scholarly journals Serine Repeat Antigen (SERA5) Is Predominantly Expressed among the SERA Multigene Family ofPlasmodium falciparum, and the Acquired Antibody Titers Correlate with Serum Inhibition of the Parasite Growth

2002 ◽  
Vol 277 (49) ◽  
pp. 47533-47540 ◽  
Author(s):  
Sayaka Aoki ◽  
Jie Li ◽  
Sawako Itagaki ◽  
Brenda A. Okech ◽  
Thomas G. Egwang ◽  
...  
Keyword(s):  
Multigene Family ◽  
Parasite Growth ◽  
Ofplasmodium Falciparum ◽  
Antibody Titers ◽  
Serum Inhibition

scholarly journals Antibodies Reactive with the N-Terminal Domain ofPlasmodium falciparum Serine Repeat Antigen Inhibit Cell Proliferation by Agglutinating Merozoites and Schizonts

1999 ◽  
Vol 67 (4) ◽  
pp. 1821-1827 ◽  
Author(s):  
Xin-Li Pang ◽  
Toshihide Mitamura ◽  
Toshihiro Horii
Keyword(s):  
Recombinant Protein ◽  
Parasitophorous Vacuole ◽  
Parasite Growth ◽  
Specific Antibodies ◽  
Terminal Domain ◽  
Rbc Membrane ◽  
Ofplasmodium Falciparum ◽  
Vaccine Candidate Antigen ◽  
Specific Igg

ABSTRACT The serine repeat antigen (SERA) is a vaccine candidate antigen ofPlasmodium falciparum. Immunization of mice withEscherichia coli-produced recombinant protein of the SERA N-terminal domain (SE47′) induced an antiserum that was inhibitory to parasite growth in vitro. Affinity-purified mouse antibodies specific to the recombinant protein inhibited parasite growth between the schizont and ring stages but not between the ring and schizont stages. When Percoll-purified schizonts were cultured with the affinity-purified SE47′-specific antibodies, schizonts and merozoites were agglutinated. Indirect-immunofluorescence assays with unfixed parasite cells showed that SE47′-specific immunoglobulin G (IgG) bound to SERA molecules on rupturing schizonts and merozoites but the IgG did not react with the schizont-infected erythrocytes (RBC). Furthermore, double-fluorescence staining against SE47′-specific IgG and anti-human RBC membrane IgG showed that the RBC membrane disappeared from SE47′-specific-IgG-bound schizonts after cultivation. These observations suggest that the SE47′-specific antibodies inhibit parasite growth by cross-linking SERA molecules that are associated with merozoites in rupturing schizonts with partly broken RBC and parasitophorous vacuole membranes, blocking merozoite release.

scholarly journals Antimalarial Activity of 77 Phospholipid Polar Head Analogs: Close Correlation Between Inhibition of Phospholipid Metabolism and In Vitro Plasmodium Falciparum Growth

Blood ◽  
1998 ◽  
Vol 91 (4) ◽  
pp. 1426-1437 ◽  
Author(s):  
Marie L. Ancelin ◽  
Michèle Calas ◽  
Jacques Bompart ◽  
Gérard Cordina ◽  
Dominique Martin ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
De Novo ◽  
Antimalarial Activity ◽  
Close Correlation ◽  
Phospholipid Metabolism ◽  
Parasite Growth ◽  
Human Lymphoblastoid Cell ◽  
Ofplasmodium Falciparum ◽  
Contrast Measurement

Abstract Seventy-seven potential analogs of phospholipid polar heads, choline and ethanolamine, were evaluated in vitro as inhibitors ofPlasmodium falciparum growth. Their IC50 ranged from 10−3 to 10−7 mol/L. Ten compounds showed similar antimalarial activity when tested against three different parasite strains (2 chloroquine-sensitive strains and 1 chloroquine-resistant strain). Compounds showing marked antimalarial activity were assayed for their effects on phospholipid metabolism. The most active compounds (IC50 of 1 to 0.03 μmol/L) were inhibitors of de novo phosphatidylcholine (PC) biosynthesis from choline. For a series of 50 compounds, there was a close correlation between impairment of phospholipid biosynthesis and inhibition of in vitro malaria parasite growth. High choline concentrations caused a marked specific shift in the curves for PC biosynthesis inhibition. Concentrations inhibiting 50% PC metabolism from choline were in close agreement with the Ki of these compounds for the choline transporter inPlasmodium knowlesi-infected erythrocytes. By contrast, measurement of the effects of 12 of these compounds on rapidly dividing lymphoblastoid cells showed a total absence of correlation between parasite growth inhibition and human lymphoblastoid cell growth inhibition. Specific antimalarial effects of choline or ethanolamine analogs are thus likely mediated by their alteration of phospholipid metabolism. This indicates that de novo PC biosynthesis from choline is a very realistic target for new malaria chemotherapy, even against pharmacoresistant strains.

