Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 reverse transcriptase-polymerase chain reaction (RT-PCR) was used to amplify selected lymphokine mRNAs from phytohemagglutinin-activated leukocytes of the owl monkey (Aotus trivirgatus). Interleukin-2 (IL-2), IL-4, IL-13, and interferon-gamma were selected as lymphokine mRNAs of interest, since expression of these cytokines helps define the type of T helper lymphocyte response (i.e., TH1 versus TH2). Because sequences for these lymphokine genes were not available for the owl monkey, multiple PCR primers for each lymphokine gene were designed based on published human sequences. Various PCR primer pairs were then used in the RT-PCR to determine the conditions for optimal amplification of each owl monkey cytokine mRNA. In addition, each PCR primer pair was compared for the ability to amplify lymphokine mRNAs from other primate species, including African green (Cercopithecus aethiops), squirrel (Saimiri sciureus), and rhesus (Macaca mulatta) monkeys. The specificity and sensitivity of optimal primer pair was also demonstrated by amplification of as little as 10 fg of each lymphokine gene in a background of 300 ng of irrelevant cDNA. Finally, partial sequences of owl monkey coding regions for IL-2, IL-13, and interferon-gamma were determined and compared for homology with their human counterparts. Together, these studies define specific and sensitive conditions for detection of lymphokine mRNA expression in the owl monkey and provide partial sequence information of the coding region for these lymphokines. This investigation should provide molecular probes to investigate the immune response against malaria and the effectiveness of malaria vaccines in the owl monkey that models this human disease.
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PMID:Reverse transcriptase-polymerase chain reaction amplification and partial sequence of T helper 1- and T helper 2-type lymphokine genes from the owl monkey (Aotus trivirgatus). 912 42

Infants born in areas of stable malaria transmission are relatively protected against severe morbidity and high density Plasmodium falciparum blood-stage infection. This protection may involve prenatal sensitization and immunologic reactivity to malaria surface ligands that participate in invasion of red cells. We examined cord blood T and B cell immunity to P. falciparum merozoite surface protein-1 (MSP-1) in infants born in an area of stable malaria transmission in Kenya. T cell cytokine responses to the C-terminal 19-kDa fragment of MSP-1 (MSP-1(19)) were detected in 24 of 92 (26%) newborns (4-192 IFN-gamma and 3-88 IL-4-secreting cells per 10(6)/cord blood lymphocytes). Peptide epitopes in the N-terminal block 3 region of MSP-1 also drove IFN-gamma and/or IL-13 production. There was no evidence of prenatal T cell sensitization to liver-stage Ag-1. A total of 5 of 86 (6%) newborns had cord blood anti-MSP-1(19) IgM Abs, an Ig isotype that does not cross the placenta and is therefore of fetal origin. The frequency of neonatal B cell sensitization was higher than that indicated by serology alone, as 5 of 27 (18%) cord blood samples contained B cells that produced IgG when stimulated with MSP-1(19) in vitro. Neonatal B cell IgG responses were restricted to the Q-KNG allele of MSP-1(19), the major variant in this endemic area, whereas T cells responded to all four MSP-1(19) alleles evaluated. In utero sensitization to MSP-1 correlated with the presence of malaria parasites in cord blood (chi(2) = 20, p < 0.0001). These data indicate that prenatal sensitization to blood-stage Ags occurs in infants born in malaria endemic areas.
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PMID:Acquired immune responses to Plasmodium falciparum merozoite surface protein-1 in the human fetus. 1175 81

Collaborative studies have identified some genetic factors contributing to the development of severe forms of malaria and schistosomiasis. In Thailand, the TNF-alpha 5'-flanking region shows biallelic polymorphic sites at nucleotides -238, -308, -857, -863, and -1031, and seven alleles have been identified in patients from Myanmar. We found that the TNF promoter (TNFP)-D allele was significantly associated with cerebral malaria in populations from Karen (P < 0.0001, OR = 124.86) and ethnic Burma (P < 0.0001, OR = 34.50). In China, we have identified two major genes related to the severity of liver fibrosis, one an HLA class II gene, and the other the IL-13 gene. The frequency of the HLA-DRB5*0101 allele and that of the IL-13 promoter A/A (IL-13P- A/A) genotype were elevated in fibrotic patients, although the two genes are located on different chromosomes, chromosomes 6p and 5q, respectively. Subjects with both genotypes had odds ratios (OR = 24.5) much higher than the sum of the ratios for each individual genotype (OR = 5.1, 95% Confidence Interval 1.3-24.7 for HLA-DRB5*0101, OR = 3.1 95% CI 1.5 - 6.5 for IL-13P- A/A). That the effects of the two susceptibility markers are synergistic rather than additive, strongly suggests that the pathogenic Th2 response directly influences the prognosis of post-schistosomal liver fibrosis.
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PMID:Genetic factors associated with development of cerebral malaria and fibrotic schistosomiasis. 1250 99

