PubMed Health⌕ Search

Biomedical subjects

A A Mahmoud

Publications and source records attributed to A A Mahmoud.

At least 55 records · Page 3Linked to original sources
PubMed1989

Entamoeba histolytica depresses chemiluminescence in stimulated human polymorphonuclear leukocytes.

Effect of Entamoeba histolytica proteinase/toxin (Ehp/t) on the luminol-dependent chemiluminescence (CL) in stimulated human polymorphonuclear leukocytes (PMN) was studied. The role of superoxide (SO) and hydroxyl (OH) anions in the Ehp/t-associated enhancement/inhibition of CL was also studied using specific scavengers and a biological response modifier, muramyldipeptide (MDP). Ehp/t was isolated from axenic trophozoites of the HM-1:IMSS strain of virulent strain of E. histolytica. Proteinase activity was assayed on a synthetic substrate, Z-arg-arg-AFC and cytotoxicity was tested on HeLa cell monolayers. PMN isolated from blood were incubated with Ehp/t prior to stimulation by phorbol myristateacetate (PMA, 2 micrograms/ml), serum-treated zymosan (2.5 mg/ml) and glucan (2 mg/ml). CL was monitored in an LKB (Wallac) Luminometer. Ehp/t was found to depress up to 90% of CL induced by PMA, glucan and zymosan. Such a depression was Ehp/t concentration-dependent. A 150 micrograms/ml concentration of Ehp/t, obtained from a 0.015-1.5 mg/ml concentration range tested at different incubation times and temperatures, was used in most of our experiments. Incubation time and temperature optima were 15 min and 37 degrees C, respectively. Ehp/t partially inhibited the CL associated with SO and OH. MDP, in the presence of Ehp/t, enhanced CL response in human PMN to about 67% with reference to normal CL without inhibitor. PMN were confirmed to play a vital role in amebic tissue invasion mechanisms.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Intensity of Schistosoma mansoni infection in a human population is inversely correlated with antibody response to SmW68, a protective parasite antigen.

Vaccination with SmW68, a Schistosoma mansoni surface antigen, significantly protects mice against challenge infection. To investigate the vaccine potential of SmW68 in clinical schistosomiasis, human antibody response to SmW68 was studied as a function of intensity of infection in a chronically infected Egyptian population. In 85 serum samples obtained randomly from families in El Gazairy (population 1,310), antibody to SmW68 (determined by ELISA) was found to increase significantly with age, reaching a plateau at 15-19 y, 1-5 y after peak prevalence and intensity of infection. Among infected individuals (n = 54), antibody response showed a significant inverse correlation (r = -.28, P less than .04) with intensity of infection. In isotype analysis, a higher IgM but not IgG response was significantly associated with low parasite burden. These studies demonstrate that significant antibody response to SmW68 could occur in chronically infected humans. Whether parasite burdens suppress circulating levels of antibody to SmW68 or whether enhanced antibody response to SmW68 represents acquired protective humoral immunity remains to be determined.

Adolescent↗
PubMed1989

Induction of resistance to Schistosoma mansoni infection in mice by purified parasite paramyosin.

Freeze-thaw (FT)-disrupted schistosomula or their membrane extract induced significant resistance in mice to Schistosoma mansoni infection (34 and 25%, respectively) without the use of adjuvant. Antigens identified in schistosome extracts by sera from immunized animals were then evaluated for protective potential. Immunization with schistosomal antigens of 97 and 68-70 kD resulted in significant protection that was equivalent to that obtained by FT schistosomula. Since the 97-kD antigen was suggested to be parasite paramyosin, we used a biochemical technique to purify this muscle protein. Purified schistosome paramyosin ran as a single band on 10% SDS-PAGE and was recognized both by sera from mice immunized with FT schistosomula and a polyclonal antiserum raised against the 97-kD parasite protein. Preincubation of schistosome paramyosin with sera from mice immunized with FT schistosomula resulted in the removal of reactivity with the 97-kD protein in crude worm extracts. Paramyosin was identified by Western blotting to be in the tegument of schistosomula. The purified schistosome paramyosin resulted in significant protection in three separate experiments (24, 46, and 53%) without the use of adjuvant. Addition of BCG to paramyosin resulted in enhanced protection.

Animals↗
PubMed1989

Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya.

