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- Chen, Q, et al.
(author)
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Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum
- 1998
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 187:1, s. 15-23
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Journal article (peer-reviewed)abstract
- Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum–infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1–glutathione S transferase; Duffy binding-like-1–GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate–like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.
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| 4. |
- Cruz, Silian, et al.
(author)
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Mouse monoclonal antibodies against outer membrane proteins of a vaccine strain of Neisseria meningitidis B : 4:P1.15
- 1998
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In: Minerva Biotecnologica. - 1120-4826. ; 10:2, s. 65-70
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Journal article (peer-reviewed)abstract
- Background. Neisseria meningitidis (Nm) is a Gram negative diplococcus causing bacterial meningitis and fulminant septicemia. In order to allow efficient characterization of infecting strains, antibody reagents for use as analytical tools have proven to be invaluable tools. Similarly, antibodies against relevant bacterial antigens may guide in the selection of components to be included in developing vaccine strategies. Methods. We have thus developed mouse monoclonal antibodies specific for class 1, 3 and 5 antigens expressed by the B:4:P1.15 isolate CU385/83, also being used in a recently developed protective vaccine. In particular, two antibodies CB-Nm.1 and CB- Nm.2 recognize epitopes partly overlapping the subserotype (class 1 antigens) and serotype (class 3 antigen) specificities detected by the previously defined antibodies C6 and 15-1-P4 respectively, were evaluated. Results. As judged by strain recognition, the absolute requirement for binding differs between both the class 1-specific and class 3 specific antibodies suggesting the importance of using multiple antibodies when evaluating subserotype/serotype characteristics of clinical isolates of Nm by serological methods. Conclusion. Furthermore, the development of antibodies crossreactive with subserotype/serotype antigens may partly explain the ability of outer membrane protein vaccine to induce protective activity against strains considered as carrying different class 1 and 3 antigens as determined by available (sub)serotyping reagents.
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| 8. |
- Fernandez, V, et al.
(author)
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Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses
- 1999
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 190:10, s. 1393-1403
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Journal article (peer-reviewed)abstract
- Disease severity in Plasmodium falciparum infections is a direct consequence of the parasite's efficient evasion of the defense mechanisms of the human host. To date, one parasite-derived molecule, the antigenically variant adhesin P. falciparum erythrocyte membrane protein 1 (PfEMP1), is known to be transported to the infected erythrocyte (pRBC) surface, where it mediates binding to different host receptors. Here we report that multiple additional proteins are expressed by the parasite at the pRBC surface, including a large cluster of clonally variant antigens of 30–45 kD. We have found these antigens to be identical to the rifins, predicted polypeptides encoded by the rif multigene family. These parasite products, formerly called rosettins after their identification in rosetting parasites, are prominently expressed by fresh isolates of P. falciparum. Rifins are immunogenic in natural infections and strain-specifically recognized by human immune sera in immunoprecipitation of surface-labeled pRBC extracts. Furthermore, human immune sera agglutinate pRBCs digested with trypsin at conditions such that radioiodinated PfEMP1 polypeptides are not detected but rifins are detected, suggesting the presence of epitopes in rifins targeted by agglutinating antibodies. When analyzed by two-dimensional electrophoresis, the rifins resolved into several isoforms in the pI range of 5.5–6.5, indicating molecular microheterogeneity, an additional potential novel source of antigenic diversity in P. falciparum. Prominent polypeptides of 20, 22, 76–80, 140, and 170 kD were also detected on the surfaces of pRBCs bearing in vitro–propagated or field-isolated parasites. In this report, we describe the rifins, the second family of clonally variant antigens known to be displayed by P. falciparum on the surface of the infected erythrocyte.
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| 11. |
- Perlmann, P, et al.