Use of Protein a Conjugated to Peroxidase to Localize Immunoglobulin G in SSPE Ferret Brain

1982 ◽  
Vol 40 ◽  
pp. 350-351
Author(s):  
Hannah R. Brown ◽  
Anthony F. Nostro ◽  
Halldor Thormar
Keyword(s):  
Immunoglobulin G ◽  
Human Disease ◽  
Measles Virus ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Inflammatory Lesions ◽  
Sspe Virus ◽  
Specific Immunoglobulin ◽  
Antibody Titers ◽  
The Brain

Subacute sclerosing panencephalitis (SSPE) is a slowly progressing disease of the CNS in children which is caused by measles virus. Ferrets immunized with measles virus prior to inoculation with the cell associated, syncytiogenic D.R. strain of SSPE virus exhibit characteristics very similar to the human disease. Measles virus nucleocapsids are present, high measles antibody titers are found in the sera and inflammatory lesions are prominent in the brains. Measles virus specific immunoglobulin G (IgG) is present in the brain,and IgG/ albumin ratios indicate that the antibodies are synthesized within the CNS.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

Prevalence and Induction of Circulating Antibodies against Recombinant Staphylokinase

1994 ◽  
Vol 71 (01) ◽  
pp. 129-133 ◽  
Author(s):  
P J Declerck ◽  
S Vanderschueren ◽  
J Billiet ◽  
H Moreau ◽  
D Collen
Keyword(s):  
Intravenous Administration ◽  
Human Subjects ◽  
Microtiter Plates ◽  
Staphylococcus Aureus Bacteremia ◽  
Alternative Agent ◽  
Antibody Titers ◽  
Potential Alternative ◽  
Circulating Antibodies ◽  
Low Levels ◽  
Antibody Levels

SummaryStreptokinase (SK) is a routinely used thrombolytic agent but it is immunogenic and allergenic; staphylokinase (STA) is a potential alternative agent which is under early clinical evaluation. The comparative prevalence of antibodies against recombinant STA (STAR) and against SK was studied in healthy subjects and their induction with intravenous administration in small groups of patients.Enzyme-linked immunosorbent assays, using microtiter plates coated with STAR or SK and calibration with affinospecific human antibodies, revealed 2.1 to 65 μg/ml (median 11 μg/ml) anti-STAR antibodies and 0.9 to 370 μg/ml (median 18 μg/ml) anti-SK antibodies (p <0.001 vs anti-STAR antibodies) in plasma from 100 blood donors, with corresponding values of 0.6 to 100 μg/ml (median 7.1 μg/ml) and 0.4 to 120 μg/ml (median 7.3 μg/ml), respectively, in 104 patients with angina pectoris. Three out of 17 patients with Staphylococcus aureus bacteremia had significantly increased anti-STAR antibody levels (150, 75 and 75 μg/ml), and STAR neutralizing activities (2.2, 3.6 and 4.1 μg STAR neutralized per ml plasma, respectively). In 6 patients with acute myocardial infarction, given 10 mg STAR intravenously over 30 min, median anti-STAR antibody levels were 3.5 μg/ml at baseline, 2.9 μg/ml at 6 to 8 days and 1.2 μg/ml at 2 to 9 weeks, with median corresponding titers of STAR neutralizing activity at 2 to 9 weeks of 42 μg/ml plasma. Conversely, in 5 patients treated with 1,500,000 units SK over 60 min, median anti-SK antibodies increased from 2.9 μg/ml at baseline to 360 μg/ml at 5 to 10 days, with corresponding median SK neutralizing activities of 13 μg/ml. Antibodies against STAR did not cross-react with SK and vice versa.Plasma from human subjects contains low levels of circulating antibodies against recombinant staphylokinase, and intravenous administration of this compound boosts antibody titers. These antibodies do however not cross-react with streptokinase, whereby the use of these two immunogenic thrombolytic agents would not be mutually exclusive.

The Relationship between Plasma Microparticles, Protein S and Anticardiolipin Antibodies in Patients with Human Immunodeficiency Virus Infection

1996 ◽  
Vol 76 (01) ◽  
pp. 038-045 ◽  
Author(s):  
Jean-Christophe Gris ◽  
Pierre Toulon ◽  
Sophie Brun ◽  
Claude Maugard ◽  
Christian Sarlat ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Anticardiolipin Antibody ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Protein S Deficiency ◽  
Free Protein ◽  
Precipitation Technique ◽  
S Deficiency ◽  
Immunodeficiency Virus ◽  
Antibody Titers

SummaryThe high prevalence of free protein S deficiency in human immunodeficiency virus (HlV)-infected patients is poorly understood. We studied 38 HIV seropositive patients. Free protein S antigen values assayed using the polyethylene-glycol precipitation technique (PEG-fS) were statistically lower in patients than in controls. These values using a specific monoclonal antibody-based ELISA (MoAb-fS) and the values of protein S activity (S-act) were not statistically different between patients and controls. C4b-binding protein values were not different from control values. In patients, PEG-fS values were lower than MoAb-fS values. Ten patients had a PEG-fS deficiency, 4 patients had a MoAb-fS deficiency and 8 had a S-act deficiency. Protein S activity and MoAb-fS were lower in clinical groups with poor prognosis and in patients with AIDS but PEG-fS was not. A trend for reduced S-act/MoAb-fS ratios was observed in patients. PEG-fS was negatively correlated with anticardiolipin antibody titers whereas MoAb-fS was not. The plasma of PEG-fS deficient HIV-patients contained high amounts of flow cytometry detectable microparticles which were depleted from plasma by PEG precipitation. The microparticles were partly CD42b and CD4 positive but CD8 negative. These microparticles were labelled by an anti free protein S monoclonal antibody. The observed differences between MoAb-fS and PEG-fS values were correlated with the amount of detectable plasma microparticles, just like the differences between MoAb-fS and S-act. Plasma microparticles correlated with anticardiolipin antibody titers.In summary, free protein S antigen in HIV infected patients is underestimated when the PEG precipitation technique is used due to the presence of elevated levels of microparticles that bind protein S. The activity of free protein S is also impaired by high levels of microparticles. The prevalence of free protein S deficiency in HIV positive patients is lower than previously published (4/38, -10%) and is correlated with poor prognosis. By implication, use of a PEG precipitation technique might give artefactually low free protein S antigen values in other patient groups if high numbers of microparticles are present. In HIV patients, high titers of anticardiolipin antibodies are associated with high concentrations of cell-derived plasma microparticles.

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