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)

To demonstrate the liver profile abnormalities in jaundiced falciparum malaria patients and to determine whether jaundice was associated with other complications in falciparum malaria, 390 patients with acute falciparum malaria were studied. 124 patients were jaundiced and the others were non-jaundiced. Hyperbilirubinemia (total serum bilirubin 3 to 64 mg/dl) was found in jaundiced patients predominantly as unconjugated bilirubin. Asparatate amino-transferase and alanine minotransferase were significantly higher in jaundiced patients (p < 0.01). There was a slight decrease of serum albumin in jaundiced malaria. The complications in jaundiced patients included cerebral malaria (n = 10), acute renal failure (n = 12), pulmonary edema (n = 3), shock (n = 3), and other severe malarial complications (n = 43). Jaundice was associated with cerebral malaria (p < 0.05), acute renal failure (p < 0.01), and hyperparasitemia (p < 0.01). After successful treatment, liver profile returned to normal within a few weeks. We found that jaundiced malaria patients had transient liver profile impairment which indicated predominantly hemolysis rather than liver damage; complications were more frequent in jaundiced patients.
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PMID:Liver profile changes and complications in jaundiced patients with falciparum malaria. 771 91

One approach towards the development of a vaccine against malaria is to immunize against the parasite sexual stages that mediate transmission of the parasite from man to mosquito. Antibodies against these stages, ingested with the blood meal, inhibit the parasite development in the mosquito vector, constituting "transmission blocking immunity." Most epitopes involved in transmission-blocking immunity depend on the tertiary conformational structure of surface antigens. However, one of the transmission-blocking monoclonal antibodies we have raised against Plasmodium vivax reacts with a linear epitope on both asexual stages and gametes. This monoclonal antibody (A12) is capable of totally blocking development of the parasite in the mosquito host when tested in membrane feeding assays with gametocytes from P. vivax-infected patients. Immune screening of a P. vivax lambda gt11 genomic expression library with A12 led to the isolation of a clone to which was mapped the six-amino acid epitope recognized by A12. Antisera raised in mice against a 12-mer synthetic peptide containing this epitope coupled to bovine serum albumin not only had high titers of antipeptide antibodies as measured by enzyme-linked immunosorbent assay, but in addition recognized the same 24- and 57-kD parasite components as A12 on Western blots and reacted with the parasite by immunofluorescence. When tested in membrane feeding assays, these antibodies have significant suppressive effects on parasite development in the mosquito.
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PMID:Transmission blocking immunity in Plasmodium vivax malaria: antibodies raised against a peptide block parasite development in the mosquito vector. 780 16

A novel expression system for surface display of heterologous proteins on Staphylococcus carnosus cells has been developed. Taking advantage of the promoter and secretion signals, including a propeptide region, from the lipase gene of Staphylococcus hyicus and the cell wall-spanning and membrane-binding region of protein A from Staphylococcus aureus, efficient surface display of an 80-amino-acid peptide from a malaria blood stage antigen could be achieved. A serum albumin binding protein from streptococcal protein G was used both as a general reporter molecule and to increase the accessibility of the surface-displayed proteins. Immunoblotting, immunogold staining, and immunofluorescence on intact recombinant S. carnosus cells verified the presence of the propeptide, the malaria antigen, and the albumin-binding reporter protein on the bacterial surface. For the first time, fluorescence-activated cell sorting was used to analyze the presence of surface-displayed hybrid receptors on gram-positive bacteria.
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PMID:Cell surface display of recombinant proteins on Staphylococcus carnosus. 788 2

Gangliosides are known to be suitable targets for immune attack against cancer but they are poorly immunogenic. Active immunization with ganglioside/BCG or liposome vaccines results in moderate titer IgM antibody responses of short duration. Covalent attachment of poorly immunogenic antigens to immunogenic proteins is a potent method for inducing an IgG antibody response. GD3, a dominant ganglioside on malignant melanoma, was modified by ozone cleavage of the double bond in the ceramide backbone, an aldehyde group introduced and used for coupling via reductive amination to epsilon-amino-lysyl groups of proteins. Utilizing this method, GD3 conjugates were constructed with: 1. Synthetic multiple antigenic peptide (MAP) constructs expressing 4 repeats of a malaria T-cell epitope; 2. Outer membrane proteins (OMP) of Neisseria meningitidis; 3. Cationized bovine serum albumin; 4. Keyhole limpet hemocyanin (KLH); and 5. Polylysine. In addition, conjugates containing only the GD3 oligosaccharide were synthesized. All constructs were tested for antigenicity using anti-GD3 antibody R24, and for immunogenicity in mice. Serum antibody levels were analyzed by ELISA and immune thin-layer chromatography. Results in the mouse show a significant improvement in the IgM antibody response and a consistent IgG response against GD3 using GD3-KLH conjugates. Other carrier proteins and the use of GD3 oligosaccharide were significantly less effective. If improved immunogenicity and clinical benefit with conjugate vaccines can be demonstrated in patients with melanoma, this approach may be applicable to patients with other tumors of neuroectodermal origin, including gliomas, glioblastomas, astrocytomas, and neuroblastomas.
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PMID:Ganglioside conjugate vaccines. Immunotherapy against tumors of neuroectodermal origin. 808 40

