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A A Mahmoud

Publications and source records attributed to A A Mahmoud.

At least 91 records · Page 5Linked to original sources
PubMed1982

Isolation of Schistosoma japonicum egg glycoprotein antigens which sensitize mice to lung granuloma formation and elicit an immediate hypersensitivity response.

Crude Schistosoma japonicum soluble egg antigen (SEA) could be resolved into at least 25-30 Coomassie blue-reactive polypeptides when subjected to polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Two of these polypeptides also gave a strong reaction for carbohydrate with the periodic acid-Schiff (PAS) reagent. Although only four antigens could be demonstrated by double immunodiffusion in agar against the sera of mice with a 9-week S. japonicum infection, double antibody precipitation of 125I-labeled SEA, followed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, revealed the presence of at least 20-22 antigenic species. Crude SEA was fractionated by Concanavalin A-Sepharose 4B chromatography. The resulting fractions, together with crude SEA, were tested for their ability to subcutaneously sensitize mice to lung granuloma formation around S. japonicum eggs subsequently injected intravenously. Strikingly, only the egg glycoprotein antigen fraction, which bound to the lectin column and was eluted with alpha-methyl-D-mannoside, possessed demonstrable sensitizing activity. Likewise, only this glycoprotein fraction elicited a significant immediate (15-min) footpad response, when injected into the footpads of S. japonicum-infected mice. The biologically active glycoproteins were further purified by repetitive gel filtration chromatography. Two of the isolated glycoproteins (designated gp-1 and gp-2) were shown to be greater than or equal to 90% pure and to be PAS-reactive; whereas the third (gp-3) was found to be still heterogenous. When the individual purified glycoproteins were tested in the lung granuloma model, all three displayed significant sensitizing activity; however, gp-2 appeared to be the most active. Similarly, the same glycoprotein antigen elicited a significantly greater immediate footpad reaction in infected mice than did the others.

Animals↗
PubMed1982

Characterization of a purified glycoprotein from Schistosoma mansoni eggs: specificity, stability, and the involvement of carbohydrate and peptide moieties in its serologic activity.

A major egg glycoprotein (MEG) was purified from a crude soluble extract of Schistosoma mansoni ova (Egyptian strain) by successive steps of lectin affinity and ion-exchange chromatography. Radioiodinated MEG exhibited a single precipitation band upon immunodiffusion against antiserum from chronically infected mice, and ran as a single band on PAGE (Rf 0.38) and SDS-PAGE (Rf 0.36). Its estimated m.w. was 70,000. The degree of stage and species specificity of MEG and the effect of various treatments on its serologic reactivity were determined by radioimmunoassay (RIA). A low degree of cross-reactivity between MEG and similarly prepared soluble antigens from adult worms and cercariae was demonstrated by RIA inhibition tests, whereas a high degree of cross-reactivity was found between MEG and a crude soluble S. haematobium egg antigen. In similar RIA inhibition tests, the Puerto Rican S. mansoni had a lower degree of cross-reactivity with S. haematobium than the Egyptian strain. MEG was four times more abundant in SEA from a Puerto Rican strain of S. mansoni than in SEA from the Egyptian strain. The serologic reactivity of MEG was stable to heat at 100 degrees C for 60 min, to 0.1 N NaOH or HCl, and to 10% TCA. Treatment of MEG with pronase caused a limited fragmentation of the molecule and some loss of its serologic reactivity. Periodate oxidation resulted in a substantial loss of molecular mass and of serologic reactivity, leaving a low residual activity that is only partially cross-reactive with the bulk of MEG. These results suggest the importance of both carbohydrate and peptide moieties of MEG for its serologic reactivity.

Animals↗
PubMed1982

Adoptive transfer of modulation of granuloma formation and hepatosplenic disease in murine schistosomiasis japonica by serum from chronically infected animals.

The course of disease due to Schistosoma japonicum in C57BL/6J mice was examined. Animals infected with 25 cercariae of the Philippine strain of S. japonicum for 9 wk develop a peak portal hypertension of 13 +/- 0.6 cm H2O and mean hepatic granuloma area of 459 X 10(3) micrometers 2. By 30 wk, disease manifestations were reduced; mean portal pressure was 7 +/- 0.5 cm H2O and mean hepatic granuloma area was 12 X 10(3) micrometers 2. Adoptive transfer of serum but not 1 X 10(8) spleen or 4 X 10(7) lymph node cells from chronically infected mice resulted in lowering portal pressure and decreasing granuloma size in recipients. Granuloma formation in the sensitized lung model was also suppressed by serum from chronically infected mice. The immunosuppressive component of this serum was localized in the IgG1 fraction.

