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)

The present study included 426 patients with acute renal failure age range 7 months to 85 years, during 8-year period (1984-1992). Medical, surgical and obstetric causes were responsible for ARF in 68.3, 17.8, and 14% of cases respectively. The main aetiological factors encountered were volume depletion secondary to gastrointestinal fluid loss (35.2%), acute glomerulonephritis (10.3%), nephrotoxin (8.6%), falciparum malaria (4.2%), obstructive uropathy (13%), post-abortal (10.5%), and miscellaneous factors (1.4%) of patients. The overall mortality was 19.2%. Thus our observation revealed that diarrhoeal diseases (35.2%), obstructive uropathy (13.3%), and septic abortion (10.5%) were the main causes for ARF in medical, surgical, and obstetric groups respectively. In contrast to our studies, acute renal failure associated with diarrhoeal diseases, septicaemia, falciparum malaria and septic abortion are rare in European countries.
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PMID:Acute renal failure in eastern India. 864 59

The malaria parasite Plasmodium falciparum has an unusual organization of its secretory compartments. As an approach to a functional identification of auxiliary proteins involved in secretion, a parasite line was generated by drug selection that is resistant to brefeldin A, an inhibitor of the secretory pathway. In the resistant line, neither protein secretion nor parasite viability were affected by the drug. The analysis of a sec7 domain, a conserved structure of guanine nucleotide exchange factors (ARF-GEF) required for the activation of ADP-ribosylation factors, revealed a single methionine-isoleucine substitution in the resistant parasite line. ARF-GEFs are key molecules in the formation of transport vesicles and the main targets of brefeldin A. The methionine residue in this position of sec7 domains is highly conserved and confers brefeldin A sensitivity. Unlike other eukaryotes that have multiple ARF-GEFs, the plasmodial genome encodes a single sec7 domain. This domain shows a distinct structural difference to all sec7 domains analysed so far; two conserved subdomains that are essential for protein function are separated in the plasmodial protein by an insertion of 146 amino acids.
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PMID:A point mutation in an unusual Sec7 domain is linked to brefeldin A resistance in a Plasmodium falciparum line generated by drug selection. 1155 94

A case of failed peritoneal dialysis in a 5-year-old male nephrotic who developed acute renal failure following severe P. falciparum malaria infection is presented. Peritoneal dialysis (PD) failure was sequel to undetected severe dehydration which occurred during the diuretic phase of the acute renal failure. Pre-dialysis plasma potassium, bicabonate, urea and creatinine concentrations were 6.0mmol/L, 13mmol/L, 28mmol/L and 900mmol/L respectively, after about 22 hours of PD, the plasma K+, HCO-3 Ur and Cr were 5.7mmol/L, 15mmol/L, 32mmol/L and 1,090mml/L respectively. The peritoneal dialysate Ur concentration (3.5mmol and peritoneal Ur clearance (1.85ml/min/1.73m2) were grossly inadequate. There was also, intradialysis hyperglycaemia (12mmol/L owing to massive absorption of peritoneal dialysate solution which contains high concentration of glucose. Hyperglycaemia was corrected with 0.25 units/kg/dose of soluble insulin intravenously, he had two doses. Owing to similarity of clinical and biochemical features of dehydration and ARF, all efforts must be made to exclude dehydration before embarking on PD in patients with renal failure. Failure to exclude dehydration, led to PD failure in this patient.
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PMID:Failed peritoneal dialysis in a dehydrated nephrotic child, in acute renal failure: a case report. 1250 Dec 70

GTPase activating protein for ARF GTPAse (ARFGAP) from the malaria parasite Plasmodium falciparum was expressed, purified and crystallized. Crystals of ARFGAP belong to trigonal space group P321 (or its enantiomorph) with unit cell parameters a=b=95.89 and c=92.46 A. Diffraction data to 2.4-A resolution have been collected. Calculation of self-rotation function suggested the presence of two molecules in the asymmetric unit.
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PMID:Plasmodium falciparum ARFGAP: expression and crystallization of the catalytic domain. 1506 23

