used to infect gerbils, and the course of infection, resistance to reinfection, and host humoral responses were measured. Maximum numbers of trophozoites were recovered on day 14 from the intestine of gerbils infected with both isolates, but by day 28, 75% of WB-infected gerbils were free of infection, while GS-E-infected animals continued to be infected until day 42. After curative metronidazole therapy, animals were challenged with the homologous or heterologous isolates. Gerbils previously infected with WB were resistant to challenge with WB and GS-E, while previously GS-E-infected gerbils were more resistant to challenge with the homologous isolate. Antibody responses were measured by ELISA to both surface and cytosol antigens and by IFA to the surface of Giardia. By IFA there was a greater reactivity using the homologous isolate, but with ELISA this was not as apparent. Complement independent cytotoxicity of sera was additionally tested against both isolates. Sera from WB-infected gerbils were cytotoxic to both WB and GS-E whereas sera from GS-E-infected gerbils were cytotoxic to GS-E only. These studies demonstrate that Giardia possessing different surface antigens have different patterns of infection and induce qualitatively and quantitatively different immune responses. Cytotoxicity of sera, most likely antibodies, correlated best with the development of resistance.

Animals

Lack of cellular cytotoxicity by human mononuclear cells to Giardia.

Cytotoxicity of mononuclear leukocytes (MNL) to Giardia lamblia was compared by using two techniques. The first method assessed the viability of surviving Giardia directly by culturing and the second method measured release of incorporated [3H] thymidine. Cytotoxicity, as measured directly by culturing and visual assessment, showed that the numbers of surviving Giardia decreased over time whether cultured with or without MNL but that Giardia survived significantly better in the presence of MNL at 18 hr (21.8 +/- 8.3% with MNL compared with 3.4 +/- 1.5% without MNL). Release of [3H]thymidine increased whether Giardia were cultured with or without MNL and although there was a tendency for increased release with MNL, there was no significant difference. Dead labeled Giardia released significantly more label in the presence of MNL than without MNL, suggesting that MNL cause release of [3H]thymidine after phagocytosis. The thymidine release assay therefore does not measure spontaneous cytotoxicity of MNL to Giardia.

Animals

Cytotoxicity of monoclonal antibodies to a subset of Giardia isolates.

Previous studies showed that some Giardia lamblia isolates differ and can be categorized on the basis of their DNA banding patterns after digestion with endonuclease restriction enzymes, surface antigens, and excretory-secretory (E-S) products. In the present study, monoclonal antibodies (McAb) were produced that reacted with one specific group of Giardia isolates. These McAb recognized a 170,000 dalton antigen, which was present on the surface of these Giardia and released into the medium as an E-S antigen. This antigen was previously characterized and found to distinguish this subgroup of Giardia. In addition, these McAb were cytotoxic only for this subgroup of Giardia. Immobilization occurred immediately, and killing was documented by 7 min. The mechanism(s) of killing remains unknown but was shown to be complement independent and did not occur with Fab'. These McAb identifies certain isolates and can be used to type Giardia.

Animals

Variability in the geometry of RNA double helices generated from dinucleoside building-blocks.

A graphical method is presented for the generation of helical parameters from single-crystal structures of RNA nucleic acid fragments that are minimally dinucleosides. The method is compared with other published procedures, for a number of text examples. The RNA double helices generated from three different salts of the dinucleoside monophosphate GpC are examined in relation to the variations in helix morphology that are produced. It is shown that small differences between these GpC salts can be amplified to very distinct helix characteristics.

Dinucleoside Phosphates

Resistance against Brugia malayi microfilariae induced by a monoclonal antibody which promotes killing by macrophages and recognizes surface antigen(s).

Several monoclonal antibodies were produced following the immunization of mice with infective larvae of Brugia malayi. One of these gives a positive fluorescence reaction on the surface of B. malayi microfilariae and this particular monoclonal antibody (IgM isotype) was able to mediate mouse peritoneal macrophage adherence to, and killing of, B. malayi microfilariae in vitro. Adherence and killing were enhanced by fresh normal mouse serum, suggesting a role for complement. When the same monoclonal antibody was passively transferred to mice harbouring microfilariae in their circulation, a complete clearance of microfilariae was observed in 70% of the animals. This monoclonal antibody was able to recognize antigenic determinants (of 110,000 MW) present on the surface of B. malayi microfilariae by radioimmunoprecipitation.

Animals