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A Dessein

Publications and source records attributed to A Dessein.

At least 37 records · Page 2Linked to original sources
PubMed1991

Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni.

Severe clinical disease caused by the major human parasite Schistosoma mansoni is the consequence of high and prolonged infections. Epidemiological studies indicate that, for individuals having frequent contacts with cercaria-infested waters, both infection intensities and reinfection after treatment depend, in large part, on their intrinsic susceptibility/resistance to infection, suggesting the role of genetic factors in human resistance to S. mansoni. To investigate whether a major gene controls human susceptibility/resistance to infection by S. mansoni, segregation analysis of infection intensities, adjusted for the factors relevant in schistosomiasis (water contact, age, sex), was performed on 20 Brazilian pedigrees (269 individuals), using both the unified mixed model and the regressive model of analysis. The results are consistent with the hypothesis that there is a codominant major gene controlling human susceptibility/resistance to infection by S. mansoni. Parameter estimates indicate a frequency of .20-.25 for the deleterious allele; thus, about 5% of the population is predisposed to high infections, 60% is resistant, and 35% has an intermediate, although fairly good, level of resistance. These findings provide a genetic basis for earlier observations on the lower resistance and the predisposition to reinfection of certain individuals. In addition to the detection of a major gene effect, the data suggest that immunity to S. mansoni develops progressively during childhood to reach a maximum around the age of puberty. The implications of these results for the strategy to be used in endemic areas to reduce morbidity and to control parasite transmission are discussed.

Age Factors↗
PubMed1984

Eosinophil-mediated killing of schistosomula of Schistosoma mansoni: oxidative requirement for enhancement by eosinophil colony stimulating factor (CSF-alpha) and supernatants with eosinophil cytotoxicity enhancing activity (E-CEA).

Factors which enhance eosinophil-mediated killing of antibody-coated schistosomula of Schistosoma mansoni include semipurified eosinophil colony stimulating factor (CSF-alpha) and eosinophil cytotoxicity enhancing activity (E-CEA) present in supernatants from cultured mononuclear cells. We have examined the mechanism of enhancement. Both actions require oxygen in order to enhance killing and do not enhance killing under anaerobic conditions (P less than or equal to 0.005). E-CEA had no detectable effect upon oxidative metabolism. In contrast to CSF-alpha which, in our previous studies, increased superoxide anion productions and quantitative leukocyte iodination, E-CEA had no detectable effect upon oxidative metabolism. In order to test whether active oxygen products might mediate enhancement of killing, the effects of the addition of superoxide dismutase and catalase were tested. Neither enzyme showed inhibition of CSF-alpha or E-CEA enhancement of eosinophil-mediated killing. The effects of CSF-alpha and E-CEA were not additive. These studies suggest that both CSF-alpha and E-CEA exert enhancement of killing by means of an as yet unidentified oxygen requiring process.

Animals↗
PubMed1984

Suppressive effects of anti-mu serum on the development of collagen arthritis in rats.

Sprague-Dawley rats were maintained in environmentally isolated conditions and some of them were injected beginning at birth with rabbit anti-mu serum to suppress B-cell maturation. All rats were subsequently immunized with chick type II collagen. Ten (28%) of 36 rats injected with anti-mu antiserum failed to develop serum hemagglutinating antibodies to collagen, and there was a significant (P less than 0.0003) reduction in the IgG-specific antibody titer to collagen in these 10 rats compared to the other 26 rats in this group. Only 1 (10%) of the antibody-suppressed rats developed arthritis compared to 20 (77%) of the 26 other rats in the anti-mu-treated group (P less than 0.001). Twenty-two (61%) of 36 immunized rats administered rabbit anti-ovalbumin serum and 14 (88%) of 16 immunized rats kept in the axenic conditions developed arthritis. Delayed-type hypersensitivity to collagen did not differ significantly between the groups. These data provide indirect evidence that antibodies play a role in the inception of collagen arthritis.

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↗
PubMed1983

Eosinophil activation by colony-stimulating factor in man: metabolic effects and analysis by flow cytometry.

