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

The fluorescent indicator, fura-2, AM, was used to measure free calcium concentrations in the intraerythrocytic malaria parasites of Plasmodium chabaudi and Plasmodium falciparum. In both species the free cytosolic calcium concentration was maintained at low levels (between 40 and 100 nM throughout the maturation process. Digital image analysis of the indicator fluorescence was performed on parasites and evaluated with the aid of a calibration of the calcium response, based on permeabilized parasites, exposed to calcium buffers. This again revealed that free calcium concentrations in the intact parasite are maintained at a predetermined level, regardless of the free calcium in the surrounding milieu. Both species of parasites are thus capable of regulating their internal free calcium levels with high precision, presumably by means of calcium pump ATPases. A small but significant elevation of the cytosolic free calcium concentration by the tumor promoter, thapsigargin, may be taken to reflect the presence of calcium stores in the endoplasmic reticulum in P. falciparum.
 ...
PMID:Calcium homeostasis in intraerythrocytic malaria parasites. 898 Sep 13

The perturbation of various glycosylphosphatidylinositol (GPI)-anchored surface proteins imparts profound regulatory signals to macrophages, lymphocytes and other cell types. The specific contribution of the GPI moieties to these events however is unclear. This study demonstrates that purified GPIs of Plasmodium falciparum, Trypanosoma brucei, and Leishmania mexicana origin are sufficient to initiate signal transduction when added alone to host cells as chemically defined agonists. GPIs (10 nM-1 microM) induce rapid activation of the protein tyrosine kinase (PTK) p59(hck) in macrophages. The minimal structural requirement for PTK activation is the evolutionarily conserved core glycan sequence Man alpha1-2Man alpha1-6Man alpha1-4GlcN1-6myo-inositol. GPI-associated diacylglycerols independently activate the calcium-independent epsilon isoform of protein kinase C. Both signals collaborate in regulating the downstream NF-kappa B/rel-dependent gene expression of interleukin 1alpha, tumor necrosis factor (TNF) alpha, and inducible NO synthase. The alkylacyl-glycerol-containing iM4 GIPL of L. mexicana, however, is unable to activate protein kinase C and inhibits TNF expression in response to other agonists, establishing signaling specificity among structurally distinct GPIs. GPI alone appears sufficient to mimic the activities of malaria parasite extracts in the signaling pathway leading to TNF expression. A mAb to GPI blocks TNF induction by parasite extracts indicating that GPI is a necessary agent in this response. As protozoal GPIs are closely related to their mammalian counterparts, the data indicate that GPIs do indeed constitute a novel outside-in signaling system, acting as both agonists and second messenger substrates, and imparting at least two separate signals through the structurally distinct glycan and fatty acid domains. These activities may underlie aspects of pathology and immune regulation in protozoal infections.
 ...
PMID:Signal transduction in macrophages by glycosylphosphatidylinositols of Plasmodium, Trypanosoma, and Leishmania: activation of protein tyrosine kinases and protein kinase C by inositolglycan and diacylglycerol moieties. 910 98

The most frequent hepatobiliary diseases in Vietnam are chronic hepatitis and cirrhosis, liver abscess, hepatobiliary ascaridiasis, angiocholitis, biliary lithiasis and primary liver cancer. The principal causes of chronic hepatitis and cirrhosis are HBV and HCV infections. Alcohol and chemicals (drugs, agricultural, industrial, war herbicides) also play an important role. Malaria causes hepatitis and fibrosis lesions, however no cirrhotic lesions were observed. There are two categories of liver abscess, amoebic and cholangitic, often caused by ascaridiasis. Treatment of amoebic abscesses is, at first, non-surgical for small abscesses, often combined with ultrasound guided abscess puncture. Cholangitis abscesses are more serious and often require surgical intervention. Among the gallstones, only 15% are of the gall-bladder, the majority are choledocho- and intrahepatic-lithiasis, composed largely of calcium bilirubinate and are frequently caused by Ascaris-related cholangitis and the nucleation of Ascaris eggs. Forty-seven per cent of acute cholecystitis are acalculous, showing a higher frequency than in Western countries. Primary liver cancer is one of the most frequent malignancies in Vietnam. More than 90% of liver cancers are hepatocellular carcinomas. The principal causes are HBV infection, followed by HCV infection, aflatoxin, alcohol and chemicals. Recent efforts aiming at earlier diagnosis, by selective screening in high-risk groups, have used clinical surveillance, abdominal sonography and AFP level determination. Promising results were obtained in prevention trials by reducing the high AFP level of cirrhotic patients using a vegetal drug, Gacavit, and by treatment with percutaneous ethanol injection therapy, as an alternative therapeutic measure for liver tumour resection.
 ...
PMID:Some peculiarities of hepatobiliary diseases in Vietnam. 919 96