(author)
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Immunoglobulin E, a pathogenic factor in Plasmodium falciparum malaria
- 1997
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In: Infection and immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 65:1, s. 116-121
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Journal article (peer-reviewed)abstract
- Most children and adults living in areas where the endemicity of Plasmodium falciparum malaria is high have significantly elevated levels of both total immunoglobulin E (IgE) and IgE antimalarial antibodies in blood. This elevation is highest in patients with cerebral malaria, suggesting a pathogenic role for this immunoglobulin isotype. In this study, we show that IgE elevation may also be seen in severe malaria without cerebral involvement and parallels an elevation of tumor necrosis factor alpha (TNF). IgE-containing serum from malaria immune donors was added to tissue culture plates coated with rabbit anti-human IgE antibodies or with P. falciparum antigen. IgE-anti-IgE complexes as well as antigen-binding IgE antibodies induced TNF release from peripheral blood mononuclear cells (PBMC). Nonmalaria control sera with no IgE elevation induced significantly less of this cytokine, and the TNF-inducing capacity of malaria sera was also strongly reduced by passing them over anti-IgE Sepharose columns. The cells giving rise to TNF were adherent PBMC. The release of this cytokine probably reflects cross-linking of their low-affinity receptors for IgE (CD23) by IgE-containing immune complexes known to give rise to monocyte activation via the NO transduction pathway. In line with this, adherent monocytic cells exposed to IgE complexes displayed increased expression of CD23. As the malaria sera contained IgG anti-IgE antibodies, such complexes probably also play a role in the induction of TNF in vivo. Overproduction of TNF is considered a major pathogenic mechanism responsible for fever and tissue lesions in P. falciparum malaria. This overproduction is generally assumed to reflect a direct stimulation of effector cells by certain parasite-derived toxins. Our results suggest that IgE elevation constitutes yet another important mechanism involved in excessive TNF induction in this disease.
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| 12. |
- Rakov, V. A., et al.
(author)
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New insights into lightning processes gained from triggered-lightning experiments in Florida and Alabama
- 1998
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 103:D12, s. 14117-14130
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Journal article (peer-reviewed)abstract
- Analyses of electric and magnetic fields measured at distances from tens to hundreds of meters from the ground strike point of triggered lightning at Camp Blanding, Florida, and at 10 and 20 m at Fort McClellan, Alabama, in conjunction with currents measured at the lightning channel base and with optical observations, allow us to make new inferences on several aspects of the lightning discharge and additionally to verify the recently published “two-wave†mechanism of the lightning M component. At very close ranges (a few tens of meters or less) the time rate of change of the final portion of the dart leader electric field can be comparable to that of the return stroke. The variation of the close dart leader electric field change with distance is somewhat slower than the inverse proportionality predicted by the uniformly charged leader model, perhaps because of a decrease of leader charge density with decreasing height associated with an incomplete development of the corona sheath at the bottom of the channel. There is a positive linear correlation between the leader electric field change at close range and the succeeding return stroke current peak at the channel base. The formation of each step of a dart-stepped leader is associated with a charge of a few millicoulombs and a current of a few kiloamperes. In an altitude-triggered lightning the downward negative leader of the bidirectional leader system and the resulting return stroke serve to provide a relatively low-impedance connection between the upward moving positive leader tip and the ground, the processes that follow likely being similar to those in classical triggered lightning. Lightning appears to be able to reduce, via breakdown processes in the soil and on the ground surface, the grounding impedance which it initially encounters at the strike point, so at the time of channel-base current peak the reduced grounding impedance is always much lower than the equivalent impedance of the channel. At close ranges the measured M-component magnetic fields have waveshapes that are similar to those of the channel-base currents, whereas the measured M-component electric fields have waveforms that appear to be the time derivatives of the channel-base current waveforms, in further confirmation of the “two-wave†M-component mechanism.
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| 15. |
- Wahlgren, M, et al.
(author)
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Adhesion of Plasmodium falciparum-infected erythrocytes to human cells and secretion of cytokines (IL-1-beta, IL-1RA, IL-6, IL-8, IL-10, TGF beta, TNF alpha, G-CSF, GM-CSF
- 1995
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In: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 42:6, s. 626-636
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Journal article (peer-reviewed)
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