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)

A/J and CBA/H mice infected with Plasmodium berghei ANKA, a murine model of cerebral malaria, were used to see whether antioxidants influenced the outcome of this disease. Untreated, infected mice died 7 to 9 days after infection, often with cerebral symptoms. Haemorrhages, mononuclear infiltration and oedema were present in the central nervous system (CNS). Feeding a diet containing 0.75% (w/w) butylated hydroxyanisole (BHA) greatly altered the course of this disease. Death was delayed by up to 2 weeks and mice appeared healthy at parasitaemias that would have caused cerebral symptoms and death had they been on a conventional diet. BHA-fed mice showed few or no cerebral symptoms at a time at which control mice were clearly affected, and greatly reduced haemorrhages, mononuclear infiltration and oedema when the CNS was examined. Similar, but more consistent, protective effects were seen after administration of BHA by repeated injections or in osmotic pumps. The combination of superoxide dismutase and catalase, coupled to polyethylene glycol, when administered intravenously also protected mice against death from cerebral complications. Permeability of the blood-brain barrier was monitored by the use of 125I-labelled bovine serum albumin, 51Cr-labelled erythrocytes and the dye Evans blue, all of which are normally excluded from the CNS. Infected mice on control diet showed an increase in Evans blue staining and 125I and 51Cr retention in the CNS tissue itself. Feeding the diet containing BHA reduced these indices of increased blood-brain barrier permeability. In view of the potent radical scavenging activity of BHA in many other systems it is likely, but unproven, that this is its main role here. The protective effect of superoxide dismutase and catalase lends support to the idea that reactive oxygen species are involved in the pathology of experimental cerebral malaria.
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PMID:Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. 266 24

Chloroquine phosphate (CP) has been formulated in a suppository base consisting of polyethylene glycol, PEG 1000 and PEG 6000 (7:3) with 0.5% polysorbate 80 included as an absorption promoter. Peak chloroquine blood levels in children (mean body weight 10 kg, age 21 months) were 0.67 +/- 0.08 micrograms/ml (after 200 mg CP) and 1.06 +/- 0.23 micrograms/ml (after 300 mg CP) following rectal administration of the suppositories. Prior to drug administration, the base level chloroquine was 0.30 +/- 0.02 micrograms/ml. Elimination half lives calculated from the rapid phase of log concentration-time curves were 3.3 h (after 200 mg CP) and 2.7 h (after 300 mg CP), respectively. Based on literature evidence the blood levels obtained with the 300 mg CP suppositories would be therapeutic in the management of malaria and rheumatoid disease.
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PMID:Chloroquine absorption in children from polyethylene glycol base suppositories. 320 29

Immune complexes have been partially purified from the serum of Plasmodium berghei-infected mice by ultracentrifugation on 10 to 40% linear sucrose gradients, by precipitation with polyethylene glycol, and by gel filtration through Sephacryl S-300. The complexes contain gamma 1, gamma 2a, gamma 2b, and gamma 3 subclasses of mouse immunoglobulin G in differing amounts, as well as malarial antigen. Complexes isolated by all three methods inhibit Fc receptor-mediated phagocytosis by normal mouse peritoneal macrophages but do not inhibit attachment to the Fc receptor or to the C3 receptor or the ingestion of latex particles. The phagocytosis-inhibiting activity of the immune complexes can be partially removed by prior incubation with protein A-Sepharose CL-4B. Splenic macrophages, isolated from P. berghei-infected mice, may be already coated with immune complexes in vivo. Attachment of mouse erythrocytes sensitized with immunoglobulin G to these macrophages is greatly enhanced during malaria, but ingestion is not. These results suggest that immune complexes modulate the immune response to malaria by inhibiting immune phagocytosis and perhaps by interfering with other effector mechanisms. Further understanding of the influence of immune complexes and the antigens involved in these complexes may be useful in vaccine development and prophylaxis.
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PMID:Murine malaria: immune complexes inhibit Fc receptor-mediated phagocytosis. 636 90