High molecular weight ADP ribosylation factor GDP-GTP exchange factors (ARF-GEF) play an essential role in the formation of COP I coated transport vesicles and are characterized by a structurally and functionally conserved sec 7 domain. The genome of the malaria parasite Plasmodium falciparum encodes a single ARF-GEF that contains an unusual sec 7 domain. In comparison to the sec 7 domain of other eukaryotes, the plasmodial sec 7 domain is characterized by an insertion sequence of 146 amino acids that disrupt helices essential for the GDP-GTP exchange activity of the protein. In a previous study we have shown a correlation between a methionine to isoleucine exchange in helix H of the sec 7 domain and resistance to brefeldin A in a parasite line generated by drug selection. Here we have transfected brefeldin A sensitive parasites with plasmid constructs containing the sec 7 domain of the resistant line either with or without the insertion sequence. Transfection with sec 7 sequences including the insertion resulted in brefeldin A resistant parasites in which double cross-over recombination had replaced the endogenous sec 7 sequences with the transgenic sequences. Thus, the point mutation in helix H is sufficient to confer brefeldin A resistance in P. falciparum. Transfections using constructs lacking the insertion did not result in resistant parasites. Gene replacement by targeted double cross-over recombination is a rare event in P. falciparum. This approach has taken advantage of the fact that the successful integration of the transgene results in a drug selectable phenotype. We anticipate that the strategy described here will be useful for the identification of mutations within target genes that have the potential to confer increased drug resistance.
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PMID:Double cross-over gene replacement within the sec 7 domain of a GDP-GTP exchange factor from Plasmodium falciparum allows the generation of a transgenic brefeldin A-resistant parasite line. 1550 Sep 15

Burkitt lymphoma (BL), a tumor occurring in endemic, sporadic and AIDS-associated forms, is the classic example of a human malignancy whose pathogenesis involves a specific cellular genetic change, namely, a chromosomal translocation deregulating expression of the c-myc oncogene, complemented in many cases by the action of an oncogenic virus, the Epstein-Barr virus (EBV). Here we review recent work in two complementary areas of research: (1) on cellular genetic changes that occur in addition to the c-myc translocation in BL, in particular the capacity of p53/ ARF pathway breakage or of c-myc mutation to decouple the pro-proliferative effects of c-myc deregulation from its pro-apoptotic effects; and (2) on a postulated role for EBV in BL pathogenesis, through adopting restricted forms of virus latent gene expression that remain compatible with the c-myc-driven growth program but offer the tumor additional protection from apoptosis. We stress the many fundamental questions that remain to be resolved and, in that regard, highlight the general lessons that might be learned through understanding how two other infectious agents, malaria and HIV, dramatically enhance BL incidence.
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PMID:Burkitt lymphoma: revisiting the pathogenesis of a virus-associated malignancy. 1802 41

In eukaryotes, calcium signalling has been linked to hydrolysis of the phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). The final enzyme in the synthesis of this phosphoinositide, a Type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K), is activated by the small G protein ADP-ribosylation factor 1 (ARF1). In mammals, the ARF-PIP5K pathway is a key regulator of cell motility, secretion and cell signalling. We report the characterisation of a unique, putative bifunctional PIP5K in the human malaria parasite Plasmodium falciparum. The protein comprises a C-terminal, functional PIP5K domain with catalytic specificity for phosphatidylinositol 4-phosphate. The recombinant enzyme is activated by ARF1 but not phosphatidic acid. The protein also incorporates an unusual N-terminal domain with potential helix-loop-helix EF-hand-like motifs that is a member of the neuronal calcium sensor family (NCS). Intriguingly, NCS-1 has been shown to stimulate phosphatidylinositol 4-phosphate synthesis by activating mammalian and yeast phosphatidylinositol 4-kinase beta in vitro in a calcium-dependent manner. The unexpected physical attachment of an NCS-like domain to the plasmodial PIP5K might reflect a unique functional link between the calcium and PtdIns(4,5)P(2) pathways allowing modulation of PtdIns(4,5)P(2) production in response to changes in intracellular calcium concentrations within the parasite.
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PMID:A unique phosphatidylinositol 4-phosphate 5-kinase is activated by ADP-ribosylation factor in Plasmodium falciparum. 1917 Nov 50