Presence of Plasmodium falciparum parasites in the peripheral blood of patients in a holoendemic area does not necessarily show that their illness is due to malaria. The aim of the present project was therefore to look for biological markers related to symptomatology or clinical events during a malaria episode. We focused our work on a complex of heterodimeric calcium-binding proteins secreted by stimulated neutrophils and monocytes, named MIF or myeloid-related proteins (MRP 8/14). In a longitudinal study including 51 adults from Ifakara, Tanzania (84.7% prevalence for P. falciparum in adults during the study), the level of MRP 8/14 in the serum was significantly related to the parasite load (Spearman correlation coefficient, 0.52; P < 0.0001). In the serum from children up to 6 years admitted at a health post the MRP 8/14 levels were closely related to parasitemia but also to fever episodes (Spearman correlation coefficients, 0.96 and 0.736; P < 0.0001 and P < 0.001, respectively). Although not specific to malaria, the measurement of MRP 8/14 could be an additional tool in assessing malaria-related morbidity.
 ...
PMID:MRP 8/14 as marker for Plasmodium falciparum-induced malaria episodes in individuals in a holoendemic area. 922 Jan 60

Non-mitochondrial calcium deposits were investigated in the intraerythrocytic malaria parasite Plasmodium chabaudi at the trophozoite stage by means of arsenazo III in the presence of ATP and the mitochondrial poisons, antimycin and oligomycin. Addition of vanadate and 2,5-di-(t-butyl)-1,4-hydroquinone (BHQ), both known to interact with SERCA pump, induced calcium release by permeabilized parasites when the medium free calcium concentration was kept at 3.5 microM. The tumor promoter thapsigargin also caused elevation of the free calcium concentration in permeabilized parasites. Our results support the view that P. chabaudi sequesters calcium in an exchangeable form and maintains its calcium homeostasis by way of an endoplasmic reticulum Ca2+ pump.
 ...
PMID:Characterization of Ca2+ transport activity associated with a non-mitochondrial calcium pool in the rodent malaria parasite P. chabaudi. 928 59

The morbidity associated with malaria plays a key role in the staggering of the social and economic development of human race. The investigations on the cellular, biochemical and molecular organisation of the malarial parasite are important to understand the host parasite interactions in a better way. The parasite induces several biochemical and biophysical alterations in the host red cells. It is well recognized that cation homeostasis is vital to basic aspects of cell functions. Though the pathogenesis of anaemia associated with Plasmodium falciparum infection is multifactorial, the complex mechanisms involving the role of oxidant stress and calcium imbalance of infected red cells plays an important role.
 ...
PMID:Biochemical changes induced by malarial parasites. 929 78

Malaria-parasitized erythrocytes have increased endothelial adherence due to exposure of previously buried intramembranous sites of band 3. Because sickle erythrocytes also show increased adhesiveness and because the membrane portion of band 3 is aggregated in both types of cells, we examined the role of band 3 in sickle cell adhesiveness. Synthetic peptides derived from the second and third exofacial, interhelical regions of band 3 completely inhibited the abnormal adherence of sickle cells to an endothelial monolayer in a static assay. This effect was observed independently of plasma factors, required micromolar levels of peptide, was sequence-specific, and was found with both L- and D-isomers. The active peptides also inhibited the increased adherence induced by low-dose calcium loading of normal red blood cells. Finally, a monoclonal antibody against an active peptide specifically immunostained a fraction of sickle cells. These findings implicate a role for band 3 in at least one type of sickle cell adhesiveness via the exposure of normally cryptic membrane sites.
 ...
PMID:Band 3 peptides block the adherence of sickle cells to endothelial cells in vitro. 935 88

An endoplasmic reticulum-located, calcium-binding protein, with an apparent molecular weight (Mr) of approximately 40,000 (PfERC), has been identified in the asexual stages of the malaria parasite, Plasmodium falciparum. This protein appears to be equivalent to a previously described gametocyte protein, Pfs40, which was reported to be expressed on the gametocyte surface (Rawlings DJ, Kaslow DC. J Biol Chem 1992;267:3976-3982). Sequencing of the 3' end of the gene revealed the omission of a single base in the 3' region of the published sequence. The corrected gene sequence encodes a C-terminal IDEL motif, which indicates residency of the 40 kDa protein within the endoplasmic reticulum. The predicted C-terminal region also appears to contain a sixth EF-hand calcium-binding domain, which suggests that PfERC is related to previously reported ER-localized calcium-binding proteins, namely reticulocalbin and ERC-55 (Ozawa M. J. Biochem. 1995;117:1113-1119; Weis K, Griffiths G, Lamond AI. J. Biol. Chem. 1994;269:19142-19150). The presence of the 40 kDa calcium-binding protein in malaria parasites was confirmed using 45Ca2+-blotting and partial protein sequencing of the corresponding Coomassie blue-stained polypeptide. Confocal immunofluorescence microscopy of asexual stage parasites was used to show that PfERC co-localizes with the known ER-located protein, Pfgrp. Analysis of immunoblots of tightly synchronized parasites showed that expression of PfERC increases with increasing maturity of the parasite. We propose that PfERC is a member of the reticulocalbin family of calcium-binding proteins and may play a role in protein trafficking in the malaria parasite.
 ...
PMID:Identification of an endoplasmic reticulum-resident calcium-binding protein with multiple EF-hand motifs in asexual stages of Plasmodium falciparum. 936 72

