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Biomedical subjects

J R David

Publications and source records attributed to J R David.

At least 127 records · Page 7Linked to original sources
PubMed1985

Identification by monoclonal antibody of a major (28 kDa) surface membrane antigen of Schistosoma mansoni.

Monoclonal antibody M.1 was generated from mice immunized with membrane enriched extracts of mechanically transformed schistosomula. M.1 bound to the surface membranes of cercariae and young (0-24 h post-transformation) schistosomula but did not bind to older schistosomula or cultured worms. M.1 immunoprecipitated an antigen of approximate molecular weight 27-28 kDa from schistosomula. Experiments using metabolic labeling showed that the antigen was actively synthesized by developing schistosomula. Further M.1 immunoprecipitated a similar 27-28 kDa antigen from membrane-enriched extracts of miracidia, lung and adult worms as well as from schistosomula.

Animals↗
PubMed1985

Enzymatic and quantitative variation in European and African populations of Drosophila simulans.

Allozyme polymorphism at 15 loci of D. simulans was studied in 7 natural populations from Europe, North and tropical Africa. Morphological traits were studied in nine European and eleven Afrotropical strains. Within a population, the biochemical polymorphisms of Drosophila simulans and its sibling Drosophila melanogaster are not very different, although D. simulans has a lower heterozygosity. Between-populations genetic differentiation is however much lower in D. simulans than in D. melanogaster. Several loci of D. simulans do exhibit latitudinal trends but these are relatively weak. For morphological traits, both species show an increase of size with latitude, but geographic variation is again less pronounced in D. simulans. Both species are native to tropical Africa and have colonised the rest of the world. During this process, D. simulans has undergone much less geographic differentiation than has D. melanogaster, so that the ecological success of the two species is not correlated with similarities in their genetic properties.

Africa↗
PubMed1985

Schistosoma mansoni: detection by monoclonal antibody of a 22,000-dalton surface membrane antigen which may be blocked by host molecules on lung stage parasites.

Monoclonal antibody M.2 binds to the surface membranes of cercariae and developing schistosomula. This antibody was generated from mice immunized with membrane-enriched extracts of mechanically transformed schistosomula. The antigen detected by M.2 was shown to persist on developing schistosomula for at least 96 hr post-transformation. M.2 also bound to the surface of living, cultured lung worms but not to freshly harvested lung worms. The ability of M.2 to bind to cultured lung worms coincided with the loss of host H-2 from the parasite surface. The apparent m.w. of the antigen was 22,000; an antigen with the same apparent m.w. was immunoprecipitated from cercariae, schistosomula, lung worms, and adult worms.

Animals↗
PubMed1984

Glycolipid-dependent interaction between human migration-inhibitory factor and mononuclear phagocytes.

It has been previously established in the guinea pig that the response of peritoneal macrophages to migration inhibitory factor (MIF) is enhanced by a macrophage glycolipid and that gangliosides reversibly bind MIF. This suggests that glycolipids function as cell surface receptors for MIF. In this report, it is demonstrated that the response of human peripheral blood monocytes to human MIF is augmented by preincubation of these cells with glycolipid-enriched material extracted from the human macrophage-like cell line U937 or human peripheral blood monocytes and with a purified glycolipid from guinea pig peritoneal macrophages. In addition, a mixed ganglioside preparation from bovine brain shows the same effect. In contrast, the pure gangliosides, GM1 and GD1a, and glycolipids from the HL-60 cell line, which is a MIF-unresponsive cell line, were not able to enhance the response to human MIF. The specificity of enhancement by particular glycolipids could not be attributed to an increased uptake of only enhancing glycolipids since there was no significant difference between the association of monocytes with radioactive liposomes containing biologically active or inactive glycolipids. Pronase treatment did not affect the enhancing activity of the U937 glycolipid-enriched material. Incubation of cells with glycolipids results in enhancement only if done at 37 degrees C and not at 4 degrees C. Therefore, the association of lipid with the monocyte surface appears to be dependent on temperature. Further evidence for the receptor nature of these enhancing glycolipids is provided by experiments involving affinity purification experiments. Coupling of bovine brain mixed gangliosides to agarose resulted in a matrix capable of reversibly binding MIF. GD1a-agarose was inactive in this respect.

Animals↗
PubMed1984

Dissociation of human interferon-gamma-like activity from migration-inhibition factor.