The effects of exposure to placental malaria infection on newborn immunological responses, in particular Th1/Th2 cytokines and antigen-presenting cell (APC) function, were compared between cord blood mononuclear cells (CBMC) from parasitized and non-parasitized placentas of Gambian women. Cells were analysed in vitro for their ability to respond to mitogens [phorbol myristate acetate (PMA)/ionomycin, phytohaemagglutinin (PHA)], a malaria-unrelated test antigen [purified protein derivative of Mycobacterium tuberculin[purified protein derivative (PPD)] and Plasmodium falciparum schizont extracts. Mitogens induced strong proliferation and secretion of high concentrations of both IL-13 and sCD30 in CBMC from both groups. Conversely, significantly lower amounts of IFN-gamma were induced in the parasitized group in response to low doses of PHA. Protein antigens induced very low amounts of all tested cytokines, in particular IFN-gamma. However, a significantly higher release of sCD30 was observed in response to schizont extracts in the parasitized group. Addition of LPS to activate APC to low doses of PHA or schizont extracts increased the IFN-gamma production in both groups but levels remained lower in CBMC from the parasitized group. This result correlates with the lower production of IL-12 found following lipopolysaccharide (LPS) stimulation in this group. Taken together, these data show that placental infection with P. falciparum affects Th1 differentiation and sCD30 priming of neonatal lymphocytes and that the probable mode of action is via APC.
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PMID:Plasmodium falciparum infection of the placenta affects newborn immune responses. 1293 Mar 69

We examined a possible association of single-nucleotide polymorphisms (SNPs) in the promoters of IL-3, IL-4, and IL-13 genes on the 5q31-33, IL-3 -16T>C, IL-4 -590T>C, and IL-13 -1055C>T, with severity of malaria in 361 adult malaria patients in Thailand. The IL-13 -1055T allele showed a significant association with protection from severe malaria (OR 0.51, 95% CI 0.32-0.80; P=0.0032 by the chi(2) test), while allele frequencies of IL-3 -16T>C and IL-4 -590T>C were not statistically different between mild and severe malaria patients. An IL-13 -1055C>T has been reported to alter the regulation of IL-13 production. Thus, IL-13 -1055T may show resistance to severe malaria through the alteration of IL-13 production.
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PMID:A single-nucleotide substitution from C to T at position -1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand. 1455 8

BALB/c interleukin-4 (IL-4(-/-)) or IL-4 receptor-alpha (IL-4ralpha(-/-)) knockout (KO) mice were used to assess the roles of the IL-4 and IL-13 pathways during infections with the blood or liver stages of plasmodium in murine malaria. Intraperitoneal infection with the blood-stage erythrocytes of Plasmodium berghei (ANKA) resulted in 100% mortality within 24 days in BALB/c mice, as well as in the mutant mouse strains. However, when infected intravenously with the sporozoite liver stage, 60 to 80% of IL-4(-/-) and IL-4ralpha(-/-) mice survived, whereas all BALB/c mice succumbed with high parasitemia. Compared to infected BALB/c controls, the surviving KO mice showed increased NK cell numbers and expression of inducible nitric oxide synthase (iNOS) in the liver and were able to eliminate parasites early during infection. In vivo blockade of NO resulted in 100% mortality of sporozoite-infected KO mice. In vivo depletion of NK cells also resulted in 80 to 100% mortality, with a significant reduction in gamma interferon (IFN-gamma) production in the liver. These results suggest that IFN-gamma-producing NK cells are critical in host resistance against the sporozoite liver stage by inducing NO production, an effective killing effector molecule against Plasmodium. The absence of IL-4-mediated functions increases the protective innate immune mechanism identified above, which results in immunity against P. berghei infection in these mice, with no major role for IL-13.
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PMID:Mice deficient in interleukin-4 (IL-4) or IL-4 receptor alpha have higher resistance to sporozoite infection with Plasmodium berghei (ANKA) than do naive wild-type mice. 1468 11