Substantial increases in the killing capacity of human eosinophils after in vitro incubation with human placental conditioned medium (HPCM), a standard source of colony-stimulating factor (CSF), have recently been described. In this article, the interaction between HPCM and purified human eosinophils is analyzed by flow cytometry and by effects on iodination, superoxide production, and protein synthesis. HPCM increased the intensity of natural eosinophil autofluorescence (aFlu) (460 nm) after the absorption of ultraviolet light (360 nm) in a manner that was both time and dose dependent. Measured in arbitrary units, eosinophil aFlu was 72 +/- 7.3 (arithmetic mean +/- SEM) and 121 +/- 3.2 after 18-hr incubations in the absence or presence of HPCM, respectively. The activity in HPCM responsible for these changes cochromatographed on Ultrogel AcA44 columns with CSF and with the less hydrophobic variant of CSF (CSF-alpha) on phenyl Sepharose. Mouse spleen, but not mouse lung, conditioned medium was also active on human eosinophils in this assay. Both CSF-alpha and mouse spleen conditioned medium also contain eosinophil colony-stimulating activity (CSA), whereas inactive CSFs with no effect on mature eosinophils, CSF-beta, and mouse lung conditioned medium also lack eosinophil CSA. CSF-alpha stimulated superoxide production of resting eosinophils (from 0.03 +/- 0.03 to 0.47 +/- 0.08 nmole cytochrome-c reduced/10(5) eosinophils) and of eosinophils incubated with preopsonized zymosan (from 0.15 +/- 0.06 to 0.73 +/- 0.07). It also stimulated iodination by resting eosinophils (from 0.76 +/- 0.16 to 2.60 +/- 0.72 nmoles l/10(7) eosinophils/hr) and of eosinophils incubated with preopsonized zymosan (from 7.52 +/- 2.08 to 29.8 +/- 1.32). In contrast, CSF-beta was inactive in these assays. CSF-alpha also stimulated, between 2- and 15-fold, the new protein synthesis of eosinophils. Thus, substances that stimulate the differentiation of progenitor cells into eosinophils also interact with peripheral mature eosinophils, and the activation of postmitotic cells may be a physiologic role of CSF-like molecules.

Cell Separation↗
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↗
PubMed1979

Interactions between human eosinophils and schistosomula of Schistosoma mansoni. II. The mechanism of irreversible eosinophil adherence.

Previous work (1)(1) has shown that normal human eosinophils show a preferential capacity, in comparison with neutrophils, to bind to antibody- coated schistosomula of Schistosoma mansoni. This effect is attributable to a temperature-dependent function of the eosinophil which renders its binding stable and irreversible by aggregated gamma globulin or Staphylococcus aureus protein A. In contrast, the binding of neutrophils is readily reversible by these agents. It has now been shown that the differences observed between eosinophils and neutrophils is a property of their interaction with living schistosomula. When dead or artificially damaged schistosomula were tested, neutrophils showed a markedly enhanced capacity to adhere, in both the presence and absence of anti-chistosomular serum. Subsequent experiments were designed to test the hypothesis that the strong, stable binding of eosinophils was attributable to degranulation, with release of granule contents which would then serve as ligands to bind the cell to the organism. First, an enhanced adherence both of eosinophils and of neutrophils could be demonstrated in the presence of eosinophil major basic protein (MBP) or of protamine, a high molecular weight cation. Second, the binding of eosinophils induced by concanavalin A (Con A) was found to differ markedly from that induced by antischistosomular serum. Con A-mediated binding of eosinophils was fully reversible by alpha-methyl-mannoside, was not associated with damage to the organism, and did not lead to degranulation of the cell, as estimated by measuring the release of MBP into the culture supernate. However, induction of degranulation of concanavalin A-bound eosinophils, but not of neutrophils, with the calcium ionophore A23187 converted the reaction into one which was no longer reversible by alpha- methylmannoside and in which damage to the organism now did occur. These findings support the hypothesis that the stable binding of eosinophils is associated with degranulation, a process which may contribute to the preferential capacity of this cell to mediate antibody-dependent damage to schistosomula.

Antibodies↗
PubMed1979

Characterization of the primary IgM response to GAT and GT: conditions required for the detection of IgM antibodies.

