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

The functional properties, regarding parasite growth inhibition in vitro, the cytotoxic potential and cytokine profiles of human gammadelta+ and alphabeta+ T cells, T-cell lines and clones stimulated with Plasmodium falciparum-antigen-or T-cell mitogen in vitro were investigated. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and specific primers, mRNA for the cytolytic molecules perforin, granzyme A and B, Fas and Fas ligand (FasL) were detected in both the gammadelta- and the alphabetaT cells. Despite this fact, only gammadeltaT cells inhibited, both Vdelta1+ and Vdelta2+, the in vitro growth of the asexual blood stages in a dose dependent manner. The inhibition required cell-to-cell contact and was not observed until the second parasite replication implied that the likely gammadeltaT-cell target was the extracellular merozoite or schizont. The failure of alphabetaT cells to inhibit the growth of the parasite suggests requirement of additional cytolytic molecules/signals or different receptor specificities exhibited by the gammadeltaT cells. Both the gammadelta- and alphabetaT cells expressed mRNA for a large number of cytokines. Interferon (IFN)-gamma, interleukin (IL) IL-5, IL-6, IL-8, tumour necrosis factor alpha (TNFalpha), tumour necrosis factor beta (TNF-beta)/lymphotoxin (LT) and T-cell growth factor beta-1 (TGF-beta1) were observed in all activated clones tested. No IL-3 was detected, while IL-1beta, IL-2, IL-4, IL-10 and GM-CSF were variably expressed. In conclusion, our data show that gammadeltaT cells in malaria nonimmune individuals inhibit the asexual blood stages of P. falciparum malaria, while similarly activated alphabetaT cells do not. Thus, it is likely that the gammadeltaT cells could play a mandatory role in the elimination of parasites and/or the regulation of the early immune response to malaria infection.
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PMID:Human gamma delta T cells that inhibit the in vitro growth of the asexual blood stages of the Plasmodium falciparum parasite express cytolytic and proinflammatory molecules. 1060 13

The polymorphic multigene family, var, encodes the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surface of erythrocytes infected with the human malaria parasite, P. falciparum. PfEMP1 has been implicated in the pathology of malaria through its ability to bind to host endothelial receptors and uninfected erythrocytes. Understanding the relationship between host pathology, immune response and parasite variation is crucial, but requires a method of reliably detecting and differentiating all possible var genes. Several primer pairs used to date are biased and limited in their detection capacity. Here we describe a set of PCR primers that amplify the majority of var genes in the laboratory isolates 3D7 and A4, and appear to work equally well on all isolates tested. We use these universal primers to examine the relationship between var gene transcription as assessed by reverse transcriptase-PCR (RT-PCR) with that measured by Northern analysis of parasite RNA. Phenotypically selected young parasites have multiple transcripts detected by RT-PCR, but the full-length transcript appears to be homogeneous. In addition, we demonstrate that the choice of primers used for RT-PCR is crucial in data interpretation.
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PMID:A study of var gene transcription in vitro using universal var gene primers. 1061 95

The role of neutrophils in experimental cerebral malaria (ECM) is not well understood. In this study we used a MoAb, RB6-8C5, to deplete the peripheral neutrophils of ECM-susceptible CBA/NSlc mice 24 h before Plasmodium berghei ANKA (PbA) infection. We found that early neutrophil depletion prevented the development of ECM and dramatically decreased the sequestration of monocytes and microhaemorrhage in the brain. The depletion of neutrophils also down-regulated tumour necrosis factor-alpha, interferon-gamma and IL-2 mRNAs and abrogated IL-12p40 mRNA expression in the brain as examined by competitive reverse transcriptase-polymerase chain reaction. Although depletion of neutrophils decreased the expression of Th1 cytokines in both spleen and brain, our results did not show the shift of a Th1 to a Th2 immune response since there was no obvious augmentation of expression of Th2 cytokine mRNAs (IL-4 and IL-10). We conclude that neutrophils play a role in the pathogenesis of ECM via enhancement of the expression of Th1 cytokines in the brain.
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PMID:Neutrophils play a critical role in the pathogenesis of experimental cerebral malaria. 1075 73