To assess the efficacy of low dose praziquantel regimens in comparison with standard 40 mg/kg dosing in the treatment of urinary schistosomiasis, a random allocation dose-finding trial was performed in children and adults from a Schistosoma haematobium endemic region in Coast Province, Kenya. Following an initial screening, 280 individuals with greater than or equal to 50 eggs/10 ml urine were randomly assigned to receive either 10, 20, 30, or 40 mg/kg of the drug in a single oral dose. Two to three months later, cure rates of 26%, 68%, 78%, and 84% were found for the 10, 20, 30, and 40 mg/kg doses, respectively. The results of 10 mg/kg oral dosing were significantly worse than for all other doses in terms of cure rate and of post-treatment prevalence of morbidity. The 40 mg/kg dosing resulted in a significantly higher cure rate than the 20 mg/kg doses; nevertheless, there was no significant difference between 20 mg/kg and 40 mg/kg doses in terms of mean post-treatment intensity of infection or post-treatment prevalence of hematuria or proteinuria. For large-scale control programs, oral 20 mg/kg praziquantel therapy for urinary schistosomiasis may prove as effective as the standard oral 40 mg/kg dosing for control of infection-associated morbidity and reduction of parasite transmission.

Adolescent↗
PubMed1989

Effects of borehole wells on water utilization in Schistosoma haematobium endemic communities in Coast Province, Kenya.

To determine the impact of the introduction of borehole wells on water use patterns and the consequent risk of transmission of Schistosoma haematobium in 3 endemic villages in Kenya, we performed a survey (a 1:6 sample of affected households) to identify sources of water and types of water utilization before and after well introduction. Water usage was also determined in 2 unaffected neighboring villages not given borehole wells, but having continuous access to piped water from communal taps. Prior to borehole well construction, significantly more high-risk water use occurred in the borehole villages vs. comparison villages in terms of water gathered for cooking, drinking, dish washing, and bathing; residents of both types of villages preferred high-risk sources (marshes and ponds) for clothes washing. Following well introduction, there were significant declines in the use of high-risk water for drinking, cooking, and dish washing, but not for bathing or clothes washing. A higher proportion of individuals from the 3 borehole villages reported some type of continued contact with high-risk water sources. Despite well introduction and a 3 year chemotherapy program among school-aged children, a 21-28% incidence of infection persisted among children in the villages, suggesting minimal impact on transmission. Regular monitoring for S. haematobium infected snail sites showed no decline in the number or proportion of infected snails. Borehole well introduction can significantly alter some forms of water usage, but social and water quality factors may limit the ability of communal wells to reduce S. haematobium transmission.

Adult↗
PubMed1989

Effect of Leishmania major on luminol-dependent chemiluminescence of human whole blood phagocytosis.

The aim of this study is to examine the effect of L. major on human whole blood phagocytosis. The phagocytosis was activated by phorbol myristate acetate (PMA) or opsonized zymosan. Various types of Leishmania antigens were tested on luminol-dependent chemiluminescence. In PMA-activated whole blood phagocytosis group, promastigotes and infected medium significantly (P less than 0.001) depressed the maximum peak of chemiluminescence to 5.77 +/- 1.6 and 5.65 +/- 0.45 mV respectively, compared to 9.85 +/- 22 in control group. In a similar fashion a significant reduction of the area under the curve was noted. On the other hand, opsonized zymosan-activated phagocytosis was significantly (P less than 0.025) inhibited in the promastigote treated group only. The maximum peak response was 4.68 +/- 1.5 and 10.8 +/- 0.46 mV in promastigote and control groups, respectively. The above data indicated; a) an inhibition of whole blood phagocytosis induced by Leishmania and b) a marked reduction of the oxygen-reactive metabolites radicals generated by whole blood phagocyte cells and measured by luminol-dependent chemiluminescence suggesting the important role of oxygen free radicals in the pathogenesis of leishmaniasis.

Animals↗
PubMed1988

Characterization of [3H]palmitate- and [3H]ethanolamine-labelled proteins in the multicellular parasitic trematode Schistosoma mansoni.

Biosynthetic labelling experiments with cercariae and schistosomula of the multicellular parasitic trematode Schistosoma mansoni were performed to determine whether [3H]palmitate or [3H]ethanolamine was incorporated into proteins. Parasites incorporated [3H]palmitate into numerous proteins, as judged by SDS/polyacrylamide-gel electrophoresis and fluorography. The radiolabel was resistant to extraction with chloroform, but sensitive to alkaline hydrolysis, indicating the presence of an ester bond. Further investigation of the major 22 kDa [3H]palmitate-labelled species showed that the label could be recovered in a Pronase fragment which bound detergent and had an apparent molecular mass of 1200 Da as determined by gel filtration on Sephadex LH-20. Schistosomula incubated with [3H]ethanolamine for up to 24 h incorporated this precursor into several proteins; labelled Pronase fragments recovered from the three most intensely labelled proteins were hydrophilic and had a molecular mass of approx. 200 Da. Furthermore, reductive methylation of such fragments showed that the [3H]ethanolamine bears a free amino group, indicating the lack of an amide linkage. We also evaluated the effect of phosphatidylinositol-specific phospholipase C from Staphylococcus aureus: [3H]palmitate-labelled proteins of schistosomula and surface-iodinated proteins were resistant to hydrolysis with this enzyme. In conclusion, [3H]palmitate and [3H]ethanolamine are incorporated into distinct proteins of cercariae and schistosomula which do not bear glycophospholipid anchors. The [3H]ethanolamine-labelled proteins represent a novel variety of protein modification.

