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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 235-kDa rhoptry protein of the rodent malaria parasite Plasmodium yoelii yoelii was shown to bind to the surface of mouse red blood cells in a calcium-independent process, using a erythrocyte-binding assay. This binding is affected by modification of the surface of the red blood cells by enzymatic treatment. Chymotrypsin and trypsin but not neuraminidase treatment of the erythrocytes significantly reduced the binding of the 235-kDa proteins. The binding of an unrelated 135-kDa protein was abolished by treatment with chymotrypsin. Although the 235-kDa proteins bind to both reticulocytes and mature red blood cells, the binding to mature cells was more pronounced. In the presence of hyperimmune infection serum or specific polyclonal antibodies to the 235-kDa protein its binding to erythrocytes was reduced, further demonstrating the specificity of this ligand-receptor interaction.
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PMID:Plasmodium yoelii: effects of red blood cell modification and antibodies on the binding characteristics of the 235-kDa rhoptry protein. 1096 46

Research has not provided unequivocal support for the recommendation to continue breastfeeding until children reach at least age 24 months. In many circumstances, breastfeeding duration is chosen or conditioned by factors other than scientific evidence and recommendations. Even in communities where breastfeeding into the second year is the norm, a significant number of toddlers are weaned before the recommended age. The research reported here was conducted in a rural community of western Kenya. We prospectively followed a cohort of 264 children for 6 months (mean age at baseline, 14.1 +/- 2.4 months) to examine the effect of variable breastfeeding duration on length and weight gain. We found that breastfeeding was positively associated with growth in a manner that we inferred to be causal, the effect being stronger on linear growth than on weight gain. This was despite the fact that in a cohort where 95% were breastfeeding at baseline, the prevalence of stunting (height-for-age below -2 standard deviations of the WHO-NCHS reference) was already 48%. The present paper examines the socioeconomic characteristics, sanitation, morbidity, and complementary feeding practices that define the context of this apparently contradictory relationship. The population was poor, no household had running water, and malaria is endemic in the study area. Complementary feeding was initiated for 93% of the cohort before age 3 months. The weaning diet was bulky (77% energy from carbohydrate), and high in phytate content ([phytate]:[zinc] molar ratio, 28). Diet quality, judged by diversity and animal source food intake, was low. Several micronutrient intakes were below current recommendations, including riboflavin (63%), niacin equivalents (64%), calcium (72%), iron (74%) and zinc (33%). Based on a locally defined socioeconomic status scale, children in higher SES households were breastfed for a shorter duration than were children from poorer households. Sanitation and water consumption modified the effect of breastfeeding duration on growth: the effect was stronger in the absence of a pit latrine and at low water consumption. Our results support the recommendation to sustain breastfeeding in the second year, particularly in economically depressed environments with inadequate sanitation and water supplies.
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PMID:Breastfeeding and growth in rural Kenyan toddlers. 1106 68

Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated haemolysis. Here we report the identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that scavenges haemoglobin by mediating endocytosis of haptoglobin-haemoglobin complexes. CD163 binds only haptoglobin and haemoglobin in complex, which indicates the exposure of a receptor-binding neoepitope. The receptor-ligand interaction is Ca2+-dependent and of high affinity. Complexes of haemoglobin and multimeric haptoglobin (the 2-2 phenotype) exhibit higher functional affinity for CD 163 than do complexes of haemoglobin and dimeric haptoglobin (the 1-1 phenotype). Specific CD163-mediated endocytosis of haptoglobin-haemoglobin complexes is measurable in cells transfected with CD163 complementary DNA and in CD163-expressing myelo-monocytic lymphoma cells.
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PMID:Identification of the haemoglobin scavenger receptor. 1119 22

The properties of the malaria parasite-induced permeability pathways in the host red blood cell have been a major area of interest particularly in the context of whether the pathways are host- or parasite-derived. In the present study, the whole-cell configuration of the patch-clamp technique has been used to show that, compared with normal cells, chicken red blood cells infected by Plasmodium gallinaceum exhibited a 5-40-fold larger membrane conductance, which could be further increased up to 100-fold by raising intracellular Ca(2+) levels. The increased conductance was not due to pathways with novel electrophysiological properties. Rather, the parasite increased the activity of endogenous 24 pS stretch-activated non-selective cationic (NSC) and 62 pS calcium-activated NSC channels, and, in some cases, of endogenous 255 pS anionic channels.
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PMID:Malaria parasite Plasmodium gallinaceum up-regulates host red blood cell channels. 1143 24

