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A Szarfman

Publications and source records attributed to A Szarfman.

At least 19 recordsLinked to original sources
PubMed1996

Cross-reactive epitope among proteins in Plasmodium falciparum Maurer's clefts and primate leukocytes and platelets.

Erythrocytes infected with malaria parasites often contain membranous vesicles that are presumed to facilitate macromolecule traffic between the parasite and erythrocyte membranes. One such vesicle network, called Maurer's clefts, is expressed in Plasmodium falciparum-infected erythrocytes and contains a 50-kD polypeptide. Using a monoclonal antibody reactive with this polypeptide, we show that hepatic stages of P. falciparum express an epitope common to this blood-stage antigen. In addition, this epitope is cross-reactive with antigens expressed by primate leukocytes and platelets. Such epitopes may induce autoantibodies commonly seen in patients with malaria.

Animals↗
PubMed1992

Characterization of Plasmodium falciparum sporozoite surface protein 2.

Immunization of mice with Plasmodium yoelii sporozoite surface protein 2 (PySSP2) and circumsporozoite protein protects completely against P. yoelii. The amino acid sequence of PySSP2 suggested that the thrombospondin-related anonymous protein (TRAP) [Robson, K. J. H., Hall, J. R. S., Jennings, M. W., Harris, T. J. R., Marsh, K., Newbold, C. I., Tate, V. E. & Weatherall, D. J. (1988) Nature (London) 335, 79-82] is the Plasmodium falciparum homolog of PySSP2. We report data confirming that TRAP is P. falciparum SSP2 (PfSSP2). Murine antibodies against recombinant PfSSP2 identify a 90-kDa protein in extracts of P. falciparum sporozoites, recognize sporozoites and infected hepatocytes by immunofluorescence, localize PfSSP2 to the sporozoite micronemes by immunoelectron microscopy and to the surface membrane by live immunofluorescence, and inhibit sporozoite invasion and development in hepatocytes in vitro. Human volunteers immunized with irradiated sporozoites and protected against malaria develop antibody and proliferative T-cell responses to PfSSP2, suggesting that, like PySSP2, PfSSP2 is a target of protective immunity, and supporting inclusion of PfSSP2 in a multicomponent malaria vaccine.

Amino Acid Sequence↗
PubMed1990

Effect of malaria chemoprophylaxis on the development of antibodies to Plasmodium falciparum in expatriates living in west Africa.

We studied the relationship between exposure to malaria, the use of long-term chemoprophylaxis with chloroquine, and the prevalence of sporozoite antibodies in 446 expatriates who had lived in 7 West African countries for 6 months-41 years. Filter paper blood samples from 12% of the subjects had antibodies to the repeat region of the Plasmodium falciparum circumsporozoite protein, with a positive correlation between enzyme-linked immunosorbent assay (ELISA) absorbance and years of exposure (r = 0.32, P = less than 0.01). Development of sporozoite antibodies did not correlate with reported use of chloroquine. Ten samples from expatriates with the highest ELISA titers and 10 samples from West African nationals, which were matched for ELISA titer and duration of exposure, were characterized more fully. All 20 samples reacted strongly with sporozoites by immunofluorescence. The 10 samples from nationals reacted strongly with liver-stage antigens by immunofluorescence and with blood-stage antigens by immunofluorescence and immunoblotting. In contrast, the 10 samples from expatriates were negative or only weakly positive in the liver- and blood-stage assays. These results imply that sporozoite antibodies are generally not cross-reactive with blood-stage antigens, and suggest that protective immunity to malaria does not develop during long-term malaria chemoprophylaxis against the erythrocytic stage.

Adolescent↗
PubMed1990

T lymphocytes from mice immunized with irradiated sporozoites eliminate malaria from hepatocytes.