Acute Disease↗
PubMed1982

Analysis and preliminary purification of glycoproteins isolated from eggs in the urine of patients with Schistosoma haematobium infection.

Preliminary analysis and purification of glycoproteins from Schistosoma haematobium eggs were carried out with a small quantity of antigenic material obtained from the urine of infected human patients. A soluble egg extract was 125I-labeled and was fractionated by lectin affinity chromatography for separating egg glycoproteins. The crude glycoprotein fraction was run on SDS-PAGE to yield three polydisperse peaks with Rf values of 0.31, 0.57, and 0.84. 125I-labeled egg glycoproteins were further fractionated by ion exchange chromatography to yield four peaks or shoulders. One of these peaks constituted the major labeled egg glycoprotein of S. haematobium (MEGL-H) in a relatively pure form as determined by SDS-PAGE, and its estimated m.w. was 70,000. This glycoprotein was consistently and highly reactive serologically with a serum pool from schistosomiasis haematobia patients by a Farr-type radioimmunoassay (RIA). A limited cross-specificity study of inhibition RIA indicated that S. mansoni eggs contain components that cross-react only partially with MEGL-H. These results focus attention on MEGL-H as a potential serodiagnostic probe.

Female↗
PubMed1981

Antigranulocyte antibodies and deranged immune function associated with phenytoin-induced serum sickness.

A phenytoin-associated serum-sickness-like syndrome was followed by severe pancytopenia in a 17-year-old female. Serum obtained during the acute phase of her illness contained antibodies against homologous eosinophils and neutrophils, antibodies against autologous neutrophils, and antibodies to phenytoin. The serum also inhibited bone marrow granulocyte colon formation in vitro. Lymphocyte transformation by pokeweed mitogen was impaired and, after recovery, the patient's lymphocytes were transformed in vitro by the addition of phenytoin. These data demonstrate that profound derangements of immunity can be associated with a phenytoin-induced serum-sickness-like illness.

Adolescent↗
PubMed1981

In vivo suppression of delayed hypersensitivity by thiabendazole and diethylcarbamazine.

Several anthelminthic agents, such as niridazole and metronidazole, have been demonstrated to have striking effects on the immune system, apparently independent of their antiparasitic activities. In the present study, we have examined the effect of thiabendazole and diethylcarbamazine on two parameters of delayed hypersensitivity, lung granuloma formation around Schistosoma mansoni eggs and delayed footpad edema in response to schistosome egg antigens. Both drugs caused significant reduction of lung granuloma size in unsensitized animals when given as daily doses for 8 days. Thiabendazole was the more potent suppressant, affecting granuloma size in unsensitized animals when given as single dose and in sensitized animals using a multiple dose regimen. Diethylcarbamazine was without effect on granuloma size in sensitized animals, but inhibited delayed footpad swelling when given daily for 6 days. Neither drug affected granulomas induced by non-antigenic plastic beads. These data support the hypothesis that some of the clinical activities of these drugs may be mediated by interference with host response to antigenic stimuli.

Animals↗
PubMed1981

Immunopathology of murine infection with Schistosoma mansoni: relationship of genetic background to hepatosplenic disease and modulation.

The influence of genetic factors on the manifestations of disease associated with infection with Schistosoma mansoni (portal hypertension, liver granulomas, hepatosplenomegaly) and their modulation were studied in inbred strains of mice. Three groups were identified according to the degree of portal hypertension: high (portal venous pressure, 19.1 cm H2O: DBA/1J), intermediate (8.9-13.4 cm H2O; BALB/cJ, DBA/2J, CBA/CaJ, C3H/HeJ, and BUB/BnJ), and low responders (6.1 cm H2O; C57BL/6J). Granuloma size, organomegaly, and portal venous pressure were strain dependent and not H-2 dependent and were determined by more than one gene. Studies of schistosomiasis in the F1 generation of high and low responders indicated that more than one gene is involved. Modulation of portal venous pressure between eight and 20 weeks of infection occurred in C57BL/6J but not in BALB/cJ mice and was transferable with immune lymphoid cells. These data indicate that disease associated with infection with S. mansoni and its modulation in mice are influenced by the genetic (non-H-2) background of the host and dependent in part on cell-mediated immunity.

