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Biomedical subjects

M J Lockyer

Publications and source records attributed to M J Lockyer.

15 recordsLinked to original sources
PubMed1993

A humanized CD18 antibody can block function without cell destruction.

Leukocyte integrins are intimately involved in transient adherence of leukocytes to endothelium and to each other in the processes of extravasation and cell activation. In this study, seven mAb directed against human CD11a and two mAb directed against human CD18, the alpha- and beta-chains of the leukocyte functional Ag-1 molecule, respectively, were analyzed for their ability to inhibit several leukocyte functional Ag-1-mediated interactions. The best blocking mAb in these studies, a rat anti-human CD18, YFC51.1, was subsequently humanized by complementarily-determining region grafting, associated with human C regions and expressed. The humanized mAb was shown to maintain binding for human CD18. Even though the humanized mAb was an IgG1 isotype it still retained the functional blocking characteristics of the rat mAb while failing to mediate cell killing. The IgG1 mAb was unable to bind human Clq and could block but did not mediate antibody-dependent cellular cytotoxicity.

Animals↗
PubMed1993

Immunogenicity of a hybrid Plasmodium falciparum malaria antigen.

A recombinant baculovirus-expressed hybrid protein containing epitopes for the C-terminal fragment of the Plasmodium falciparum precursor to the major merozoite surface antigens (PMMSA) and the tetrapeptide repeats of the circumsporozoite protein (CSP) was assessed for its immunogenicity. Murine MHC-II restriction of the antibody response to the CSP repeats was not overcome by the PMMSA component, the response to which showed no restriction. In an adjuvant trial the highest antibody titres in rabbits to both components of the hybrid were obtained using Freund's adjuvant. Lack of a boosting antibody response to the CSP repeats appeared to be linked to the conformation of the PMMSA component. Formulation of the hybrid protein into Iscoms gave antibody titres of only short duration to both components.

Adjuvants, Immunologic↗
PubMed1991

Prevalence of multiple sclerosis in five rural Suffolk practices.

OBJECTIVE: To determine a point prevalence of multiple sclerosis in part of Suffolk. DESIGN: Multiple source search for patients with multiple sclerosis in five general practices. Patients were reviewed and categorised by using general practice notes. SETTING: Five rural general practices in Suffolk, 12 May 1988. SUBJECTS: 31,379 patients registered with five practices. MAIN OUTCOME MEASURES: Multiple sclerosis diagnosed by a specialist. RESULTS: The search produced a provisional list of 62 eligible patients with multiple sclerosis. Review of case notes showed that 48 had probable disease, 10 early disease, and four possible disease. The probable cases gave a crude prevalence of 153/100,000 population (95% confidence interval 109/100,000 to 196/100,000). CONCLUSIONS: Although the results should be interpreted cautiously because of the small sample size, they suggest that the prevalence of multiple sclerosis in Suffolk is higher than has been estimated from hospital data.

Age Factors↗
PubMed1989

Wild isolates of Plasmodium falciparum show extensive polymorphism in T cell epitopes of the circumsporozoite protein.

Variation in the immunodominant T cell epitopes Th2R and Th3R of the Plasmodium falciparum circumsporozoite protein has been analysed from Gambian clinical isolates using the polymerase chain reaction. The degree of polymorphism in these epitopes is more extensive than that found in several geographically diverse laboratory isolates. These findings strongly suggest that it will not be feasible to include all variants in a polyvalent subunit sporozoite vaccine.

Amino Acid Sequence↗
PubMed1988

An S antigen gene from Plasmodium falciparum contains a novel repetitive sequence.

The complete sequence of the gene coding for the S antigen from the Wellcome (West African) strain of Plasmodium falciparum has been obtained. It contains a central repetitive region consisting of 65 copies of a partially degenerate 24 bp sequence, coding for a conserved 8 amino acid repeat (Gly Pro Asn Ser Asp Gly Asp Lys). The repeat sequence is different from those of S antigens characterised in other strains and thus represents a new S antigen serotype.

Amino Acid Sequence↗
PubMed1988

A hybrid gene to express protein epitopes from both sporozoite and merozoite surface antigens of Plasmodium falciparum.