When mice are immunized with radiation-attenuated sporozoites they are solidly protected against sporozoite challenge by an immune response that has been shown to require CD8+ lymphocytes in several strains of mice. The target of this CD8+ T-cell-dependent immunity has not been established. Immune BALB/c mice were shown to develop malaria-specific, CD8+ T-cell-dependent inflammatory infiltrates in their livers after challenge with Plasmodium berghei sporozoites. Spleen cells from immune BALB/c and C57BL/6 mice eliminated hepatocytes infected with the liver stage of P. berghei in vitro. The activity against infected hepatocytes is not inhibited by antibodies to interferon-gamma and is not present in culture supernatants. It is genetically restricted, an indication that malaria antigens on the hepatocyte surface are recognized by immune T-effector cells. Further subunit pre-erythrocytic stage malaria vaccine development will require identification of the antigens recognized by these T cells and a method of immunization that induces such immunity.

Animals↗
PubMed1989

Sporozoite vaccine induces genetically restricted T cell elimination of malaria from hepatocytes.

The target of the CD8+ T cell-dependent immunity that protects mice immunized with irradiation-attenuated malaria sporozoites has not been established. Immune BALB/c mice were shown to develop malaria-specific, CD8+ T cell-dependent inflammatory infiltrates in their livers after challenge with Plasmodium berghei sporozoites. Spleen cells from immune BALB/c and C57BL/6 mice eliminated hepatocytes infected with the liver stage of P. berghei in vitro. The activity against infected hepatocytes is not inhibited by antibodies to interferon-gamma and is not present in culture supernatants. It is genetically restricted, an indication that malaria antigens on the hepatocyte surface are recognized by immune T effector cells. Subunit vaccine development will require identification of the antigens recognized by these T cells and a method of immunization that induces such immunity.

Animals↗
PubMed1988

Allelic forms of gp195, a major blood-stage antigen of Plasmodium falciparum, are expressed in liver stages.

Mature exoerythrocytic (EE) forms of two cloned lines (3D7 and HB3) of Plasmodium falciparum were obtained in the livers of splenectomized chimpanzees. Sectioned preparations were examined by immunofluorescence (IFA) using mAbs that distinguished allelic variants of the blood-form antigen gp195 and mAbs that recognized multiple conserved epitopes of gp195. EE forms and blood schizonts exhibited identical IFA reactions for each respective clone, showing that the antigen was expressed identically in liver and blood-stage parasites. A third chimpanzee was infected with sporozoites derived from a mixture of 3D7 and HB3 gametocytes that had undergone cross-fertilization in the mosquitoes. IFAs on the EE forms in this animal showed that segregation of each gp195 allele had occurred earlier in the life cycle, providing evidence that the parasite is haploid for the whole of its mammalian development.

Alleles↗
PubMed1988

Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages.

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.

Animals↗
PubMed1987

Circulating antibodies to mouse laminin in Chagas disease, American cutaneous leishmaniasis, and normal individuals recognize terminal galactosyl(alpha 1-3)-galactose epitopes.

Sera from patients with American cutaneous leishmaniasis and Chagas disease and from monkeys infected with either Trypanosoma cruzi or Trypanosoma rhodesiense show, in RIAs, strong binding to mouse laminin. A distinct although weaker binding activity is also detected in normal human sera. The antibodies recognize a common carbohydrate epitope present on mouse laminin, which was assigned to a terminal galactosyl(alpha 1-3)-galactose group. Distinct crossreactions were observed with some other basement membrane proteins, rabbit glycosphingolipids, defucosylated human B blood group substance and components produced by some human tumor cells. Only little activity was, however, found on laminin obtained from human placenta. The data indicate that the antibodies arising in infectious diseases are stimulated by similar carbohydrate epitopes present on the surface of parasites. Tissue-specific occurrence of such epitopes may exist and explain the involvement of distinct tissues in autoimmune disorders.

Animals↗
PubMed1987

Genetic analysis of the human malaria parasite Plasmodium falciparum.

Malaria parasites are haploid for most of their life cycle, with zygote formation and meiosis occurring during the mosquito phase of development. The parasites can be analyzed genetically by transmitting mixtures of cloned parasites through mosquitoes to permit cross-fertilization of gametes to occur. A cross was made between two clones of Plasmodium falciparum differing in enzymes, drug sensitivity, antigens, and chromosome patterns. Parasites showing recombination between the parent clone markers were detected at a high frequency. Novel forms of certain chromosomes, detected by pulsed-field gradient gel electrophoresis, were produced readily, showing that extensive rearrangements occur in the parasite genome after cross-fertilization. Since patients are frequently infected with mixtures of genetically distinct parasites, mosquito transmission is likely to provide the principal mechanisms for generating parasites with novel genotypes.