A 53-year-old female suffering from severe anaemia following falciparum malaria required blood transfusion. Her blood specimen in EDTA showed strong autoagglutination giving problems in the preliminary grouping by a slide test. She was grouped, however, as B Rh-D positive without difficulty by the cell and serum groupings done using clotted blood. Two units of B Rh-D positive blood compatible with the patient's serum were transfused without untoward reaction. The patient's blood collected a fresh in different anticoagulants showed autoagglutination in the plasma with EDTA or citrate, but not in heparin collection or in serum, indicating a possible role of ionized calcium as an inhibitor of reactivity. Addition of 0.02 M calcium chloride solution to the plasma remarkably weakened the strength of agglutination, evidently supporting this hypothesis. Autoantibody, identified as anti-Pra, was transient in nature and possibly associated with the malarial infection, as neither the antibody nor the malarial parasites were detected in her blood in follow up studies four months later.
 ...
PMID:Reactivity of a transient autoantibody inhibited by ionized calcium. 940 70

Malaria-infected red blood cells are under a substantial oxidative stress. Glutathione metabolism may play an important role in antioxidant defense in these cells, as it does in other eukaryotes. In this work, we have determined the levels of reduced and oxidized glutathione (GSH and GSSG, respectively) and their distributions in the parasite, and in the host-cell compartments of human erythrocytes infected with the malaria parasite Plasmodium falciparum. In intact trophozoite-infected erythrocytes, [GSH] is low and [GSSG] is high, compared with the levels in normal erythrocytes. Normal erythrocytes and the parasite compartment display high GSH/GSSG ratios of 321.6 and 284.5, respectively, indicating adequate antioxidant defense. This ratio drops to 26.7 in the host-cell compartment, indicating a forceful oxidant challenge, the low ratios resulting from an increase in GSSG and a decline in GSH concentrations. On the other hand, the concentrations of GSH and GSSG in the parasite compartment remain physiological and comparable to their concentrations in normal red blood cells. This results from de novo glutathione synthesis and its recycling, assisted by the intensive activity of the hexose monophosphate shunt in the parasite. A large efflux of GSSG from infected cells has been observed, its rate being similar from free parasites and from intact infected cells. This result suggests that de novo synthesis by the parasite is the dominating process in infected cells. GSSG efflux from the intact infected cell is more than 60-fold higher than the rate observed in normal erythrocytes, and is mediated by permeability pathways that the parasite induces in the erythrocyte's membrane. The main route for GSSG efflux through the cytoplasmic membrane of the parasite seems to be due to a specific transport system and occurs against a concentration gradient. Gamma-glutamylcysteine [Glu(-Cys)] and GSH can penetrate through the pathways from the extracellular space into the host cytosol, but not into that of the parasite. This implies that the parasite membrane is impermeable to these peptides, and that the host cannot supply GSH to the parasite as suggested previously. Exogenous Glu(-Cys) is not converted into GSH in the host cell, arguing that GSH synthetase may not be functional. Compartment analysis of Mg2+ in infected erythrocytes revealed that the host compartment exhibits a low concentration of Mg2+ (0.5 mM) in comparison with the parasite compartment (4 mM) and the normal erythrocytes (1.5-3 mM). The drop in [Mg2+] results in cessation of Glu(-Cys) synthesis, and hence of GSH synthesis in the host-cell compartment. The decrease in [Mg2+] can affect other Mg2+-ATP-dependent functions, such as Na+ and Ca2+ active efflux. The present investigation confirms that the host-cell compartment is oxidatively distressed, whereas the parasite is efficiently equipped with anti-oxidant means that protect the parasite from the oxidative injury. The parasite has a huge capacity for de novo synthesis of GSH and for the reduction of GSSG. Part of the GSSG that is actively extruded from the parasite is reduced to GSH in the host cell whose own GSH synthesis is crippled.
 ...
PMID:The malaria parasite supplies glutathione to its host cell--investigation of glutathione transport and metabolism in human erythrocytes infected with Plasmodium falciparum. 946 Dec 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>