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Biomedical subjects

S Shai

Publications and source records attributed to S Shai.

7 recordsLinked to original sources
PubMed1995

Epitopes in the 19kDa fragment of the Plasmodium falciparum major merozoite surface protein-1 (PfMSP-1(19)) recognized by human antibodies.

The antibody response to two different epitopes located in the C-terminal 19kDa fragment of the Plasmodium falciparum merozoite surface protein-1 (MSP-1(19)) has been studied using a competitive ELISA based on the inhibition of monoclonal antibody (MoAb) binding by serum samples. Sera from children aged three to eight years who suffered clinical symptoms of malaria, or were partially immune with an asymptomatic infection, and from adults all living in The Gambia, West Africa were tested. The results suggest that the antibody response to MSP-1(19) has a role in naturally-acquired immunity in Gambian individuals.

Adult↗
PubMed1994

Antibodies inhibit the protease-mediated processing of a malaria merozoite surface protein.

When merozoites of the malaria parasite Plasmodium falciparum are released from infected erythrocytes and invade new red cells, a component of a protein complex derived from the merozoite surface protein 1 (MSP-1) precursor undergoes a single proteolytic cleavage known as secondary processing. This releases the complex from the parasite surface, except for a small membrane-bound fragment consisting of two epidermal growth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes. We report that, a group of monoclonal antibodies specific for epitopes within the EGF-like domains, some interfere with secondary processing whereas others do not. Those that most effectively inhibit processing have previously been shown to prevent invasion. Other antibodies, some of which can block this inhibition, not only do not prevent invasion but are carried into the host cell bound to the merozoite surface. These observations unequivocally demonstrate that the binding of antibody to the COOH-terminal region of MSP-1 on the merozoite surface may not be sufficient to prevent erythrocyte invasion, and show that the interaction of different antibodies with adjacent epitopes within the EGF-like domains of MSP-1 can have distinct biochemical effects on the molecule. Inhibition of MSP-1 processing on merozoites may be a mechanism by which protective antibodies interrupt the asexual cycle of the malaria parasite.

Animals↗
PubMed1993

A conserved parasite serine protease processes the Plasmodium falciparum merozoite surface protein-1.

The merozoite surface protein-1 of the human malaria parasite Plasmodium falciparum undergoes an extracellular proteolytic cleavage (secondary processing) intrinsic to successful erythrocyte invasion. In the T9/96 clone of P. falciparum the protease responsible has been characterised as a membrane-associated, calcium-dependent activity, sensitive to irreversible inhibitors of serine proteases. Here we extend these studies and show that secondary processing activity in intact merozoites of P. falciparum strains expressing the alternative dimorphic type of merozoite surface protein-1 has identical characteristics, and that the cleavage site is close to or identical to that in the protein from T9/96. The protease responsible is shown to be parasite-derived, and able to catalyse processing of native substrate only when present in the same membrane. Cleavage of the substrate follows apparent first order kinetics for at least 2 half-lives. It is concluded that secondary processing of both dimorphic forms of the P. falciparum merozoite surface protein-1 is a conserved event, mediated by a mechanistically conserved protease located on the merozoite surface. These observations provide clues to the identity of the protease and show that, irrespective of the dimorphic type, secondary processing results in the same, highly conserved region of the merozoite surface protein-1 remaining on the surface of the invading merozoite.

Animals↗
PubMed1992

Identification of human sperm antigens reacting with antisperm antibodies from sera and genital tract secretions.

OBJECTIVE: To identify sperm antigens reacting with antisperm antibodies relevant in human infertility. DESIGN: The reactions of separated sperm antigens with antibodies present in sera and genital tract secretions from infertile and fertile females and males were examined by immunoblotting techniques. SETTING: The patients were followed in an outpatient setting of a hospital clinic. PATIENTS: One hundred consecutive infertile males and females, referred for determinations of antisperm antibodies, comprised the study group. Fifty hospital and faculty employees with proven fertility served as a control group. RESULTS: A high proportion of sera from fertile and infertile humans contained antibodies reacting with at least one sperm antigen. However, two discrete bands of antigenic proteins with molecular weights of 44 and 72 kd reacted significantly more frequently with serum antibodies from infertile females than from fertile females. No apparent correlation could be demonstrated between any particular antigen and serum antibodies from infertile males. Nevertheless, antigenic proteins of 62 kd were identified as the major sperm antigens reacting with antibodies present in seminal plasmas from infertile males. CONCLUSIONS: The major sperm antigens reacting with systemic antibodies differ from the antigens recognized by local antisperm antibodies. Sperm antigens exhibiting relative molecular weights of 62 kd are major antigens reactive with local antisperm antibodies from infertile humans.

Autoantibodies↗
PubMed1992

A malaria merozoite surface protein (MSP1)-structure, processing and function.

Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.

Amino Acid Sequence↗
PubMed1990

A reverse (antibody capture) enzyme-linked immunosorbent assay for detection of antisperm antibodies in sera and genital tract secretions.

A reverse (antibody capture) enzyme-linked immunosorbent assay (ELISA) for detection of antisperm antibodies has been developed. The assay enables detection of immunoglobulin (Ig) M, IgG, IgA, or IgM, IgG, and IgA--antisperm antibodies in serum, cervical mucus, and seminal plasma samples. The reverse ELISA is more specific and sensitive than conventional ELISA in detecting human antisperm antibodies of different isotypes. Using this assay, statistically significant differences in levels of antibodies between infertile and fertile individuals were demonstrated in sera and in genital tract secretions. Studies with 143 infertile couples revealed that the presence of antibodies in sera was not necessarily reflected in individual's genital tract secretion and vice versa. These data emphasize the importance of detecting antisperm antibodies in sera as well as in genital tract secretions for correct evaluation of sperm immunity.

Adult↗