Adenosine Deaminase↗
PubMed1986

Absence of left ventricular dysfunction during acute chagasic myocarditis in the rhesus monkey.

Recent studies suggest that intracellular Trypanosoma cruzi invasion with release of intracellular myocardial antigens during T. cruzi infection is crucial to the pathogenesis of chronic chagasic myocarditis. However, in areas endemic for Chagas' disease, the incidence of clinical acute chagasic myocarditis has been reported to be low among infected individuals, while the incidence of chronic chagasic myocarditis is relatively high. Thus, either acute chagasic myocarditis rarely complicates T. cruzi infection and is not important to the pathogenesis of chronic chagasic myocarditis, or acute chagasic myocarditis rarely impairs left ventricular function and therefore causes no symptoms. To investigate this question we innoculated T. cruzi from a human patient with Chagas' disease into the subconjuntivae of six rhesus monkeys (7.5 X 10(3) parasites each). Parasitemia was monitored and weekly two-dimensional echocardiograms (for determination of end-diastolic and fractional change in area, EDA and FCA) were obtained to quantify global left ventricular function for 10 weeks. Regional left ventricular function was assessed by visual analysis of two-dimensional echocardiograms. Extent of acute myocarditis was established at autopsy. All monkeys had the Romaña sign and detectable parasitemia in the second week. Parasitemia rose in all by the ninth week (mean = 1.8 X 10(5) parasites/ml); four monkeys lost weight (mean = -12%), three died, and three were killed. Two-dimensional echocardiographic EDA and FCA remained unchanged from control to the last study within 12 hr of death (EDA = 2.6 +/- 0.9 to 2.7 +/- 1.0 cm2, FCA = 80 +/- 6.8 to 74 +/- 7.6%, NS). Furthermore, regional left ventricular function remained unchanged throughout the period of study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Evaluation of a synthetic oligonucleotide probe for diagnosis of Plasmodium falciparum infections.

A radiolabeled synthetic oligonucleotide was evaluated as a diagnostic probe specific for Plasmodium falciparum using blood samples lysed directly on nitrocellulose filters. The probe technique successfully diagnosed malaria in experimentally infected chimpanzees that had 0.001% parasitemias (50 parasites/microliter) as determined by blood smears, and in 1 chimpanzee whose blood smear was negative, but whose blood was culture-positive for P. falciparum. In a double blind study of 50 patient samples from the Philippines, the probe results correlated well with blood smear results when the autoradiographs were read after 4-8 hr exposure. The results indicate that the oligonucleotide probe may be useful in the rapid and specific diagnosis of P. falciparum infection.

Animals↗
PubMed1982

Antibodies to laminin in Chagas' disease.

We have found that sera from humans with Chagas' disease and Rhesus monkeys infected with Trypanosoma cruzi contain IgM and IgG antibodies, which react with structures in a variety of connective tissues. These antibodies react with laminin but not with various other purified connective tissue components like collagen types I, III, IV, and V, fibronectin, heparan sulfate (BM-1) proteoglycan, or chondronectin. The tissue-reacting antibodies were isolated by absorption to a laminin-Sepharose column. The bound fraction contained all the tissue-reacting antibodies. These antibodies strongly stained trypomastigotes and amastigotes, but weakly stained epimastigotes. These studies show that sera from T. cruzi-infected primates contain antilaminin antibodies, which may be produced by those host in response to a laminin-like molecule present in the parasite.

Adolescent↗
PubMed1981

Autoantibodies and chronic Chagas's heart disease.

Serum samples from 150 individuals from an area in Brazil where Chagas's disease is endemic were examined for the presence of autoantibodies (EVI and PN). Patients were divided into four groups according to the diagnostic value and prognostic significance of electrocardiographic changes. Results confirmed a close relationship between the EVI and PN antibodies and chagasic infection but their presence does not appear to relate to the severity of Chagas's heart disease.

Adult↗