The DNA coding for parts of the repetitive amino acid sequence of Plasmodium falciparum circumsporozoite protein has been spliced to a sequence encoding part of the precursor to the major merozoite surface antigens, to produce a hybrid gene. Expression in Escherichia coli produces a protein with antigenic determinants from both malaria proteins. Antibodies raised against the expressed material react with both a peptide derived from the circumsporozoite repeat sequence, and the merozoite surface molecule. Hybrid molecules of this type may be the basis of a malaria vaccine.

Amino Acid Sequence↗
PubMed1987

Strain variation in the circumsporozoite protein gene of Plasmodium falciparum.

The complete nucleotide sequence of the cloned circumsporozoite protein gene of the Plasmodium falciparum Wellcome (West African) isolate has been determined. The sequence shows two striking differences from that of the published Brazilian strain; the total number of tandem 12 base pair repeats is 46 compared to 41, and the 5' coding region contains an additional 30 nucleotides. From Southern blot experiments, two out of four cloned Thai lines also have a similar, higher number of repeats. Heterogeneity in the CSP gene repeat region and in the length of the 5' coding region allows the strains to be classed into three groups, with the Wellcome strain being indistinguishable from the Thai line T9-94.

Animals↗
PubMed1987

Processing of the precursor to the major merozoite surface antigens of Plasmodium falciparum.

Specific sequences derived from the gene for the precursor to the major merozoite surface antigens (PMMSA) of Plasmodium falciparum have been expressed in Escherichia coli and the products have been used to produce antibodies. These antibodies, together with monoclonal antibodies, have been used to investigate the form of the PMMSA protein associated with merozoites. Polypeptide fragments derived by processing from the PMMSA protein have been detected in extracts of merozoites and assigned to locations within the PMMSA coding sequence.

Animals↗
PubMed1986

Structural diversity of the major surface antigen of Plasmodium falciparum merozoites.

The structures of the major merozoite surface antigen of Plasmodium falciparum and the gene encoding it were indistinguishable for the Wellcome strain and the Thai clone T9/94 but different for clones T9/96, T9/98, and T9/101. The central portion of the gene is subject to the greatest variation in structure. The protein from all five lines was found to be posttranslationally modified by covalent addition of both carbohydrate and fatty acid.

Animals↗
PubMed1984

Expression of cloned cDNA for a major surface antigen of Plasmodium falciparum merozoites.

A cDNA library of P. falciparum was constructed. Using size-selected mRNA as a probe several clones were isolated which hybridized to mRNAs larger than 5 kilobases (kb). The cDNA insert of pFC 17, which hybridizes to 5.6-kb mRNA was expressed by fusion to anthranilate synthetase I in a plasmid expression vector. The expressed fusion protein was shown to contain epitopes of a 195-kDa protein which is the precursor to 3 major surface antigens of P. falciparum merozoites.

Animals↗
PubMed1984

Cloning of malarial genes coding for high molecular weight antigens: isolation of fragments of Plasmodium falciparum genes coding for proteins of 145 000 molecular weight.

RNA preparations from Plasmodium falciparum were shown to direct the cell free synthesis of many high molecular weight proteins, some of which could be immunoprecipitated by sera from humans immune to P. falciparum. Among these was an abundant protein with a molecular weight of 145 000. Messenger RNAs coding for high molecular weight antigens were enriched by size fractionation and used after reverse transcription to identify genomic restriction fragments in Southern blots. Genomic restriction fragments were cloned into plasmid and phage lambda vectors. Two recombinants which were recognized by the high molecular weight probe were characterized by hybrid-select-translation. In both cases the predominant in vitro translation products were proteins with a molecular weight of 145 000.

Animals↗
PubMedDate not supplied

Primary structure of the precursor to the three major surface antigens of Plasmodium falciparum merozoites.

Recently, a class of protein antigens of high relative molecular mass (Mt) which can induce protective immunity against blood-stage malaria has been identified. In Plasmodium falciparum the protein has a Mr of approximately 195,000 (P195). It is the precursor of three proteins of Mr 83,000 (83K), 42K and 19K which are the major surface antigens of merozoites; thus it may also be useful for immunization against P. falciparum. Three studies describing the isolation of single short complementary DNA clones for part of the P195 gene sequence have been reported. Here we describe the complete structure of the P195 gene determined from further DNA clones, its organization within genomic DNA and the location of the specific processing fragments within the primary amino-acid sequence.

Amino Acid Sequence↗