Midguts of the malaria-transmitting mosquito, Anopheles stephensi, were homogenized and microvillar membranes prepared by calcium precipitation and differential centrifugation. Oligosaccharides present on the microvillar glycoproteins were identified by lectin blotting before and after in vitro and in situ treatments with endo- and exo-glycosidases. Twenty-eight glycoproteins expressed a structurally restricted range of terminal sugars and oligosaccharide linkages. Twenty-three glycoproteins expressed oligomannose and/or hybrid N-linked oligosaccharides, some with alpha1-6 linked fucose as a core residue. Complex-type N-linked oligosaccharides on eight glycoproteins all possessed terminal N-acetylglucosamine, and alpha- and beta-linked N-acetylgalactosamine. Eight glycoproteins expressed O-linked oligosaccharides all containing N-acetylgalactosamine with or without further substitutions of fucose and/or galactose. Galactosebeta1-3/4/6N-acetylglucosamine-, sialic acidalpha2-3/6galactose-, fucosealpha1-2galactose- and galactosealpha1-3galactose- were not detected. Terminal alpha-linked N-acetylgalactosamine residues on N-linked oligosaccharides are described for the first time in insects. The nature and function of these midgut glycoproteins have yet to be identified, but the oligosaccharide side chains are candidate receptors for ookinete binding and candidate targets for transmission blocking strategies.
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PMID:Partial characterization of oligosaccharides expressed on midgut microvillar glycoproteins of the mosquito, Anopheles stephensi Liston. 1148 30

Hundred confirmed cases of malaria were included in the present study to determine the clinical and prognostic implications of hypocalcemia and corrected QT interval (QTc) prolongation in malaria. Peripheral blood smear examination was done to determine the parasite species and the parasite load. Serum calcium level and QTc measurements in electrocardiogram were done for each patient. Fifty patients were of P. falciparum malaria (38 complicated and 12 uncomplicated), 40 of vivax malaria and 10 patients were having mixed (P. falciparum and P. vivax) infection. Hypocalcemia was found in 26 cases in which QTc was prolonged. Ten patients who had convulsions, all of them were having QTc prolongation and eight had hypocalcemia. A total number of eight patients had muscle spasm, of which six had QTc prolongation and four had hypocalcemia. There were 34 cases of cerebral malaria, of which 18 had hypocalcemia as well as QTc prolongation, 12 of them developed renal failure and 14 had high parasitaemia. Four patients died who had hypocalcemia and QTc prolongation due to hepatorenal syndrome. The mean parasite load, QTc interval and serum calcium were 2.69 +/- 1.0, 0.468 +/- 0.055 sec and 8.16 +/- 0.86 mg/dl respectively in complicated falciparum malaria; 1.6 +/- 0.55, 0.442 +/- 0.043 sec and 8.72 +/- 0.97 mg/dl in complicated mixed (Pf + Pv) infection. 1.33 +/- 0.52, 0.435 +/- 0.035 sec and 9.77 +/- 1.34 mg/dl in uncomplicated falciparum malaria and 1.35 +/- 0.58, 0.403 +/- 0.019 sec and 9.68 +/- 0.99 mg/dl in vivax malaria. The difference was significant between complicated falciparum and mixed (Pf + Pv) infection when compared to uncomplicated falciparum and vivax malaria (p < 0.05).
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PMID:Prognostic implication of hypocalcemia and QTc interval in malaria. 1182 87

Once ingested by mosquitoes, malaria parasites undergo complex cellular changes. These include zygote formation, transformation of zygote to ookinete, and differentiation from ookinete to oocyst. Within the oocyst, the parasite multiplies into numerous sporozoites. Modulators of intracellular calcium homeostasis, MAPTAM, and TMB-8 blocked ookinete development as did the calmodulin (CaM) antagonists W-7 and calmidazolium. Ca(2+)/CaM-dependent protein kinase inhibitor KN-93 also blocked zygote elongation, while its ineffective analog KN-92 did not have such effect. In vitro both zygote and ookinete extracts efficiently phosphorylated autocamtide-2, a classic CaM kinase substrate, which could be blocked by calmodulin antagonists W-7 and calmidazolium and CaM kinase inhibitor KN-93. These results demonstrated the presence of calmodulin-dependent CaM kinase activity in the parasite. KN-93-treated parasites, however, expressed the ookinete-specific enzyme chitinase and the ookinete surface antigen Pgs28 normally, suggesting that the morphologically untransformed parasites are biochemically mature ookinetes. In mosquitoes, KN-93-treated parasites did not develop as oocysts, while KN-92-treated parasites produced similar numbers of oocysts as controls. These data suggested that in Plasmodium gallinaceum morphological development of zygote to ookinete, but not its biochemical maturation, relies on Ca(2+)/CaM-dependent protein kinase activity and demonstrated that the morphological differentiation is essential for the further development of the parasite in infected blood-fed mosquitoes.
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PMID:Inhibition of Ca2+/calmodulin-dependent protein kinase blocks morphological differentiation of plasmodium gallinaceum zygotes to ookinetes. 1182 60