Interleukin-18 (IL-18) is a potent proinflammatory cytokine that induces interferon-gamma (IFN-gamma) production from Th1 cells, NK cells and activated macrophages, particularly in the presence of IL-12. However, it is also shown that without help from IL-12, IL-18 is capable of inducing IL-4 and IL-13 production in T cells, NK cells, mast cells and basophils, and that administration of IL-18 in conjunction with an allergen increases serum IgE levels. In order to clarify the role of IL-18 in disease severity of falciparum malaria, we have examined serum levels of IL-18, IFN-gamma, and IgE for 96 patients with falciparum malaria [Trans. R. Soc. Trop. Med. Hyg. 97, 236-241]. Results suggested that IL-18 plays a key role in inducing severe malaria through a pathway of elevating IFN-gamma, rather than its IgE inducing activity. Based on these results, the role of IL-18 in severe falciparum malaria will be discussed in this review.
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PMID:A potential role of interleukin 18 in severe falciparum malaria. 1474 54

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 166Ho-DOTMP 5A8; A-179578, abetimus sodium, adefovir dipivoxil, AGI-1067, AIDSVAX gp120 B/B, AK-602, alefacept alemtuzumab, aliskiren fumarate, ALVAC vCP1433, ALVAC vCP1452, anecortave acetate, arzoxifene hydrochloride, atazanavir sulfate, atlizumab, avasimibe; Binodenoson, BMS-488043; Choriogonadotropin alfa, ciclesonide, COL-1621, CVT-3146, CVT-E002, Cypher; Daptomycin, darbepoetin alfa, darunavir, D-D4FC, deferasirox, desloratadine, desmoteplase, duloxetine hydrochloride, DX-9065a; E-5564, efalizumab, emfilermin, emivirine, emtricitabine, enfuvirtide, estradiol acetate, ezetimibe; Frovatriptan; Gallium maltolate, gefitinib; HIV-1 Immunogen, human insulin; Iguratimod, IL-4/IL-13 Trap, imatinib mesylate, inhaled insulin, insulin glargine, irofulven, ISS-1018, ivabradine hydrochloride; Lutropin alfa; Melatonin; Nesiritide; O6-Benzylguanine, omapatrilat, oritavancin, ospemifene; Parecoxib sodium, peginterferon alfa-2a, pexelizumab, pimecrolimus, pirfenidone, pramlintide acetate, prasterone sulfate PT-141; Rasburicase, razaxaban hydrochloride, recombinant malaria vaccine, rhBMP-2/ACS, roflumilast, rosiglitazone maleate/metformin hydrochloride, rotavirus vaccine; SCH-D, sitaxsentan sodium, solifenacin succinate; Targinine hydrochloride, taxus, TER-199, tramadol hydrochloride/acetaminophen; Valdecoxib, valganciclovir hydrochloride, vatalanib succinate, VEG Trap(R1R2); Ximelagatran; Yttrium Y90 Epratuzumab.
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PMID:Gateways to clinical trials. 1531 8

The frequency of P. falciparum-specific interleukin (IL)-2-, interferon (IFN)-gamma-, tumor necrosis factor (TNF)-alpha- and IL-10-expressing CD3+ cells was studied in healthy Gabonese children segregated according to their clinical presentation at admission to a longitudinal study of severe and mild malaria. The percentage of IL-2- and TNF-alpha- expressing P. falciparum-specific CD3+ cells was significantly higher in the children with prior mild malaria and less frequent reinfections compared to the children with prior severe malaria and more frequent reinfections. No differences were shown for P. falciparum-specific IFN-gamma and IL-10 expression within CD3+ cells and parasite-non-specific expression of IL-2, IL-4, IL-6, IL-10, IL-13, TNF-alpha, and IFN-gamma within the CD4+, CD8+, TCRgamma\delta+ CD3+ and CD94+ CD3- cell populations, indicating that immunological determinants regulating the susceptibility to malaria in age-matched children are parasite-specific. The ability of P. falciparum-specific T cells to mount a rapid IL-2 and TNF-alpha response might be of significance in preventing severe disease and reinfection.
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PMID:Plasmodium falciparum-specific interleukin-2 and tumor necrosis factor-alpha expressing-T cells are associated with resistance to reinfection and severe malaria in healthy African children. 1554 42

Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.
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PMID:Distinct Th1- and Th2-Type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands. 1590 75


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