Mouse myeloma cells were fused with blood stage forms of the rodent malaria parasite Plasmodium chabaudi and with promastigotes of Leishmania donovani, the causative agent of kala-azar in man. The fusion was carried out by polyethylene glycol treatment. The parasites provided the enzyme which enabled the hybrids to grow in selective medium containing aminopterin. Clones of parasite-myeloma hybrids grown in continuous culture for up to 5 months expressed parasite antigen and induced anti-parasite antibodies in mice.
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PMID:Production of hybrids of mouse myeloma cells and protozoa which express parasite antigens. 637 72

Plasmodium berghei-infected mouse red cells have enhanced fusion capacity as triggered by addition of poly(ethylene glycol) in the presence of Ca2+. The uptake of Ca2+ in P. berghei-infected cells is greater than in normal cells, and the difference in Ca2+ uptake was found to be enhanced in the presence of poly(ethylene glycol). Fusion of normal and P. berghei-infected red cells by poly(ethylene glycol) was significantly inhibited by N-tosyl-L-lysylchloromethyl ketone and phenylmethylsulphonyl fluoride. In addition, ethyleneglycolbis(aminoethylether)tetra-acetate, N-ethylmaleimide, iodoacetamide, cystamine and tetrathionate also prevented fusion in both systems. In contrast, N-tosyl-L-phenylalanylchloromethyl ketone and N-tosyl-L-arginine methyl ester did not inhibit cell fusion. The latter enhanced fusion of infected cells but was without effect on normal cells. These results indicate that a Ca2+-activated thiol proteinase may be involved in membrane fusion in malaria-infected as well as in normal red cells. However, differences in the effect of proteinase inhibitors and substrate on fusion and Ca2+ entry show that the processes leading to fusion may not be identical.
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PMID:Mechanism of enhanced fusion capacity of mouse red cells infected with Plasmodium berghei. 641 72

Immunoglobulin-lipoprotein complexes have been investigated in the course of P. chabaudi acute infection of Swiss mice. Serum ultracentrifugation in a sucrose density gradient was used to demonstrate the presence of immunoglobulins in the enriched lipoprotein fraction of density lower than 1100. The levels of lipoprotein-bound immunoglobulins (Ig-Lp) were measured using the rate-nephelometric Immuno-Chemistry-System. IgM-Lp and IgG-Lp were significantly increased at day 9 and reached a peak at day 13 post-infection. From day 13 to day 16 they dramatically decreased. This kinetic effect was similar to that of non-specific circulating immune complexes detected by the [125I]Clq binding assay. A radioimmuno-precipitation-PEG-assay (RIPEGAssay) with [125I]Lp revealed the highest Lp precipitation with day 13 post-infection mouse sera compared to controls. Similar results were recorded when control sera were 8 times as concentrated in order to obtain Ig levels identical in both control and experimental sera. Part of the lipoprotein-bound immunoglobulins were demonstrated to be anti-Lp antibodies by the way of the RIPEGAssay using F(ab')2 fragments from infected mouse sera. Moreover, the [125I]Clq bound to the Ig-Lp complexes isolated from day 13 mouse sera. The present data suggest that the alteration of lipid metabolism which characterizes malaria infection could lead to the complexation of lipoproteins to immunoglobulins.
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PMID:[Immunoglobulin-lipoprotein complexes during P. chabaudi infection]. 675 74

The capacity of normal and malaria-infected mouse red cells to undergo fusion was investigated by phase contrast microscopy. The fusion of mouse red cells induced by 50% w/w poly(ethylene glycol)-6000 in the presence of Ca+2 is enhanced by P. berghei infection. Cells carrying parasites in the ring form stage and early trophozoite stage show slightly higher fusion induced by dimethyl sulphoxide and Ca+2 than those carrying parasites in trophozoite and schizont stages.
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PMID:Enhanced fusion capacity of malaria (Plasmodium berghei)-infected mouse red cells. 699 73

