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)

Zymosan-activated and non-activated human polymorphonuclear neutrophils (PMN) were added to in-vitro cultures of the human malaria parasite Plasmodium falciparum in microtitre wells. Microscopic counting of parasites in Giemsa-stained smears showed that at a PMN:RBC ratio of 1:150, the same as occurs in human malaria, parasites in wells with zymosan-activated neutrophils were suppressed 65%. Determination of parasite nucleic acid synthesis by 3H-hypoxanthine incorporation showed that in wells with PMN:RBC ratio of 1:150 parasite viability was only 22% of control. Various oxygen scavengers were tested for ability to reverse the effects of activated neutrophils on parasite development. Superoxide dismutase (20 mg/ml) and catalase (50 mg/ml) had no effect; tryptophan protected the parasites to a moderate degree while histidine alleviated suppression of parasite development to the greatest extent. This suggests that singlet oxygen is the most effective neutrophil product in killing or suppressing the growth of parasites. We also observed that non-activated neutrophils were activated by parasites and/or their products resulting in killing of newly-released parasites.
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PMID:Evidence for a neutrophil-mediated protective response in malaria. 328 Nov 2

The current status of histidine-rich proteins in malaria parasites with regard to their genomic organization, protein structure and function is discussed, one of such protein present in an avian malaria parasite Plasmodium lophurae contains about 73% histidine and called as HRP (histidine-rich protein). Among human malaria parasites, in Plasmodium falciparum, only three such proteins have been described, namely knob protein also known as knob associated histidine-rich protein (KP or KAHRP), soluble histidine-alanine rich protein (soluble HARP or PfHRP II) and small histidine-alanine rich protein (SHARP) containing 8, 35 and 30% histidine contents respectively. With rapid emergence of powerful tools in molecular biology the genes of all these histidine-rich proteins have been cloned and sequenced within a short period of time. The genomic organizations of all these proteins are very much similar to each other, in each case the gene contains a signal peptide coding sequence (exon 1) followed by an intron. This intron is followed by the main coding region (exon 2) which has no further intervening sequences. In the main coding region of each gene, the histidine-rich sequences start after 25-30 amino acids from N-terminal end (75-90 nucleotides from 5' in exon 2). All the three histidine-rich proteins of P. falciparum share some homology with the HRP of P. lophurae; they all cross react with anti HRP and incorporate higher amount of exogenous histidine. The relationship between KP and HRP resides in the repeated polyhistidine sequences, (His) 6-9, from the core of the multiple tandem repeats of HRP, whereas, the peptide Ala-His-His is commonly shared by HRP and two other proteins of P. falciparum (soluble HARP and SHARP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Genomic organization, structure and possible function of histidine-rich proteins of malaria parasites. 328 10

Plasmodium falciparum-infected erythrocytes (IRBC) synthesize 3 histidine-rich proteins: HRP-I or the knob-associated HRP, HRP-II and HRP-III or SHARP. In order to distinguish these proteins immunochemically we prepared monoclonal antibodies which react with HRP-I, HRP-II and HRP-III, and rabbit antisera against synthetic peptides derived from the HRP-II and HRP-III sequences. A comparative analysis of diverse P. falciparum parasites was made using these antibodies and immunoprecipitation or Western blotting. HRP-I (Mr 80,000-115,000) was identified in all knob-positive P. falciparum parasites including isolates examined directly from Gambian patients. However, this protein was of lower abundance in these isolates and in 6 knob-positive, culture-adapted parasites compared to Aotus monkey-adapted parasites or culture-adapted parasites studied previously. HRP-II (Mr 60,000-105,000) was identified in all P. falciparum parasites regardless of knob-phenotype, and was recovered from culture supernatants as a secreted water-soluble protein. Within IRBC, HRP-II was found as a complex of several closely spaced bands. Cell surface radio-iodination of IRBC from several isolates and immunoprecipitation with a rabbit antiserum against the HRP-II repeat sequence identified HRP-II as a surface-exposed protein. Like HRP-I, the abundance of HRP-II was lower in the Gambian isolates than with Aotus monkey-adapted parasites studied earlier. Neither HRP-I nor HRP-II were identified in a knob-positive isolate of P. malariae collected from a Gambian patient. Analogues of these HRP were also absent from asexual parasites of diverse primate and murine malaria species screened with this panel of antibodies. HRP-III (Mr 40,000-55,000) was distinguished by its lower apparent size and by specific reaction with rabbit antibody against its 5-mer repeat sequence. HRP-III was of lowest abundance compared with the other two HRP. These antibody reagents and distinguishing properties should prove useful in studies on the separate functions of the 3 P. falciparum HRP.
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PMID:Comparative analysis of the Plasmodium falciparum histidine-rich proteins HRP-I, HRP-II and HRP-III in malaria parasites of diverse origin. 332 Aug 87

This report describes a Danish patient with severe Plasmodium falciparum infection and Pseudomonas aeruginosa septicaemia. The patient had been sailing along the coast of West Africa for ten years without taking any antimalaria prophylaxis and without any apparent previous history of malaria. He presented with severe form of malaria, progressing rapidly into coma and died within a short time. P. aeruginosa was isolated from his blood taken on the day of admission. His neutrophils were all occupied by P. falciparum. The unusual combination of severe falciparum malaria infection and P. aeruginosa septicaemia with extensive involvement of neutrophils lends further support for the role of phagocytic defence in malaria.
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PMID:Pseudomonas aeruginosa septicaemia in a patient with severe Plasmodium falciparum. 332 35