Some refractory anopheline mosquitoes are capable of killing Plasmodium, the causative agent of malaria, by melanotic encapsulation of invading ookinetes. Phenoloxidase (PO) appears to be involved in the formation of melanin and toxic metabolites in the surrounding capsule. A cDNA encoding Anopheles stephensi prophenoloxidase (Ans-proPO) was isolated from a cDNA library screened with an amplimer produced by reverse transcriptase polymerase chain reaction (RT-PCR) with degenerate primers designed against conserved proPO sequences. The 2.4-kb-long cDNA has a 2058 bp open reading frame encoding Ans-proPO of 686 amino acids. The deduced amino acid sequence shows significant homology to other insect proPO sequences especially at the two putative copper-binding domains. In A. stephensi, Ans-proPO expression was detected in larval, pupal and adult stages. The Ans-proPO mRNA was detected by RT-PCR and in situ hybridization in haemocytes, fat body and epidermis of adult female mosquitoes. A low level of expression was detected in the ovaries, whereas no expression was detected in the midguts. Semi-quantitative RT-PCR analysis of Ans-proPO mRNA showed that its expression was similar in adult female heads, thoraxes and abdomens. No change in the level of Ans-proPO expression was found in adult females after blood feeding, bacterial challenge or Plasmodium berghei infection. However, elevated PO activity was detected in P. berghei-infected mosquitoes, suggesting that in non-selected permissive mosquitoes PO may be involved in limiting parasite infection. Genomic Southern blot and immunoblots suggest the presence of more than one proPO gene in the A. stephensi genome, which is consistent with the findings in other Diptera and Lepidoptera species. The greatest similarity in sequence and expression profile between Ans-proPO and A. gambiae proPO6 suggests that they might be homologues. Our results demonstrate that Ans-proPO is constitutively expressed through different developmental stages and under different physiological conditions, implying that other factors in the proPO activation cascade regulate melanotic encapsulation.
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PMID:Molecular characterization of a prophenoloxidase cDNA from the malaria mosquito Anopheles stephensi. 1076 20

Jule is the second complete long-terminal-repeat (LTR) Ty3/Gypsy retrotransposon identified to date in vertebrates. Jule, first isolated from the poeciliid fish Xiphophorus maculatus, is 4.8 kb in length, is flanked by two 202-bp LTRs, and encodes Gag (structural core protein) and Pol (protease, reverse transcriptase, RNase H, and integrase, in that order) but no envelope. There are three to four copies of Jule per haploid genome in X. maculatus. Two of them are located in a subtelomeric region of the sex chromosomes, where they are associated with the Xmrk receptor tyrosine kinase genes, of which oncogenic versions are responsible for the formation of hereditary melanoma in Xiphophorus. One almost intact copy of Jule was found in the first intron of the X-chromosomal allele of the Xmrk proto-oncogene, and a second, more corrupted copy is present only 56 nt downstream of the polyadenylation signal of the Xmrk oncogene. Jule-related elements were detected by Southern blot hybridization with less than 10 copies per haploid genome in numerous other poeciliids, as well as in more divergent fishes, including the medakafish Oryzias latipes and the tilapia Oreochromis niloticus. Database searches also identified Jule-related sequences in the zebrafish Danio rerio and in both genome project pufferfishes, Fugu rubripes and Tetraodon nigroviridis. Phylogenetic analysis revealed that Jule is the first member of the Mag family of Ty3/Gypsy retrotransposons described to date in vertebrates. This family includes the silkworm Mag and sea urchin SURL retrotransposons, as well as sequences from the nematode Caenorhabditis elegans. Additional related elements were identified in the genomes of the malaria mosquito Anopheles gambiae and the nematode Ascaris lumbricoides. Phylogeny of Mag-related elements suggested that the Mag family of retrotransposons is polyphyletic and is constituted of several ancient lineages that diverged before their host genomes more than 600 MYA.
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PMID:Jule from the fish Xiphophorus is the first complete vertebrate Ty3/Gypsy retrotransposon from the Mag family. 1115 69

We have characterized brain cytokine expression profiles in the Plasmodium coatneyi/rhesus (Macaque mulatta) malaria model. Eight rhesus monkeys were included in the study; four were infected with P. coatneyi, and four were used as uninfected controls. All inoculated animals became infected. Eleven days after parasite inoculation, the rhesus monkeys were killed and tissue samples from 4 regions of the brain (cortex and white matter of the cerebrum, cerebellum, and midbrain) were collected for quantitation of mRNA expression of cytokines, adhesion molecules, and inducible nitric oxide synthetase (iNOS) by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression levels of tumor necrosis actor-alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-1-beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synethetase (iNOS) were highest in the cerebellum of infected animals, correlating well with pathologic observations of sequestration of parasitized erythrocytes in this region of the brain. Infected animals also had higher TNF-alpha expression levels in the cortex and IL-1beta expression levels in the cortex, white matter, and midbrain. Thus, the expression of pro-inflammatory and T helper-1 (TH-1) cytokines, adhesion molecules, and iNOS appears to predominate in the cerebellum of infected rhesus monkeys.
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PMID:Expression of proinflammatory cytokines in four regions of the brain in Macaque mulatta (rhesus) monkeys infected with Plasmodium coatneyi. 1122 Jul 73