Amino Acids↗
PubMed1988

Paramyosin and actin in schistosomal teguments.

Schistosomes are blood-dwelling trematode parasites that infect 200 million people in developing countries. The critical role served by the tegument in immune evasion and parasite homeostasis suggests that a detailed knowledge of tegumental components would be helpful in the design of new drugs and the production of vaccines. We demonstrate here, by immunoelectron microscopy, that the cytoskeletal proteins actin and paramyosin are organized into major tegumental structures of Schistosoma mansoni. The surface spines are composed of paracrystalline arrays of actin filaments. Actin is also present in areas recovering from damage, implying an important role for this structural protein in tegumental repair. Paramyosin exists predominantly in the tegument in a non-filamentous form, the membrane-bounded elongate bodies. The localization of this protein to the tegument of the parasite is the likely basis for resistance to S. mansoni observed in mice immunized with paramyosin (refs 1, 2 and T. P. Flanigen et al., in preparation).

Actins↗
PubMed1988

Effect of chemotherapy on hepatic collagen and glycosaminoglycan metabolism in Schistosoma mansoni-infected mice.

The dynamics of biosynthesis and accumulation of collagenous proteins and glycosaminoglycans (GAGs) in liver granulomas induced by eggs of Schistosoma mansoni were studied in mice following eradication of adult worms by chemotherapy. The relatively synchronous granulomas around parasite eggs were isolated from the livers at ensuing 2-week intervals; the number of recoverable granulomas per liver gradually decreased and was 7% of initial values at 20 weeks. Hepatic or granuloma-associated extracellular matrix components increased for 4 weeks after treatment despite cessation of ova deposition. At 12 weeks after chemotherapy the rate of GAG biosynthesis per total liver granuloma fraction, measured by 3H-glucosamine incorporation, decreased dramatically; this was followed by a decrease in the amount of GAGs present. The rate of collagen biosynthesis per total liver granuloma fraction, measured by 3H-proline incorporation, began to decline at 14 weeks and a decrease in the amount of collagen present was noted at 16 weeks. Our results demonstrated that liver granulomas induced by S. mansoni eggs synthesize collagens and GAGs for about 4-6 weeks following parasitological cure. The subsequent resolution of granulomas proceeds first by a reduction in GAG biosynthesis followed 4-8 weeks later by decreased collagen biosynthesis, followed by accelerated resolution of both collagen and GAGs.

Animals↗
PubMed1988

Inhibition of surface membrane maturation in schistosomula of Schistosoma mansoni.

The surface membrane of the multicellular parasite Schistosoma mansoni is radically reorganized during the transformation of cercariae into schistosomula. The current study investigates factors involved in maturation of the surface from a trilaminate to a multilaminate membrane. When maturation was induced in the presence of puromycin (900 microM), the acquisition of a multilaminate surface and stainability with fluorescein-conjugated Con A were similar to that of control parasites. Similarly, although organisms treated with monensin (0.1 microM) for 3 hr showed large vacuoles in the perinuclear cytoplasm of the subtegumental cells, the surface membrane became multilaminate. In contrast, microtubule-active drugs interfered with maturation: the surface remained largely trilaminate and the percentage of organisms binding Con A to their surface was significantly reduced. Furthermore, large accumulations of multilaminate bodies were found in the subtegumental cells of colchicine-treated parasites, whereas few were seen in the controls. Colchicine-treated schistosomula failed to mature to adult worms upon injection into mice and, like cercariae, they were water tolerant. We therefore conclude that the components that constitute the schistosomula surface preexist in cercariae and suggest that they are stored in multilaminate bodies before being transported to the surface with the help of microtubules. The acquisition of the multilaminate membrane may be essential for survival of the parasites in vivo and in vitro.

Animals↗
PubMed1988

Urinary tract morbidity in schistosomiasis haematobia: associations with age and intensity of infection in an endemic area of Coast Province, Kenya.