Animals↗
PubMed1981

Role of cell-generated hydrogen peroxide in granulocyte-mediated killing of schistosomula of Schistosoma mansoni in vitro.

Human as well as murine granulocytes have been shown to kill the larval stages of helminth parasites; the mechanism of this cell-mediated cytotoxicity is, however, poorly understood. The present study was designed to assess the role of peroxidative processes in killing of schistosomula of Schistosoma mansoni by human granulocytes in vitro. The rate of H(2)O(2) production by human neutrophils, eosinophils, and basophils was measured upon incubation with schistosomula alone or in the presence of specific antibody or complement. Opsonized parasites (antibody and/or complement) increased the rate of H(2)O(2) production by neutrophils, eosinophils, and basophils by respective percentages of 500, 500, and 371. The rate of H(2)O(2) release was directly related to the number of granulocytes and to the proportion of cells attached to the surface of the schistosomula. Increased hydrogen peroxide release occurred by 10 min of incubation and was demonstrable up to 16 h after addition of leukocytes to schistosomula. The primary source of this oxygen product was found to be the granulocytes adherent to the schistosomula and not those that remained unattached. Hydrogen peroxide production by neutrophils and eosinophils was quantitatively similar (schistosomula coated with antibody plus complement stimulated 5 x 10(6) neutrophils and eosinophils to release H(2)O(2) at respective rates of 0.35 and 0.40 nmol/min). Granulocyte-mediated parasite killing correlated with rate of H(2)O(2) generation; both processes were inhibited by catalase. To define further the role of oxidative metabolites, neutrophils and eosinophils of two subjects with chronic granulomatous disease were used; marked reduction of granulocyte-mediated parasite mortality was observed. Peroxidase was required for H(2)O(2)-mediated killing. Addition of the peroxidase inhibitors azide (1 mM), cyanide (1 mM), or aminotriazole (1 cM) to neutrophilschistosomula mixtures significantly reduced parasite cytotoxicity (P < 0.01); similar reduction was observed when eosinophils were used (P < 0.01). Fixation of halide (iodide) to trichloroacetic acid-precipitable protein (2.4-6.0 nmol/h per 10(7) neutrophils) was demonstrated in the presence of granulocytes, opsonins, and parasites; this process was completely inhibited by 1 mM azide. These data indicate that contact between the surfaces of human granulocytes and schistosomula results in release of cellular hydrogen peroxide and iodination. The generation of H(2)O(2) and its interaction with peroxidase appear to be crucial in effecting in vitro granulocyte-mediated parasite cytotoxicity.

Animals↗
PubMed1981

Peroxidase-mediated toxicity to schistosomula of Schistosoma mansoni.

Guinea pig eosinophil peroxidase (EPO) was capable of killing schistosomula of Schistosoma mansoni in vitro when combined with hydrogen peroxide and a halide. Killing was measured by 51Cr release, by microscopic evaluation of viability, and by reinfection experiments in mice. Parasite killing was dependent on each component of the EPO-H2O2-halide system, was completely inhibited by catalase and azide, and was partially inhibited by cyanide. The EPO-mediated system required 10(-4) M H2O2 and 10(-4) M iodide at pH 7.0, and the schistosomula were killed with exposure to this system of less than 30 min at 37 degrees C. At pH 6.0, the EPO-mediated system showed significant cidal activity with 10(-6) M iodide. Canine neutrophil peroxidase (myeloperoxidase [MPO]) was also able to kill schistosomula in vitro in the presence of 10(-4) M H2O2 and 10(-4) iodide at pH 7.0 and pH 6.0. Physiologic concentrations of chloride (0.1 M) could substitute for iodide at pH 7.0 and pH 6.0 as the halide cofactor; however, at pH 7.0, a higher concentration of enzyme was required. These findings with isolated enzyme systems are compatible with a role for peroxidase in the host defense against schistosomula.

Animals↗
PubMed1981

Quantification, dynamics, and mechanisms of pulmonary inflammatory response around schistosomula of Schistosoma mansoni.

