Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the expression in Escherichia coli, isolation by immunological screening and complete nucleotide sequence of a cDNA clone from the malaria parasite Plasmodium falciparum. The deduced amino acid sequence contains separate blocks of repetitive hexapeptide and pentapeptide sequences and we have confirmed that these represent epitopes by reaction of the corresponding synthetic peptides with human antibodies. As the predicted size is Mr 21,000 and the overall composition is 30% His and 29% Ala, the polypeptide has been termed the small histidine-alanine rich protein (SHARP). This polypeptide is highly polymorphic in different P. falciparum isolates and cross reacts immunologically with a distinct gene product of P. falciparum. Although it is related to the Histidine Rich Protein (HRP) of P. lophurae by virtue of its high His content, it shows no obvious sequence relationship to the HRP outside the repeats.
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PMID:Sequence of a cDNA encoding a small polymorphic histidine- and alanine-rich protein from Plasmodium falciparum. 241 25

This report describes the isolation of a viruslike particle from in vitro cultures of the human malaria parasite P. falciparum. Electronmicroscopic observations suggest that the particles are liberated into the culture medium by budding from the erythrocyte membrane. The density of the free particles is 1.16, they contain nucleic acid and two distinct molecular species of the knob-associated Histidine-rich protein. Proteins of the particles are recognized by sera from malaria patients. The previously described knobs may correspond to viral coats inserted in the membrane.
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PMID:Viruslike particles containing knob-associated histidine-rich protein are secreted into the culture medium of Plasmodium falciparum in vitro cultures. 327 53

We have constructed a second generation malaria transmission-blocking vaccine candidate based on Pfs25, the predominate surface protein of Plasmodium falciparum zygotes, to overcome potential production problems with the original construct. Four modifications were made: (1) addition of the last cysteine residue of the fourth epidermal growth factor like-domain of Pfs25; (2) mutagenesis of asparagine-linked glycosylation sites with glutamine rather than alanine; (3) addition of a six histidine tag at the carboxy-terminus for highly efficient purification of recombinant protein on nickel-NTA agarose; and (4) fermentation that combines continuous glucose fed-batch methodology with pH-controlled glucose addition and a terminal ethanol feed. The resulting product, TBV25H (Transmission-Blocking Vaccine based on Pfs25 with a Histidine tag), appears to be a more potent antigen and immunogen than the original construct, and the fermentation and post-fermentation processing methodology easily lend themselves to technology transfer to the ultimate users, newly industrialized countries.
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PMID:Production, purification and immunogenicity of a malaria transmission-blocking vaccine candidate: TBV25H expressed in yeast and purified using nickel-NTA agarose. 776 8

Intraerythrocytic malaria parasites ingest the cytosol of their host cell and digest it inside their acid food vacuoles. Acidified (pH 4-5.5, 37 degrees C) human red blood cell lysates were used to simulate this process, measuring the denaturation of hemoglobin (Hb) and the release of iron, in the absence or presence of exogenous protease. Spontaneous Hb denaturation and appearance of non-heme iron were observed upon lysate acidification, its rate decreasing with increasing pH, and increasing in presence of protease. Although the pH- and proteolysis-dependent release of iron paralleled Hb denaturation, released iron accounted for only a few percent of degraded Hb. Superoxide dismutase, catalase, and various scavengers of oxidative radicals had no effect on either process, consistent with the involvement of Fe(IV) intermediates in iron release from heme. Histidine and imidazole inhibited iron release, probably by binding directly to heme. Ascorbate enhanced iron release considerably but marginally enhanced the denaturation of Hb, suggesting that redox cycling of lysate free iron accelerated further release from heme. These processes could account for the endogenous supply of iron to the malarial parasite.
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PMID:Hemoglobin denaturation and iron release in acidified red blood cell lysate--a possible source of iron for intraerythrocytic malaria parasites. 822 82