Supernatants harvested from concanavalin A-stimulated human peripheral mononuclear cells after 24 hr of incubation contain one interferon species similar to human interferon-gamma (IFN-gamma) with a pI of 4.6-5.3 (first day pH 5 IFN-gamm). In contrast, during the subsequent 24 hr of incubation two species with properties of IFN-gamma are produced with pI of 3.6-4.0 (second day pH 4 IFN-gamma) and 4.6-5.6 (second day pH 5 IFN-gamma), respectively. First day pH 5 IFN-gamma and second day pH 5 IFN-gamma have been found to differ on the basis of trypsin sensitivity. This pattern of polymorphism is similar to the pattern previously described for human migration-inhibitory factor (MIF) which can be separated into first day pH 5 MIF, second day pH 3 MIF, and second day pH 5 MIF. However, IFN-gamma-like species can be differentiated from MIF biochemically and antigenically. Fractions with second day pH 4 IFN-gamma have no MIF activity and fractions with second day pH 3 MIF contain no IFN activity. In addition, first and second day pH 5 MIF, which also contain IFN-gamma activity, can be separated from the latter by precipitation as well as neutralization with polyclonal and monoclonal anti-human MIF antibodies.

Antibodies↗
PubMed1984

Schistosoma mansoni. Anti-egg monoclonal antibodies protect against cercarial challenge in vivo.

Monoclonal antibodies that bind to surface membranes of developing schistosomula and/or cercarial tails were generated from mice immunized with living schistosome eggs or soluble egg antigen. These monoclonal antibodies detected at least three different surface epitopes. One surface antigen detected by anti-egg monoclonal antibody EG1C4B1 (E.1) persisted on the surface of developing schistosomula for 96 h posttransformation . The same or a cross-reactive antigen was also detected on the surfaces of S. japonicum and S. haematobium schistosomula and cercarial tails. Monoclonal antibody E.1 killed schistosomula in vitro as well or better than infected mouse sera and transferred immunity to naive mice when administered in vivo. The monoclonal antibody reduced the number of lung worms recoverable on day 4 postchallenge by up to 85% and reduced the adult worm burden up to 41% as compared with controls. The data also show that the molecular weights of the egg antigens detected by monoclonal antibody E.1 were different from those detected on schistosomula.

Animals↗
PubMed1984

Modulation of eosinophil cytotoxicity by blood mononuclear cells from healthy subjects and patients with chronic schistosomiasis mansoni.

Human blood mononuclear cells in culture release a factor(s) that markedly enhances eosinophil cytotoxicity. This factor(s) stimulates eosinophils to kill Schistosoma mansoni larvae at low antibody concentrations and cell/target ratios. A study of the mononuclear cells of 78 subjects with chronic schistosomiasis mansoni and 33 controls suggests that the production of eosinophil cytotoxicity enhancing activity (ECEA) is suppressed in most patients with S. mansoni infections. Suppression of ECEA production was not observed, however, with cells from many patients with heavy infections, including patients with hepatosplenomegaly. The possible role of ECEA in the development of pathology is discussed.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1984

Acetaldehyde utilization and toxicity in Drosophila adults lacking alcohol dehydrogenase or aldehyde oxidase.

Metabolic utilization and toxicity of acetaldehyde were studied in flies lacking alcohol dehydrogenase (ADH), aldehyde oxidase (AO), or both functions. Prior to the experiments, mutant alleles Adhn4 and mal were transferred to the same genetic background by 10 successive backcrosses. By comparison with wild-type flies, various deleterious, pleiotropic effects could be attributed to the mal allele but not to Adhn4. Of the four genotypes studied (mal, Adhn4, mal Adhn4, and wild), all were able to use acetaldehyde as a resource in a similar way. In spite of its high toxicity, acetaldehyde appeared a better resource than ethanol. Flies treated with intermediate acetaldehyde concentrations (around 0.5%) exhibited a very high interindividual heterogeneity which could reflect a physiological adaptation occurring as a consequence of the aldehyde treatment. Toxicity tests showed that ADH-negative flies were more sensitive to acetaldehyde than wild type, but this is most likely explained by the transformation of the aldehyde into alcohol. Our results show that the aldehyde metabolizing enzyme (AME) system in Drosophila is neither ADH nor AO. The existence of an aldehyde dehydrogenase is plausible.

Acetaldehyde↗
PubMed1984

Structure and arrangement of the beta-tubulin genes of Leishmania tropica.

We studied the organization and arrangement of the genes encoding beta-tubulin in the protozoan parasite Leishmania tropica and examined the structure and orientation of the beta-tubulin mRNA relative to the gene. There were found to be eight to nine beta-tubulin genes arranged in an array of direct tandem repeat units with a length of 3.8 kilobase pairs, and they were extremely homologous, if not identical, in sequence. These repeat units did not contain the alpha-tubulin genes. The transcribed sequences within the beta-tubulin genes were localized, and the orientation of the major alpha-tubulin mRNA was mapped on the gene by S1 nuclease analysis.

Animals↗
PubMed1983

Maturation in vivo of Schistosoma mansoni schistosomula after culture in vitro with granulocytes and antibody.