Immobilized metal-ion affinity partitioning (IMAP) is shown to be useful as a preliminary screening test and for the separation of different cell populations based upon recognition of the differences in the proteins on cell surfaces. The feasibility of using IMAP to segregate a spectrum of normal human cells (red blood cells, lymphocytes and fibroblasts) from their counterpart pathological cells has been demonstrated. A clear segregation between normal and sickle-cell anemia red blood cells (RBC), or malaria (Plasmodium vivax) infected RBCs was obtained. Further, the partition differences were found to depend on the nature and the concentrations of metal used. Cells from breast cancer and those from the lung adenocarcinoma showed differences in their partition pattern as compared to normal fibroblasts when PEG-IDA-M(II) was added to the phase system. Maximum differences between the three cell populations were observed in the presence of 10% PEG-IDA-Ni(II). Normal lymphocytes and Burkitt's lymphoma cells (Raji and Namalwa cell lines) were shown to partition differently in the presence of PEG-IDA-M(II) in the phase system. Normal lymphocytes could be distinguished from the Burkitt's lymphoma cell lines in all three phases (top, interface and bottom), in the presence of 10% PEG-IDA-Ni(II) in the system. These differences in the partition behavior could mainly be attributed to the density, surface exposure and micro-environment of histidine residues of cell membrane-associated proteins. These data, along with those obtained for normal and pathological human cells show that IMAP could be a simple and versatile tool for the segregation and study of cells.
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PMID:Segregation of normal and pathological human red blood cells, lymphocytes and fibroblasts by immobilized metal-ion affinity partitioning. 759 55

ELISA is widely used as a means to detect antibodies, but the potential of ELISA plates as an immunosorbent for the purification of specific antibodies does not seem to have been evaluated. In this study, ELISA plates coated with peptides representing short sequences of various antigens from Plasmodium falciparum, the etiologic agent of human malaria, have been successfully used as a means to purify small amounts of the corresponding antibodies. ELISA plates, identical to those used for antibody detection, also permitted the evaluation of various elution conditions for each pairing of peptide and serum; we tested four eluting buffers (0.2 M glycine, pH 2.5; 0.2 M lysine, pH 11.5; 3.0 M MgCl2, 0.075 M Hepes, 25% ethylene glycol, pH 7.1-7.2 and 4 M NH4SCN in 0.1 M NaH2PO4, pH 6.0) with four pairs of peptides and sera. The ELISA plates could also be used to estimate the affinity of the eluted antibodies by the technique of Pullen et al. (1986). The eluted antibodies were compared to those obtained by immunopurification on recombinant proteins adsorbed on nitrocellulose filters. In contrast to the latter, they were not contaminated by antibodies directed against the carrier moiety of the recombinant protein. When used in immunofluorescence assays with various stages of the parasite the antibodies immunopurified on peptides bound to ELISA plates were able to react with the native antigens in the parasite.
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PMID:Fast immunopurification of small amounts of specific antibodies on peptides bound to ELISA plates. 850 53

An immunogenic and tolerogenic characterisation of monomethoxypoly(ethylene glycol) conjugated proteins was carried out using, as immunogen models, an anti-malaria chimera monoclonal antibody (PfChMab) and a macrophage colony stimulating factor (M-CSF). Two conjugates of PfChMab were prepared by polymer derivatisation of 19 and 33% protein amino groups and one conjugate of M-CSF was obtained by modification of 24% amino groups. In mice M-CSF was found to elicit rapidly high IgG and IgM levels whereas the monomethoxypoly(ethylene glycol) derivatised M-CSF stimulated a significantly lower immunoresponse. Native PfChMab was found to induce a delayed immunoresponse with high IgM levels but low production of IgG. Furthermore, similar immunogenic profiles were obtained with the native and modified protein forms. The pre-administration of polymer conjugated M-CSF to mice subsequently treated with the native protein was found to suppress up to 75% of anti-native M-CSF IgG, while IgM production was not affected. On the other hand the pre-administration of monomethoxypoly(ethylene glycol) derivatised PfChMab was found to reduce significantly the generation of anti-native PfChMab IgM. Such suppression depended on the degree of modification: the conjugate with the higher number of polymer chains was more effective in suppressing the immunoresponse.
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PMID:Immunogenic and tolerogenic properties of monomethoxypoly(ethylene glycol) conjugated proteins. 1048 10


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