The inflammatory response around schistosomula injected into the lungs of uninfected mice and mice infected with Schistosoma mansoni was quantified. In uninfected mice, the inflammatory response started at 1 hour and peaked at 6 days, whereas in the infected mice, the inflammatory response was accelerated and peaked at 24 hours. This latter inflammatory reaction was 1.5 times greater than the 6-day reaction found in uninfected controls. Neutrophils and mononuclear cells were seen around schistosomula impacted into the pulmonary microvasculature by 1 hour; later, however, eosinophils constituted the predominant cell. This augmented inflammatory response was detected in mice infected with S mansoni first at 4 weeks after injection and peaked at 12 weeks. The augmented response correlated with acquired resistance as assayed by the recovery of the organisms from the lungs 4 days after challenge. Augmented inflammatory reaction and increased protection was induced by subcutaneous sensitization with dead schistosomula or eggs but not by cercariae or adult worms. Adoptive transfer of serum but not lymphoid cells from 12-15 week-infected mice resulted in augmented inflammation and enhanced resistance in recipient normal animals. The serum activity was absorbed by both schistosomula and eggs and was shown to reside in the fraction containing IgG1.

Animals↗
PubMed1981

Dichotomies in the reactivity to worm antigen in human schistosomiasis mansoni.

3H-thymidine incorporation was studied using peripheral blood mononuclear cells (PBMC) from 41 Egyptians with Schistosoma mansoni infection. The individuals were preselected to fall into 3 age-matched categories: asymptomatic with light and heavy infections and those with schistosomal hepatosplenomegaly. Seven uninfected individuals served as controls. PBMC from all groups were comparable in their responsiveness to phytohemagglutinin (PHA), streptokinase-streptodornase (SKSD), and the schistosome soluble egg antigen (SEA). However, DNA synthesis induced by soluble worm antigenic preparation (SWAP) differed significantly among these groups. The mean response to SWAP (delta cpm = experimental cpm minus control cpm +/- standard error) was markedly decreased in individuals with heavy infections (1,963 +/- 509) compared with those with light to moderate egg excretion (4,646 +/- 790; p less than 0.01). Moreover, 2 subgroups were discernible among patients with hepatosplenomegaly. Seven were unresponsive to SWAP (7659 +/- 231), whereas 13 had vigorous responses (14, 617 +/- 2263; p < 0.01). This is the first demonstration of an inverse relationship between specific immune responsiveness to adult worm antigens and intensity of infection in humans with schistosomiasis mansoni. The depressed lymphocyte reactivity in patients with heavy infection, whether cause or consequence of the parasite load, may perpetuate large worm burdens. Furthermore, the observations on patients with hepatosplenomegaly may reflect differing pathogenetic mechanisms.

Adolescent↗
PubMed1980

Role of arginase in killing of schistosomula of Schistosoma mansoni.

Nonspecific resistance to the multicellular organism Schistosoma mansoni can be induced in mice by several infectious agents. We utilized the observed genetic restriction of such acquired resistance to study the mediators of killing of the larval stage of S. mansoni in vitro. Adherent peritoneal cell monolayers from Corynebacterium parvum-treated C57BL/6J but not from C. parvum-treated BALB/cJ mice killed an increased proportion of schistosomula in 24 h. Activated macrophages (Mphi) from both strains exhibited enhanced H(2)0(2) production after incubation with the parasites or phorbol myristate acetate. Thus H(2)0(2) production was not associated with schistosomula killing. Moreover, schistosomula killing was unaffected by catalase or superoxide dismutase. In contrast, activated C57BL/6J (but not BALB/cJ) Mphi released fourfold more arginase into supernates than control Mphi. Schistosomula killing by these Mphi correlated with arginase content of the supernates, was exaggerated in arginine-poor medium, and could be blocked by the addition of arginine. Exogenous bovine arginase added to Fischer's medium without macrophages produced comparable parasite mortality. Our data suggest that arginase is a critical mediator of in vitro killing of this multicellular organism by activated macrophages.

Arginase↗
PubMed1980

The role of eosinophils in granulopoiesis. I. Eosinophilia in neutropenic patients.

The role of eosinophils in granulopoiesis is unclear. In a variety of conditions, the level of eosinophils is inversely related to the level of neutrophils. The present report describes two patients with eosinophilia and neutropenia and examines the in vitro effects of eosinophils on the colony formation of their bone marrow in semisolid culture medium. The addition of autologous eosinophils to bone marrow cultures from these patients resulted in a decrease in the number of colonies; in contrast, antieosinophilic serum increased the number of colony-forming units. Indomethacin, an inhibitor of prostaglandin, was capable of reversing the effects of added eosinophils. The findings suggest that eosinophils have an inhibitory effect on in vitro granulopoiesis. The suppressive effects may be due to the high content of prostaglandin E found in eosinophils. A schematic diagram based on the current knowledge of the mechanism of granulopoiesis is presented.

Aged↗