Seven experiments were carried out to test the relationship between the morphological assay for damage to schistosomula in vitro with toluidine blue and the loss of the ability of damaged organisms to mature in vivo. Schistosomula were prepared by penetration of rat skin and cultured for 12 to 38 h in the presence of various combinations of purified human eosinophils or neutrophils and heat-inactivated human antischistosomular serum. Samples were scored for microscopically detectable damage, and the remaining organisms were injected intravenously into normal mice. These mice were perfused after 5.5 to 7 weeks, and the recovery of adult worms was determined. After culture of schistosomula in medium alone, between 8.4 and 32.7% of injected organisms matured into adult worms. There was no significant difference in the capacity of freshly prepared and cultured schistosomula to mature in vivo. Schistosomula cultured with antibody alone showed no significant damage in vitro, and in only one of seven experiments was there a significant (35%) reduction compared with the medium controls in their capacity to mature in vivo. Schistosomula cultured with neutrophils alone or eosinophils alone showed no significant damage in vitro and no loss of viability in vivo. Schistosomula cultured with neutrophils and antibody showed a 28% reduction in recovery in one experiment but an increase in recovery (12 and 46%) in two other experiments. In contrast, schistosomula cultured with eosinophils and antibody showed evidence of both marked damage in vitro (22 to 93% dead organisms) and loss of viability in vivo (26 to 98% reduction in recovery) in all seven experiments. These findings justify the use of the toluidine blue morphological assay as an estimate of irreversible damage to schistosomula and confirm that human eosinophils and neutrophils differ markedly in their capacity to mediate antibody-dependent damage in vitro.

Animals↗
PubMed1982

Enhancement of human blood eosinophil cytotoxicity by semi-purified eosinophil colony-stimulating factor(s).

Purified human blood eosinophils, when incubated in human placental conditioned medium (a source of colony-stimulating factors) [CSF]) demonstrate an enhanced ability to damage antibody- or complement-coated schistosomula. This enhancement represents a 4- to 10-fold increase of eosinophil schistosomicidal ability and a 10-fold lowering of the threshold for antibody or complement required in the killing reaction. The activity that enhances eosinophil cytotoxicity and the eosinophil colony-stimulating activity in the placental conditioned medium are eluted in the same fraction (CSF-alpha) after chromatography on Sephadex G-100 and phenyl-Sepharose columns, suggesting that these two activities might be associated with the same molecule. CSF-alpha enhances the adherence step of the killing reaction: antibody-coated larvae were frequently found covered by several layers of eosinophils in tubes containing CSF-alpha. Such a degree of adherence was rarely seen in control tubes lacking CSF-alpha. This enhancement of the eosinophil adherence is detectable 45-60 min after addition of CSF-alpha to the culture. It is not affected by washing the cells after a short time of preincubation with CSF-alpha, and it occurs in the absence of protein synthesis, whereas colony-stimulating activity requires continuous protein synthesis and ceases when CSF is removed from the culture. Finally, CSF-alpha enhances the temperature-dependent reaction that insures the irreversibility of eosinophil attachment to schistosomula. These observations suggest that eosinopoietic factors could be responsible for some of the modified properties of blood eosinophils in eosinophilic individuals.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1982

Isolation of a guinea pig macrophage glycolipid with the properties of the putative migration inhibitory factor receptor.

We have previously established that preincubation of guinea pig macrophages with crude preparations of macrophage glycolipids enhances their response to a mediator of cellular immunity, migration inhibitory factor. This biologically active moiety found in the extracted material was attributed to a single glycolipid component. This component was purified to homogeneity by phase partition, ion exchange, adsorption, and thin layer chromatography. It migrates in the ganglioside region on thin layer plates, contains sialic acid and sphingosine. There is no apparent identity with any of the common gangliosides possessing the gangliotetraose structure. Homogeneity was demonstrated by rechromatography in four additional solvent systems. These results are discussed in the context of their implications for a deeper understanding of the putative receptor function of this glycolipid.

Animals↗
PubMed1982

Latitudinal variability of Drosophila melanogaster: allozyme frequencies divergence between European and Afrotropical populations.

Allelic frequencies at five polymorphic loci were determined in seven European and six Afrotropical populations of Drosophila melanogaster. African populations, which may be considered as ancestral for the species, showed a greater genetic diversity as measured by the number of alleles found. Within each geographic group (Europe or tropical Africa) genetic distances between local populations were very small (D = 0.027). By contrast, the average distance between European and African populations (D = 0.389) was more than 12 times bigger. It was previously known that various morphological or physiological differences, which probably reflect genetic adaptations to different environments, exist between these temperate and tropical populations. Data presented here suggest that the divergence in allozyme frequencies also reflects some selective mechanisms.

Africa↗