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Biomedical subjects

P O Ali

Publications and source records attributed to P O Ali.

8 recordsLinked to original sources
PubMed1991

Sequence of a small subunit rRNA gene of Schistosoma mansoni and its use in phylogenetic analysis.

The complete sequence of a small ribosomal RNA gene of Schistosoma mansoni contained within plasmids pSM389 and pSM889 is presented. It was found to be 1992 bp in length, larger than that of most eukaryotes. Extra nucleotides occur in regions known to be variable (V4 and V7). The predicted secondary structure of the nucleotides 660-853 revealed additional helices which have been designated E21-1A and E21-1B. The other region to differ from higher eukaryotes lies between nucleotides 1457 and 1569. Secondary structure prediction demonstrated that a single extended helix may be formed from this part of the schistosome small subunit rRNA sequence. Nucleotides that could be unambiguously aligned with those of 12 other eukaryotes were used to estimate phylogenetic relationships. The consensus tree obtained by Maximum Parsimony analysis showed the schistosome as a sister taxon to the flatworm Dugesia tigrina.

Amino Acid Sequence↗
PubMed1991

Structure of Sm25, an antigenic integral membrane glycoprotein of adult Schistosoma mansoni.

Sm25 is the principal antigen recognised by antibodies from mice protectively vaccinated with isolated tegumental membranes of adult Schistosoma mansoni. The full-length amino acid sequence of this protein has been deduced from the sequence of two cDNAs, one isolated by screening a cDNA library and the other, including the 5' end of the gene, amplified directly from adult worm RNA using the polymerase chain reaction. The predicted sequence represents a nascent polypeptide of Mr 21,500. Following cleavage of a predicted signal sequence, the Mr of the resulting polypeptide is 17,600. The polypeptide contains 2 potential sites for N-linked glycosylation and a hydrophobic domain at the C-terminus that could facilitate membrane association. Analysis of the mature gene product confirmed that Sm25 is an N-glycosylated integral membrane protein and that the Mr of the deglycosylated polypeptide is between 15,000 and 20,000.

Amino Acid Sequence↗
PubMed1989

Protective immunization of mice against Schistosoma mansoni with purified adult worm surface membranes.

Immunity to Schistosoma mansoni in the mouse was induced by vaccination with adult worm surface membrane (mb-S). Of several adjuvants tested, including Freund's, BCG and alum, 50 micrograms of saponin per mouse given subcutaneously with the antigen was the easiest to administer, and gave consistent protection, approaching levels usually seen in our mouse model after exposure to irradiated cercariae. An antibody response to the schistosomular surface was detected in mice immunized with mb-S plus saponin which was predominantly anti-polypeptide, not anti-carbohydrate, and thus similar to the antibody response of mice exposed to irradiated cercariae. The level of antibodies to Mr 90,000 and 38,000 schistosomular surface antigens as well as to Mr 25,000 adult surface membrane antigen was significantly correlated with the presence of protection.

Adjuvants, Immunologic↗
PubMed1989

Serological differentiation of acute and chronic schistosomiasis mansoni by antibody responses to keyhole limpet hemocyanin.

The existence of a shared epitope between the hemocyanin of the marine mollusk Megathura crenulata, better known as the keyhole limpet, and schistosomula has been reported. This epitope has been shown to be a major immunogen in human infection. In this study, keyhole limpet hemocyanin (KLH) was used to measure antibodies recognizing the cross-reacting epitopes in sera from patients with acute and chronic schistosomiasis using an enzyme-linked immunosorbent assay (ELISA). Marked differences in IgG and IgM antibody response were noted between acutely and chronically infected patients at a reciprocal serum dilution of up to 2,560. The acute sera had a mean +/- SD OD490 nm values for IgG and IgM of 1.0 +/- 0.44 and 1.34 +/- 0.6 compared to mean +/- SD IgG and IgM absorbance for the chronic sera of 0.22 +/- 0.10 and 0.22 +/- 0.11 respectively. Setting our lowest positive limit at greater than 2 SD above the mean of the chronic sera, 28 of the 30 patients previously diagnosed as having acute schistosomiasis were correctly identified by their IgG and IgM response. Of 5 patients studied longitudinally, IgG persisted at the same levels 10-13 weeks after treatment. IgM levels, on the other hand, showed a tendency to decrease but remained above the established cut-off level. This study provides further evidence for the association of schistosomulum surface carbohydrate antibody with acute infection and demonstrates the ability of a simple non-competitive ELISA using microtiter plates coated with minute quantities of KLH to differentiate serologically between cases of acute and chronic schistosomiasis.

Acute Disease↗
PubMedDate not supplied

Antibody to schistosomulum surface carbohydrate epitopes in subjects infected with Schistosoma haematobium.

The binding of immunoglobulin to carbohydrate epitopes on the surface of Schistosoma mansoni schistosomula was measured with 125I-labelled protein A in sera from 67 Gambian subjects living in a focus of intense S. haematobium transmission. The levels of such antibody differed considerably between subjects and there was significant variation between age groups. The highest mean level, in subjects aged between 8 and 14 years, was significantly greater than that in older subjects. Previous studies have shown that resistance to post-treatment reinfection with S. haematobium is related to age in this focus, and is greatest in those aged 15 or more years. These differing relationships with age suggest that antibodies directed against carbohydrate epitopes on the surface of the schistosomulum do not have a major protective role in man.

Adolescent↗
PubMedDate not supplied

Dissociation of antibody responses during human schistosomiasis and evidence for enhancement of granuloma size by anti-carbohydrate IgM.

Immunoglobulin (Ig) G and IgM antibody levels to soluble egg antigens (SEA), adult worm glycoproteins (AWGP), carbohydrate antigens (CHO) and cationic exchange fraction 6 (CEF6) were measured in serum specimens taken from Brazilian patients with acute, intestinal, hepato-intestinal and hepatosplenic schistosomiasis mansoni. The antibody levels varied among the groups, with the highest anti-egg antigen responses in the acute patients and the highest anti-adult worm responses in patients with chronic disease. The responses to the component parts of the egg antigens were dissociated, with anti-carbohydrate IgG and IgM responses being highest in the acute infection group and anti-CEF6 IgG responses being uniform among the clinical groups. The possibility of a direct role for anti-CHO antibody responses in egg-induced pathology was investigated using the mouse lung model. The anti-carbohydrate monoclonal antibody NIMP/M45 significantly enhanced granuloma formation. Mice given NIMP/M45 produced granulomas larger than those of naive mice or mice given an unrelated monoclonal antibody, and as large as those produced by mice which had been presensitized to egg antigens. The independent regulation of responses to egg antigens may indicate that such responses are minimized to reduce the pathological consequences of infection whilst allowing the development of protective anti-worm responses.

Acute Disease↗