The specificity of murine antibodies raised against structurally related peptides derived from a malaria parasite membrane protein was studied. The peptides were conjugated to bovine serum albumin (BSA) with 6-maleimido caproic acyl N-hydroxysuccinimide ester before immunization. Conjugation to BSA through a C-terminal or an internal cysteine residue elicited antibodies with noticeably different specificities. An N-terminal tripeptide sequence arginine-asparagine-asparagine had a dominant influence on the immunogenicity of the peptides. Such factors need to be taken into consideration while designing peptide-based immunogens.
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PMID:Influence of N-terminal amino acids & conjugation position to carrier on specificities of antibodies elicited by malaria peptides. 816 97

389 pregnant women admitted for full- term, uncomplicated delivery at the Regional Hospital on the island of Zanzibar (Tanzania) were recruited to study the effect of malarial infection on birth weight in an endemic area. 3.8% of all newborns weighed less than 2500 g (i.e., low birth weight [LBW]). 21.4% of all women had peripheral parasitemias but no active placental infection. 17.6% had active placental infection but no peripheral parasitemia. 47.9% had both active placental and peripheral infections. Logistic regression analysis revealed that active placental infection was associated with LBW (15.5% vs. 1.2%; relative risk [RR] = 10.1, population attributable proportion [PAP] = 61.4%; p = 0.003). Serum albumin level less than 2.5 mg/dl was also associated with LBW (11.8% vs. 1.2%; RR= 10.2, PAP = 61.%; p = 0.008). Overall malarial infection was associated with LBW (6.5% vs. 1.8%; RR = 3.5; PAP = 55.4%; p = 0.04). These findings suggest that placental malaria causes intrauterine growth retardation, leading to LBW newborns and that malarial preventive interventions in pregnant women are needed in Tanzania.
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PMID:Malarial infection and birthweight in urban Zanzibar, Tanzania. 876 2

In this study, we have explored the use of the serum albumin-binding region (BB) from streptococcal protein G (SpG) as a bacterial fusion partner for production of peptide immunogens. The fusion protein BB-M3, containing BB and repeated structures from the Plasmodium falciparum malaria antigen Pf155/RESA, was efficiently purified from Escherichia coli culture supernatants by affinity chromatography using BB as an affinity tag. Rabbits immunized with BB-M3 in Freund's adjuvant produced high levels of antibodies which reacted with both M3 and BB in ELISA and stained intact Pf155/RESA in the membrane of infected erythrocytes. These antibody levels were sustained for more than 30 weeks. BB-M3 also induced antibody responses to M3, BB and intact Pf155/RESA in a number of mouse strains, including several strains which are non-responders to the malaria sequences. In the latter mice, however, BB-M3 only activated BB-specific T cells, suggesting that BB has ability to provide carrier-related T cell help for antibody production. Moreover, the minimal albumin-binding motif of SpG, containing only 46 amino acids, was immunogenic in both B10.BR, B10.D2 and C57BL/6 mice (H-2k, H-2d and H-2b, respectively). These results indicate that BB has both affinity tag and carrier-related properties and suggest that fusion proteins containing BB can be efficient tools for the generation of antibody responses to peptides which are weak immunogens.
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PMID:The serum albumin-binding region of streptococcal protein G: a bacterial fusion partner with carrier-related properties. 903 14

A study of 152 rural Malawian women aged 23.2+/-5.5 y (x+/-SD) at 24 wk gestation included measurements of biochemical indexes of zinc (plasma and hair), protein (serum albumin), and infection (serum C-reactive protein, white blood cell count, and malaria), and dietary intakes (via three interactive 24-h dietary recalls). Data on health, demographic and socioeconomic status, family characteristics, reproductive history, and anthropometry were also collected. The study revealed a high prevalence of suboptimal zinc status: 36% of the women had low plasma and 46% had low hair zinc values. Median daily intake of zinc (9.0 mg) was low and poorly available: 61% was provided by cereals and 20% by flesh foods. Median intake of animal protein was only 5.6 g/d, and phytate intakes were high (1.4 g/d). Women consuming diets with phytate-zinc ratios > 17 (the median) had lower hair zinc concentrations (1.6 compared with 1.8 micromol/g, P < 0.03), were older (24 compared with 20 y, P < 0.02), and had a higher number of pregnancies (3 compared with 2, P < 0.02) than those consuming diets with a phytate-zinc ratio < 17. Frequent reproductive cycling was related to zinc status; hair zinc was higher for a prima- than for a multigravida (2.0 compared with 1.6 micromol/g, P < 0.01). Malaria prevalence was also associated with hair zinc (P < 0.05) but not with plasma zinc, after the number of pregnancies was controlled for. We conclude that low intakes of poorly available dietary zinc, frequent reproductive cycling, and malaria prevalence are three major factors in the etiology of suboptimal zinc status in these rural, pregnant Malawian women.
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PMID:Suboptimal zinc status in pregnant Malawian women: its association with low intakes of poorly available zinc, frequent reproductive cycling, and malaria. 953 17