Primary IgM antibody responses to synthetic linear copolymers of L-glutamic acid, L-tyrosine, and L-alanine were investigated. The appearance of primary IgM anti-GAT antibodies was detected in BALB/c mice by using a solid phase radioimmunoassay (SPRIA) procedure. The finding was verified for GAT in responder mice and GAT-MBSA and GT-MBSA in nonresponder mice in an indirect plaque forming cell (PFC) assay by using a rabbit antiserum directed against the mulambda myeloma protein, MOPC 104E. Facilitated IgM PFC could be inhibited by a purified muK myeloma protein, TEPC 183. Maximal facilitated IgM plaque response was found to precede the IgG response by several days. A direct plaque assay was developed for the detection of IgM anti-GAT plaques using poly-L-lysine (PLL) to couple GAT to sheep erythrocytes (SRBC). GAT-SRBC coupled by the PLL method optimally couple 4 to 5 times less antigen to the indicator cell surface than does the CrCl3-coupling method routinely employed in our laboratory. These findings were extended to a conventional antigen, chicken gamma globulin (CgammaG). We found that a less dense epitope coat on the indicator cell surface favors detection of direct IgM PFC, whereas a more densely coated indicator cell favors the detection of facilitated IgM and IgG PFC responses.

Alanine↗
PubMed1978

Catabolite repression in Escherichia coli mutants lacking cyclic AMP.

The regulation of catabolite repression of beta-galactosidase has been studied in Escherichia coli mutants deleted for the adenyl cyclase gene (cya delta), and thus unable to synthesize cyclic AMP. It has been found that, provided a second mutation occurs either in the crp gene coding for the catabolite gene activator protein (CAP) or in the Lactose region, these mutants exhibit catabolite repression. If the catabolite repression seen in the mutant strains corresponds to the mechanism operating in wild-type cells the results would suggest that the intracellular concentration of cyclic AMP cannot be the unique regulator of catabolite repression.

Cyclic AMP↗
PubMed1978

Catabolite modulator factor: physiological properties and in vivo effects.

Catabolite modulator factor (CMF) specifically inhibits the expression of operons sensitive to catabolite repression. Systems known to be catabolite independent are not affected by CMF. The rate of metabolism of CMF depends on the extent of catabolite repression: it is slow under conditions of strong repression and high in catabolically derepressed cells. Cyclic AMP does not interfere with the rate of CMF metabolism. It has been found that a certain class of crp mutants are partially resistant to the repressive effect of CMF. Our results provide considerable support for the existence of an additional negative control in the regulation of catabolite repression.

Cyclic AMP↗
PubMedDate not supplied

Five-year impact of repeated praziquantel treatment on subclinical morbidity due to Schistosoma japonicum in China.

We report the 5-year impact (1996-2001) of repeated praziquantel chemotherapy on subclinical morbidity related to Schistosoma japonicum infection. We repeated stool examinations and hepatosplenic ultrasonography in a cohort of 120 individuals living on an island with endemic infection in Dongting Lake, China. Prevalence of schistosome infection fell by 43% and intensity (geometric mean eggs per gram) declined by 80% over the 5 years. However, transmission persisted at a dangerously high rate of 13% per year for re-infection or new infection in the cohort. The prevalence of left-lobe enlargement and dilated portal vein fell significantly (P < 0.01) to about half initial levels although a few patients progressed during the study period. At study endpoint, infection was nearly twice as common if the portal vein was dilated (23% versus 13%, respectively), but this association was not statistically significant (P > 0.05). However, endpoint infection was even more strongly associated with left-lobe enlargement (57% versus 15%, P < 0.01). The proportions of subjects with improved parenchymal and periportal fibrosis were much higher than the proportions of subjects that progressed (P < 0.05). Reduction of prevalence and intensity of infection, and improvement of subclinical morbidity, were benefits of repeated treatments. Further research is needed to understand why some patients developed fibrosis despite substantial reductions in egg counts and to evaluate the functional importance of residual subclinical morbidity after chemotherapy-based control in the lake and marshland area of China.

Adolescent↗