Guanylyl cyclases in eukaryotic unicells were biochemically investigated in the ciliates Paramecium and Tetrahymena, in the malaria parasite Plasmodium and in the ameboid Dictyostelium. In ciliates guanylyl cyclase activity is calcium-regulated suggesting a structural kinship to similarly regulated membrane-bound guanylyl cyclases in vertebrates. Yet, cloning of ciliate guanylyl cyclases revealed a novel combination of known modular building blocks. Two cyclase homology domains are inversely arranged in a topology of mammalian adenylyl cyclases, containing two cassettes of six transmembrane spans. In addition the protozoan guanylyl cyclases contain an N-terminal P-type ATPase-like domain. Sequence comparisons indicate a compromised ATPase function. The adopted novel function remains enigmatic to date. The topology of the guanylyl cyclase domain in all protozoans investigated is identical. A recently identified Dictyostelium guanylyl cyclase lacks the N-terminal P-type ATPase domain. The close functional relation of Paramecium guanylyl cyclases to mammalian adenylyl cyclases has been established by heterologous expression, respective point mutations and a series of active mammalian adenylyl cyclase/ Paramecium guanylyl cyclase chimeras. The unique structure of protozoan guanylyl cyclases suggests that unexpectedly they do not share a common guanylyl cyclase ancestor with their vertebrate congeners but probably originated from an ancestral mammalian-type adenylyl cyclase.
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PMID:Guanylyl cyclases in unicellular organisms. 1195 90

Serine proteases play crucial roles in erythrocyte invasion by merozoites of the malaria parasite. Plasmodium falciparum subtilisin-like protease-1 (PfSUB-1) is synthesized during maturation of the intraerythrocytic parasite and accumulates in a set of merozoite secretory organelles, suggesting that it may play a role in host cell invasion or post-invasion events. We describe the production, purification, and characterization of recombinant PfSUB-1 and comparison with the authentic protease detectable in parasite extracts. The recombinant protease requires high levels of calcium for optimum activity and has an alkaline pH optimum. Using a series of decapeptide and protein substrates, PfSUB-1 was found to have a relaxed substrate specificity with regard to the P1 position but is unable to efficiently cleave substrates with a P1 leucine residue. Similarly, replacement of a P4 valine with alanine severely reduced cleavage efficiency, whereas its replacement with lysine abolished cleavage. In all respects investigated, the recombinant protease was indistinguishable from parasite-derived enzyme. Three-dimensional homology modeling of the PfSUB-1 catalytic domain based on an alignment with closely related bacterial subtilisins and an orthologue from the rodent malaria Plasmodium yoelii suggests that the protease has at least three potential calcium ion-binding sites, three intramolecular disulfide bridges, and a single free cysteine within the enzyme S1 pocket. A predicted highly polar S1 pocket and a hydrophobic S4 subsite are in broad agreement with the experimentally determined substrate specificity.
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PMID:Expression of recombinant Plasmodium falciparum subtilisin-like protease-1 in insect cells. Characterization, comparison with the parasite protease, and homology modeling. 1205 28

There were 67.76 million persons belonging to scheduled tribes in about 74 distinct groups in India in 1991, or 7.95% of total population, usually living in remote and ecologically diverse climates and areas. Modern medicine has not been accepted in most tribal areas, where magico-religious health care systems prevail. Health conditions in tribal areas have been described as deficient in sanitary conditions, personal hygiene, and health education. Common diseases are sexually transmitted ones and genetic abnormalities such as sickle cell anemia and Glucose-6 Phosphate Enzyme Deficiency (G-6-PD). Disease incidence for sickle cell anemia has been estimated at more than 19% among 35 tribal population groups. 5 million are estimated to be carriers. G-6-PD shows a genetically carried deficiency in a blood enzyme; persons commonly reject antimalarials, antibiotics, and analgesics. The population estimated to have the deficiency is about 13 million, primarily residing in Madhya Pradesh, Maharashtra, Tamil Nadu, Orissa, and Assam states (15%). The incidence is high in malaria zones. Screening kits are needed by health workers, so that identified people can be tattooed and high risk families counseled accordingly. The Onges, Jarawas, and Shompens of Andaman and Nicobar Islands are facing extinction due to endemic diseases, venereal diseases, and a shortage of women. Health workers need information on the folklore related to health of these and other tribal groups, in order to provide appropriate health and sanitary practices and to document indigenous herbs for medical use. Malnutrition is pervasive among tribals. Deficiencies have been detected in gross amounts of calcium, vitamin A, vitamin C, riboflavin, and animal protein. Southern tribes are known for their caloric and protein deficiencies. Those in rice-eating belts tend to have had higher protein intake. The workload of tribal women is heavy, long, and increasing. Maternal mortality is due to unhygienic conditions and inappropriate tribal practices. Interventions must focus on tribal culture, medical training of indigenous people, a health care delivery system catering to the community needs, and more research.
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PMID:A health profile of tribal India. 1228 63


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