To determine the course of anaemia following treatment for acute falciparum malaria, 72 adult Thai patients were followed for 4 weeks after starting effective therapy. Using the criteria of haemoglobin concentrations of < 13 g/dl in males and < 12 g/dl in females to define anaemia, all but two (97%) of the patients were anaemic at some point during the study period. At weekly observations, the erythropoietic response of each patient with anaemia was categorized clinically, on the basis of absolute reticulocyte counts (ARC) and indirect bilirubin concentrations (IBC). At 4 weeks, 40 (56%) of the patients were still anaemic. The results of tests on samples of peripheral blood from these 40 patients were consistent with hypoproliferative erythropoiesis (low-normal ARC and IBC; 33 patients), ineffective erythropoiesis (low-normal ARC but elevated IBC; five patients) or an appropriate response (elevated ARC and normal IBC; two patients). Of the variables measured at the time of enrolment into the study, only low serum albumin (P = 0.002) and elevated direct bilirubin (P = 0.009) were independently associated with persisting anaemia at 4 weeks. Anaemia may therefore persist in about one in every two Thai patients for up to 28 days after beginning effective treatment for acute Plasmodium falciparum malaria, hypoproliferative erythropoiesis appearing to be the most common mechanism of this anaemia. While it is likely that the malarial episode itself is somehow responsible for these persistent haematological changes, other, underlying, chronic processes might have a contributory role. Whatever the cause, the continuing anaemia appears to be related to the degree of hepatic dysfunction on admission.
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PMID:The course of anaemia after the treatment of acute, falciparum malaria. 979 26

During the course of its development in the mosquito and transmission to a new vertebrate host, the malaria parasite must interact with the mosquito midgut and invade the gut epithelium. To investigate how the parasite recognizes the midgut before invasion, we have developed an in vitro adhesion assay based on combining fluorescently labelled ookinetes with isolated midgut epithelia from blood-fed mosquitoes. Using this assay, we found that Plasmodium gallinaceum ookinetes readily adhered to midguts of Aedes aegypti, mimicking the natural recognition of the epithelium by the parasite. This interaction is specific: the ookinetes preferentially adhered to the lumen (microvillar) side of the gut epithelium and did not bind to other mosquito tissues. Conversely, the binding was not due to a non-specific adhesive property of the midguts, because a variety of other cell types, including untransformed P. gallinaceum zygotes or macrogametes, did not show similar binding to the midguts. High concentrations of glycosylated (fetuin, orosomucoid, ovalbumin) or non-glycosylated (bovine serum albumin) proteins, added as non-specific competitors, failed to compete with the ookinetes in binding assays. We also found that the adhesion of ookinetes to the midgut surface is necessary for sporogonic development of the parasite in the mosquito. Antibodies and other reagents that blocked adhesion in vitro also reduced oocyst formation when these reagents were combined with mature ookinetes and fed to mosquitoes. Chemical modification of the midguts with sodium periodate at pH 5.5 destroyed adhesion, indicating that the ookinete binds to a carbohydrate ligand on the surface of the midgut. The ligand is sensitive to periodate concentrations of less than 1 mmol l-1, suggesting that it may contain sialic-acid-like sugars. Furthermore, free N-acetylneuraminic acid competed with the ookinetes in binding aasays, while other monosaccharides had no effect. However, in agreement with the current belief that adult insects do not contain sialic acids, we were unable to detect any sialic acids in mosquito midguts using the most sensitive HPLC-based fluorometric assay currently available. We postulate that a specific carbohydrate group is used by the ookinete to recognize the midgut epithelium and to attach to its surface. This is the first receptor-ligand interaction demonstrated for the ookinete stage of a malaria parasite. Further characterization of the midgut ligand and its parasite counterpart may lead to novel strategies of blocking oocyst development in the mosquito.
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PMID:Plasmodium gallinaceum ookinetes adhere specifically to the midgut epithelium of Aedes aegypti by interaction with a carbohydrate ligand. 992 52


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