Histidine-rich proteins have been associated with Plasmodium falciparum infected red blood cells (RBC) cytoadherence, and RBC rosetting; these phenomena may cause clogging of the post-capillary venules, this being one of the main causes of severe cerebral malaria. They may also participate in parasite mature stages' evasion of the immune system and their subsequent destruction in the spleen. Non-overlapping synthetic peptides, corresponding to entire amino acid sequences reported for the KAHRP-I, HRP-II and HRP-III proteins, were used in RBC binding assays. Peptides with high and low binding activity were recognized. The KAHRP-I protein shows 3 peptides with high binding affinity to RBCs, two of them variable (peptide 6783, sequence 321QNYVHPWSGYSAPYGVPHGA(340) and peptide 6789, sequence 441KKREKSIMEKNHAAKKLTKK(460)) and the other conserved (peptide 6786, sequence 381KSKKHKDHDGEKKKSKKHKD(400)) having affinity constant of around 190 nM and 1000 binding sites per cell. Interestingly, this peptide shares aminoacid sequences with one reported as being recognized by malaria exposed human antibodies. The HRP-I protein also presents one conserved peptide (peptide 6800, sequence 24NNSAFNNNLCSKNAKGLNLN(43)) with high affinity, located in the amino terminal region of the native protein, having 210 nM affinity constant and 6000 receptor sites. The HRP-III protein only contains peptides with low binding activity. Treatment of red blood cells with neuraminidase reduces the binding of the conserved high binding 6786 and 6800 peptides. Anti-glycophorins A, B and C antibodies inhibit the binding of the conserved high binding 6786 and 6800 peptides. Furthermore, the specific determination of glycoproteins by chemioluminescenoe, in SDS/PAGE western blot, suggests that these glycophorins could be the receptor for these high binding peptides. High binding peptides' critical amino acids, involved in RBC binding were determined by means of competition binding assays.
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PMID:Plasmodium falciparum: red blood cell binding studies of peptides derived from histidine-rich KAHRP-I, HRP-II and HRP-III proteins. 1083 19

Blood samples collected from 34 patients with severe malaria who were involved in antimalarial treatment studies were tested with rapid dipstick assay (Rapid Test Malaria, RTM from Quorum Diagnostics Inc., Vancouver, BC, Canada), based on the detection of Histidine Rich Protein (HRP-2) of Plasmodium falciparum. This was compared with the conventional Giemsa stained thin and thick blood smears. The study was done from March 1998 to May 1998, at the Basic Research Laboratory of the Faculty of Medicine, Addis Ababa University. Comparable number of patients (n = 32) with various diagnosis other than falciparum malaria were used as controls. The rapid dip-stick assay was positive in 31 among 34 of the severe malaria cases with sensitivity of 91.2%, specificity of 93.7%, positive predictive value (PPV) of 93.9% and negative predictive value (NPV) of 90.9%. The three cases missed by the RTM, had parasitemia of 66,000, 44,000, and 40,000/microL of blood which might be due to genetic heterogeneity of the HPR-2 expression. Among the controls, there were 2 false positive cases which may be as a result of persistent HPR-2 antigen after the clearance of peripheral parasitemia. The dip-stick method is a very quick, sensitive and specific diagnostic tool with limits of detection comparable or better than those provided by the light microscopy. The simplicity of the technique makes this method more applicable in the resource deprived laboratories of developing countries provided the kit is affordable for large scale use.
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PMID:Rapid diagnosis of severe malaria based on the detection of Pf-Hrp-2 antigen. 1195 14

Malaria is the most important parasitic disease worldwide. With the advent of multidrug-resistant strains, it is highly important that the disease be diagnosed both early and accurately. For the diagnosis of malaria parasites, the thick blood film approach remains the gold standard. However, the use of that standard requires a microscope, stains, and a trained microscopist to interpret the films. The author describes the microscopical detection of the malaria parasite through the use of fluorochrome as well as the development of antigen detection tests to improve the laboratory diagnosis of malaria. Histidine-rich protein II (HRPII) is expressed by the asexual stages of Plasmodium falciparum. The detection of HRPII antigen appears to be a useful alternative diagnostic technique when microscopes are unavailable. However, a negative test result may indicate the presence of non-P falciparum malaria or that it is too early in the course of infection to detect parasites. One advantage of a parasite lactate dehydrogenase (pLDH) detection system is its ability to detect all 4 species of malaria and to diagnose both P. falciparum and P. vivax infections.
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PMID:Latest developments in the laboratory diagnosis of malaria. 1229 40