The human malaria parasite Plasmodium falciparum synthesizes several proteins that are unusually rich in histidine. We therefore screened histidine analogues for their capacity to inhibit in vitro parasite growth. Analogues were added to cultures of ring-stage parasites, and parasite morphological development was assessed by light microscopy after a 22-hr culture. Inhibition of morphological development was identified as the appearance of condensed or pycnotic parasites rather than mature trophozoites. Inhibition of parasite protein synthesis was assessed by radioactivity counting of [3H] isoleucine incorporated into acid-insoluble products and by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography of [3H]histidine-labeled malarial proteins. 2-F-L-Histidine and 2-I-D, L-histidine exerted the most pronounced inhibitory effects, the fluoro-analogue being the more effective of the two. At a 0.125 mM concentration, both compounds inhibited parasite growth and 2-F-L-histidine also inhibited protein synthesis. At a 1.0 mM concentration, 2-azido-L-histidine, alpha-methyl-L-histidine and WR 177589A also inhibited P. falciparum growth and protein synthesis. Twenty other histidine analogues, including 5-F-L-histidine and 5-I-L-histidine, showed little or no effect under these conditions. The inhibitory histidine analogues may be of interest for antimalarial chemotherapy if they should prove to have greater effect on P. falciparum protein synthesis than on host protein synthesis.
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PMID:Inhibitory effects of histidine analogues on growth and protein synthesis by Plasmodium falciparum in vitro. 351 22

Cultured Plasmodium falciparum was retarded in intraerythrocytic development by serum from malaria-immune adults, by human TB serum, and by rabbit tumor necrosis serum. Neither the potency nor efficacy of any of these sera was altered by a variety of antioxidants or oxygen-free radial scavengers, including ascorbate, alpha-tocopherol, BHT, cystine or cysteine, glutathione, histidine, phenylalanine, tryptophan, tyrosine, superoxide dismutase, catalase (or combination of the two enzymes), or by reducing the ambient O2 tension to 1%. It is thus unlikely that the antiparasitic activity of these inhibitory sera can be attributed to oxidative mechanisms.
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PMID:Antioxidants do not prevent the in vitro induction of Plasmodium falciparum crisis forms by human malaria-immune, TB or rabbit TNF serum. 352 84

Membranes of erythrocytes infected with the human malaria parasite Plasmodium falciparum develop protrusions called knobs. These structures are essential for the survival of the parasite in the host, and their induction requires the synthesis of the knob protein by the parasite. We describe the isolation of a cDNA clone encoding the amino-terminal half of the knob protein. A cDNA library was constructed from RNA prepared from ring stages of a P. falciparum isolate that has retained its ability to induce knobs (knob+ phenotype). A synthetic oligonucleotide probe encoding polyhistidine was used to isolate the cDNA clone, which encodes the amino-terminal half of a polypeptide with all the known attributes of the knob protein. The gene is not transcribed in variants that do not synthesize the knob protein and thereby cannot induce knobs (knob- phenotype). The apparent lack of transcription in knob- variants is due to different mechanisms: although the gene is present in one knob- isolate, it has been deleted in a cloned knob- variant. The primary structure of the polypeptide deduced from a partial sequence of the cDNA is distinctly different from other malarial histidine-rich polypeptides. The amino-terminal sequence shows the characteristic features of a signal peptide. This is followed by a histidine-rich domain and a subsequent region which contains one histidine. Peptide map analysis of the knob protein is consistent with the structural features deduced from the sequence analysis of the cDNA.
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PMID:Histidine-rich domain of the knob protein of the human malaria parasite Plasmodium falciparum. 353 26

A clinical case of Black Water Fever following Plasmodium falciparum infection is reported. The patient had no previous history of malaria and had not taken anti-malarials as prophylasis. He was free from G-6-PD deficiency and abnormal haemoglobins. He had acute intravascular haemolysis, haemoglobinurea and renal failure after the third dose of quinine infusion. His life was saved by peritoneal dialysis and Artemether injection. In in vitro test, his blood haemolysed suddenly in 36 hours when incubated with quinine (10 mg per lit) at 37 degrees C in test tube while control blood took over a week for natural slow haemolysis. Thus quinine plays an important part in the cause of Black Water Fever.
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PMID:A case of black water fever treated with peritoneal dialysis and artemether (quinghaosu derivative). 366 74

Rabbits were immunized with the histidine-rich protein (HRP) of the avian malaria parasite, Plasmodium lophurae. The anti-HRP immunoprecipitated the knob protein (KP) from extracts of the human parasite, Plasmodium falciparum. The anti-HRP did not react with any antigens of a laboratory-derived strain of P. falciparum (K-) that does not form knobs. Antisera raised against a membrane-enriched fraction of P. falciparum-infected erythrocytes as well as sera from humans exposed to P. falciparum infections immunoprecipitated HRP from P. lophurae extracts.
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PMID:Immunological cross-reactivity of the histidine-rich protein of Plasmodium lophurae and the knob protein of Plasmodium falciparum. 618 87

Fluorescence histochemical methods for the demonstration of specific residues in peptides and proteins are reviewed: Formaldehyde-ozone for NH2-terminal tryptophan, formaldehyde-HCl for tryptophan regardless of position in the peptide, OPT for NH2-terminal histidine, formaldehyde-fluorescamine for "protected" amino groups, nitroso-naphthol for tyrosine, and phenanthrenequinone for arginine residues. The methods are potent in demonstrating granule-stored material in peptide hormone-producing cells. Also quinacrine, the fluorescent anti-malaria agent, binds to granular components, as yet unidentified, in several endocrine cell types. In many cases the fluorescence histochemical methods seem to demonstrate peptides and proteins distinct from the known hormones.
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PMID:Fluorescence histochemical methods for the study of peptide hormone-producing cells. 629 61


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