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Biomedical subjects

J R David

Publications and source records attributed to J R David.

At least 145 records · Page 8Linked to original sources
PubMed1982

Monoclonal antibodies recognizing determinants specific for the promastigote state of Leishmania mexicana.

Two monoclonal antibodies (IX-IF9-D8 and IX-5H9=C1) produced to a membrane enriched fraction of Leishmania mexicana amazonensis promastigotes have been demonstrated to be specific for the promastigote (insect) form and not the amastigote (mammalian host) form of the parasite. The antigens recognized by these monoclonal antibodies are not found on amastigotes isolated from infected animals or on amastigotes isolated from a macrophage cell line J774 infected initially with promastigotes. The antigens are not re-expressed by amastigotes cultured at 34 degrees C; however, amastigotes cultured at 24 degrees C that have begun transformation into promastigotes do express these antigens. The level of expression of these antigens in cultures of amastigotes undergoing transformation into promastigotes, increases with time from 16 to 36 h and appears to correlate with the percentage of promastigotes. Two protein molecules with apparent molecular weights of 40,000 and 92,000 have been identified by radioimmune precipitation as associated with L. mexicana promastigote stage specific determinants.

Animals↗
PubMed1982

Schistosomula of Schistosoma mansoni clear concanavalin A from their surface by sloughing.

The lectin concanavalin A (Con A) was used as a model probe to study the behavior of molecules bound to the surface of recently transformed schistosomula of Schistosoma mansoni. Con A binding was saturable (150-180 pg/organism) and specifically competed by alpha-methyl mannoside. Both FITC-Con A and 125-I-Con A were lost from the surface of schistosomula with a halftime of 8-10 h in culture in defined medium. A comparable decrease in the binding of Con A to schistosomula cultured and then labeled with the lectin indicated that the labeling procedure itself was not inducing the observed change. Internalization of Con A was not seen by either fluorescence microscopy or electron microscope radioautography. In addition, 70-80% of the radioactivity lost from the parasite was recoverable by TCA precipitation from the culture medium as intact Con A (27,000 mol wt on SDS PAGE). Thus, the mechanism of clearance of bound Con A from the surface of cultured schistosomula is apparently by sloughing of Con A molecules intact into the culture media and not by endocytosis and degradation. Con A binding sites, visualized with hemocyanin by scanning electron microscopy, appeared homogeneously distributed over the surface of schistosomula when organisms were labeled at 4 degree C or after fixation with glutaraldehyde. However, Con A and hemocyanin formed aggregates on the surface of schistosomula when labeling was performed at 37 degrees C, which suggests that lectin binding sites have lateral mobility within the plane of the membrane. These aggregates are likely independent of metabolism by the parasite because aggregation also occurs on the surface of organisms killed with azide.

Animals↗
PubMed1982

Expression of strain-specific surface antigens on Plasmodium falciparum-infected erythrocytes.

Antigenic determinants present on the surface of squirrel monkey erythrocytes infected with late developmental stages of P. falciparum were recognized through their ability to bind antibodies present in the serum of immune monkeys. Two different assays were used to demonstrate the presence of these antigenic determinants on the cell surface: the fluorescent labelling of intact cells in suspensions and the binding to protein A-Sepharose. Such determinants appear to be strain-specific and have, for a given strain, a variable expression according to whether the parasites are taken from intact or splenectomized animals or whether they have been grown in vitro.

Animals↗
PubMed1981

Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis.

Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered.

Aged↗
PubMed1981

IgE antibody and resistance to infection. I. Selective suppression of the IgE antibody response in rats diminishes the resistance and the eosinophil response to Trichinella spiralis infection.