Major blood stage antimalarial drugs like chloroquine and artemisinin target the heme detoxification process of the malaria parasite. Hemozoin formation reactions in vitro using the Plasmodium falciparum histidine-rich protein-2 (Pfhrp-2), lipids, and auto-catalysis are slow and could not explain the speed of detoxification needed for parasite survival. Here, we show that malarial hemozoin formation is a coordinated two component process involving both lipids and histidine-rich proteins. Hemozoin formation efficiency in vitro is 1-2% with Pfhrp-2 and 0.25-0.5% with lipids. We added lipids after 9h in a 12h Pfhrp-2 mediated reaction that resulted in sixfold increase in hemozoin formation. However, a lipid mediated reaction in which Pfhrp-2 was added after 9h produced only twofold increase in hemozoin production compared to the reaction with Pfhrp-2 alone. Synthetic peptides corresponding to the Pfhrp-2 heme binding sequences, based on repeats of AHHAAD, neither alone nor in combination with lipids were able to generate hemozoin in vitro. These results indicate that hemozoin formation in malaria parasite involves both the lipids and the scaffolding proteins. Histidine-rich proteins might facilitate hemozoin formation by binding with a large number of heme molecules, and facilitating the dimer formation involving iron-carboxylate bond between two heme molecules, and lipids may then subsequently assist the mechanism of long chain formation, held together by hydrogen bonds or through extensive networking of hydrogen bonds.
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PMID:Hemozoin formation in malaria: a two-step process involving histidine-rich proteins and lipids. 1292 80

Inflammatory responses of human peripheral blood monocytes to the Gram-negative endotoxin lipopolysaccharide (LPS) are enhanced by structurally diverse substances, such as anionic polysaccharides or cationic polypeptides. Only a few substances are known to effectively blunt LPS-induced monocyte activation. We now show that synthetic poly-L-histidine (Hn) binds to LPS and abrogates the release of the proinflammatory cytokine interleukin-8 (IL-8) in LPS-stimulated human whole blood. LPS-induced stimulation of monocytes was strictly pH-dependent with only minor amounts of IL-8 secreted in acidic blood. Maximum levels of IL-8 secretion occurred at a strongly basic pH. Hn inhibition of the release of IL-8 from LPS-stimulated monocytes was observed under acidic, neutral and physiological conditions. With increasing alkalosis, the effectiveness of Hn was gradually lost, suggesting that protonated, but not deprotonated, Hn was effective in inhibiting LPS-induced monocyte responses. Histidine-rich protein 2 from the malaria parasite, Plasmodium falciparum, inhibited the ability of LPS to evoke an inflammatory response in CD14-transfected THP-1 cells. Further, a short synthetic peptide derived from human histidine- and proline-rich glycoprotein also exhibited LPS-inhibitory effects in CD14 transfectants. Taken together, these observations demonstrate the capacity of histidine-rich peptides, irrespective of their origin, to neutralize LPS-induced proinflammatory host responses.
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PMID:Endotoxin-neutralizing effects of histidine-rich peptides. 1455 May 61

Severe pulmonary involvement in malaria has been frequently reported in cases of Plasmodium falciparum infection, but rarely in vivax malaria. Among the 11 previous cases of vivax-related severe respiratory involvement described in the literature, all except one developed it after the beginning of anti-malarial treatment; these appear to correspond to an exacerbation of the inflammatory response. We report the case of a 43-year-old Brazilian woman living in a malaria-endemic area, who presented acute respiratory distress syndrome (ARDS) caused by P. vivax before starting anti-malarial treatment. The diagnosis was made based on microscopic methods. A negative rapid immunochromatographic assay, based on the detection of Histidine Rich Protein-2 (HRP-2) of P. falciparum, indicated that falciparum malaria was unlikely. After specific anti-plasmodial therapy and intensive supportive care, the patient was discharged from the hospital. We conclude that vivax malaria-associated ARDS can develop before anti-malarial therapy.
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PMID:Acute respiratory distress syndrome due to vivax malaria: case report and literature review. 1641 Aug 95


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