Database analysis revealed a novel family of very short interspersed repetitive elements named Maque in the African malaria mosquito, Anopheles gambiae. Past mobility of Maque was demonstrated by evidence of its insertion that resulted in a target duplication. Approximately 220 copies of Maque were present in the A. gambiae genome. Although only approximately 60 bp long, Maque has the appearance of a distinct transposition unit. Eleven of the 12 Maque elements found in the database were flanked by 9-14 bp direct repeats, indicating that their transposition was relatively recent. Sequence comparison and phylogenetic analyses suggest that there are at least two subgroups within the Maque family, suggesting that they may have been originated from more than one source. Five of the 12 Maque elements had at least one other repetitive element nearby. Three of the Maque elements were found near genes. However, Maque was not found in the coding regions of genes or in any of the expressed sequence tags (ESTs), which is consistent with its significantly biased distribution toward A + T rich regions. Several characteristics of Maque indicate that it is likely a non-autonomous retro-element. The evolutionary origin of Maque and the differences between Maque and other known retro-elements including short interspersed repetitive elements (SINEs) are discussed. A hypothesis is proposed in which short sequences containing just the reverse transcriptase recognition signal (RTRS) could potentially contribute to exon shuffling and the genesis of some primordial SINEs.
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PMID:Maque, a family of extremely short interspersed repetitive elements: characterization, possible mechanism of transposition, and evolutionary implications. 1122 64

Molecular studies of insect disease vectors are of paramount importance for understanding parasite-vector relationship. Advances in this area have led to important findings regarding changes in vectors' physiology upon blood feeding and parasite infection. Mechanisms for interfering with the vectorial capacity of insects responsible for the transmission of diseases such as malaria, Chagas disease and dengue fever are being devised with the ultimate goal of developing transgenic insects. A primary necessity for this goal is information on gene expression and control in the target insect. Our group is investigating molecular aspects of the interaction between Leishmania parasites and Lutzomyia sand flies. As an initial step in our studies we have used random sequencing of cDNA clones from two expression libraries made from head/thorax and abdomen of sugar fed L. longipalpis for the identification of expressed sequence tags (EST). We applied differential display reverse transcriptase-PCR and randomly amplified polymorphic DNA-PCR to characterize differentially expressed mRNA from sugar and blood fed insects, and, in one case, from a L. (V.) braziliensis-infected L. longipalpis. We identified 37 cDNAs that have shown homology to known sequences from GeneBank. Of these, 32 cDNAs code for constitutive proteins such as zinc finger protein, glutamine synthetase, G binding protein, ubiquitin conjugating enzyme. Three are putative differentially expressed cDNAs from blood fed and Leishmania-infected midgut, a chitinase, a V-ATPase and a MAP kinase. Finally, two sequences are homologous to Drosophila melanogaster gene products recently discovered through the Drosophila genome initiative.
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PMID:Characterization of constitutive and putative differentially expressed mRNAs by means of expressed sequence tags, differential display reverse transcriptase-PCR and randomly amplified polymorphic DNA-PCR from the sand fly vector Lutzomyia longipalpis. 1128 81

In a serendipitous result, pharmacophores generated for the database searching for new non-nucleoside inhibitors of the HIV-1 reverse transcriptase enzyme unearthed 12 new lead compounds which were active against the Plasmodium falciparum strain of malaria.
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PMID:New anti-malarial compounds from database searching. 1184 67

With the Plasmodium falciparum genome sequencing near completion, functional analysis of individual parasite genes has become the major task of the postgenomic era. Understanding the expression patterns of individual genes is the initial step toward this goal. In this report, we have examined gene expression during gametocytogenesis of the malaria parasite, P. falciparum, using a modified differential display (DD) method. The modifications of this method include adjusting the dNTP mix, using upstream primers with higher AT contents, and reducing the extension temperature of the polymerase chain reaction (PCR). With a combination of 16 arbitrary upstream primers and 3 one-base-anchored oligo(dT) primers, we have successfully cloned 80 unique cDNA tags from stage IV-V gametocytes. Further analysis by dot blots and semiquantitative reverse transcriptase-PCR showed that at least 49 cDNAs had induced or elevated levels of expression in gametocytes. These results indicate that this modified DD procedure is suitable for large-scale identification of developmentally regulated genes in the AT-rich Plasmodium genome.
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PMID:Plasmodium falciparum: differential display analysis of gene expression during gametocytogenesis. 1188 52


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