Selective suppression of the total IgE antibody response has been achieved in rats by injection of rabbit anti-rat epsilon-chain antibodies. This IgE-specific suppression was maintained during the course of a natural infection by the nematode Trichinella spiralis. Depletion of the IgE antibody response resulted in a marked reduction of the number of eosinophils attracted to the T. spiralis larvae encysted in striated muscle. Blood eosinophilia following T. spiralis infection, although reaching normal peak levels, was abbreviated in IgE-suppressed animals. Moreover, IgE-depleted animals were more susceptible to the infection; they harbored two to three times more larvae encysted in their muscles than their control litter mates.

Animals↗
PubMed1981

Heat-labile and heat-stable anti-schistosomular antibodies in Kenyan schoolchildren infected with Schistosoma mansoni.

Two in vitro cytotoxicity assays using 51Cr-labelled Schistosoma mansoni schistosomula were performed on serum samples collected from 91 schoolchildren infected with S. mansoni from Machakos District, Kenya. One assay, which is believed to detect IgE/antigen complexes, uses unheated serum and human monocytes; the other, believed to detect IgG antibodies, uses heat-inactivated serum and unpurified peripheral blood leucocytes. Analysis of the data was complicated because the children were drawn from two separate studies and the data was extremely variable, probably because of the manner in which infections are acquired under natural conditions. There was a strong, positive regression of intensity of infection on age of the children, and evidence that IgG, but not IgE, activity was related to intensity of infection. There was no clear-cut relationship of IgE and IgG activities with the age of the children, and little evidence of any correlation between IgE and IgG activities within individual children. The implications of this latter dissociation and the possibility of either mechanism acting as the effector mechanism for concomitant immunity in man are discussed in the light of these results.

Adolescent↗
PubMed1981

Immune evasion by Schistosoma mansoni: loss of susceptibility to antibody or complement-dependent eosinophil attack by schistosomula cultured in medium free of macromolecules.

Schistosomula of Schistosoma mansoni, recovered either after penetration of cercariae through isolated rat skin or by mechanical transformation of cercariae, become fully resistant after 24-48 h of culture to damage by human blood eosinophils in the presence of human anti-schistosomular sera. Cultured schistosomula are also shown to lose their susceptibility to attack by human eosinophils in the presence of human complement. This resistance is related to the simultaneous reduction of the ability of human anti-schistosomular antibodies and human complement component C3 to bind to the surface of the cultured larvae. The development of insusceptibility to antibody, complement and eosinophil-mediated attack does not require the acquisition by the schistosomula of a protective coat of host or other macromolecules, since it is achieved in chemically defined culture medium free of serum and macromolecules. This supports the hypothesis that schistosomula undergo intrinsic changes which render them insusceptible to immune attack.

Animals↗
PubMed1981

Enzymatic treatment transforms trypomastigotes of Trypanosoma cruzi into activators of alternative complement pathway and potentiates their uptake by macrophages.

In the absence of bound antibody, trypomastigote bloodstream forms of Trypanosoma cruzi fail to activate the alternative complement pathway. We now demonstrate that treatment with trypsin and, to a lesser extent, with sialidase converts these protozoa into activators of the pathway, as judged by their lysis in normal sera or sera genetically deficient in fourth or second component of complement (C4 or C2) and their Mg2+-dependent consumption of C3 as measured by crossed immunoelectrophoresis. In addition, after pretreatment with enzyme and incubation in C5-deficient serum, trypomastigotes were shown to possess both C3 and properdin factor B (B) on their surface as judged by immunofluorescence. Requirement for the late components C5-C9 was suggested by the failure of C5-deficient sera to lyse trypsin-treated parasites. The inability to activate the alternative complement pathway was regained by these organisms after incubation in vitro. This restoration of insusceptibility was inhibited when puromycin was included in the culture medium. Treatment of the trypomastigotes with trypsin also potentiated their uptake by mouse peritoneal macrophages without apparent interference with their capacity to differentiate and multiply inside the cell. These findings suggest that untreated trypomastigotes normally escape recognition by the alternative pathway in vivo because of the presence on their surface of trypsin- and sialidase-sensitive regulatory molecules, the expression of which is dependent on protein synthesis.

Animals↗