To gain better understanding of the natural history of Schistosoma haematobium associated disease, age- and intensity-related urinary tract morbidity were assessed in a cross-sectional study of Kilole (population 719) in Coast Province, Kenya. Overall prevalence of infection was 65% (39% light, 16% moderate, 9% heavy). Infection prevalence and mean intensity of infection were highest in the 5-14-year-old bracket for both sexes. Although significant intensity-associated increases in hematuria prevalence were noted for both children and adults in all infection categories, hematuria was more common in those less than 15 years of age. Children had a significant increase in the prevalence of dysuria at higher levels of infection, whereas adults did not. Radiographic study of a 1:9 random sample, stratified for age, revealed a greater prevalence of urinary tract granulomas in those less than 15 years. Subjects greater than 15 years of age had a greater frequency of hydronephrosis. Hydronephrosis, hydroureter, and bladder calcification were not associated with higher infection intensity. Among individuals with bladder calcification, a potential marker of cumulative inflammation, 87% had hydronephrosis or hydroureter, compared to a 40% prevalence among individuals without bladder calcification. These findings suggest that certain structural forms of urinary tract disease, such as hydronephrosis, progress during the course of untreated schistosomiasis haematobia despite age-related reductions in egg burden, whereas other forms of morbidity, such as hematuria, remain sensitive to the level of urinary egg excretion at the time of diagnosis.

Adolescent↗
PubMed1987

Isolation and characterization of a protective antigen for adjuvant-free immunization against Schistosoma mansoni.

A single, 68,000 m.w. glycoprotein antigen from adult Schistosoma mansoni was purified by immunoaffinity chromatography with the use of a newly developed, protective, anti-schistosome murine monoclonal antibody. Immunization with two doses of 0.5 microgram or 1 microgram of purified antigen, without adjuvants, afforded a mean 28% reduction in parasite recovery in CF1 mice, and 2-% reduction in parasite BALB/c mice. On immunoblotting, the 68,000 m.w. antigen was common to S. mansoni adults and schistosomula, whereas parasite eggs contained only cross-reacting low m.w. antigens of 19,100 and 16,000. Immunization resulted in the development of anti-antigen antibody and enhanced immediate cutaneous hypersensitivity to the 31-3B6 antigen. By contrast, delayed-type hypersensitivity and sensitization to circumoval granuloma formation were not observed in immunized mice. It was concluded that the 68,000 m.w. 31-3B6 antigen represents a candidate vaccine for adjuvant-free immunization against S. mansoni.

Animals↗
PubMed1987

Effect of glucan on Leishmania major infection in BALB/c mice.

The effect of glucan on Leishmania major infection was studied in BALB/c mice, which are highly susceptible to leishmania infection. Glucan (0.45 mg), or isovolumetric dextrose, was administered intraperitoneally 7, 5, 3 and 1 day before infection with L. major promastigotes. At 3, 5, 6, 8 and 10 weeks after infection, animals were killed; the liver and spleen of each animal were weighed and the parasite burden was calculated. A significant (p less than 0.01) reduction in amastigote proliferation in liver and spleen of animals pretreated with glucan was demonstrated 4, 6 and 8 weeks after infection.

Animals↗
PubMed1987

Monoclonal antibody characterization of a chymotrypsin-like molecule on neutrophil membrane associated with cellular activation.

Monoclonal antibody 1-15 (Ab 1-15), is a murine anti-human neutrophil (PMN) IgG1 that inhibits PMN effector responses to N-formyl-met-leu-phe (FMLP) and phorbol myristate acetate. In this study, the effects of Ab 1-15 on PMN membrane-related functions were characterized: Ab 1-15 inhibited PMN superoxide (O-2) response to FMLP by 60% (P less than 0.005) without effect on the onset or duration of O-2 production. This inhibition of O-2 response was associated with a significant inhibition of PMN chymotrypsin-like, but not trypsin-like, protease activity. Cell fractionation studies indicated the presence of an Ab 1-15 inhibitable, chymotryptic neutral protease activity in PMN membranes. In studies of Ab 1-15 effects on membrane-related second messenger pathways, Ab 1-15 augmented both FMLP- and isoproterenol-induced intracellular cAMP accumulation, whereas alpha-chymotrypsin decreased PMN cAMP response to these stimuli. Our data suggest that the function-inhibiting, anti-PMN monoclonal Ab 1-15 defines a PMN chymotryptic enzyme on the membrane surface that is involved in regulation of two membrane-related functions, O-2 generation and cAMP generation.

Antibodies, Monoclonal↗
PubMed1986

Association of HLA class I antigens (A1, B5, B8 and CW2) with disease manifestations and infection in human schistosomiasis mansoni in Egypt.

The present study was designed to examine the possible association of HLA antigens and schistosomal hepatosplenomegaly and colonic polyposis in a large number of patients and controls. The results show that hepatosplenomegaly was significantly associated with the presence of two HLA antigens: HLA-A1 and B5; and colonic polyposis to HLA-B5 and B8. Furthermore, asymptomatic infection was significantly seen more in subjects with CW2. These results point to possible gentic factors controlling the pathogenesis of disease and susceptibility to infection in human schistosomiasis.

Adolescent↗