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 subunit vaccine for Plasmodium falciparum malaria will need to contain well-defined T helper cell epitopes that induce protective immune responses to the parasite. One major barrier to the use of subunit vaccines is the requirement for T helper cell epitopes to be presented by the HLA class II molecules that are present in the population being vaccinated. Since the majority of malaria studies have focused on HLA-DR, little information on the role of HLA-DQ in the binding and immune response to malarial epitopes is available. This study used an in vitro peptide-binding assay to predict the extent of HLA-DQ binding of four conserved T helper cell epitopes identified from asexual-stage malaria vaccine candidate antigens. Epstein-Barr virus (EBV)-transformed human B-cell lines expressing 14 different DQ molecules (DQ2.1, -2.2, -4.1, -4.2, -5.1 to -5.3, -6.1, -6.2, -6.4, -7.1, -7.3, -8, and -9) representing all broad serological specificities, including common DQ molecules present in populations in areas where malaria is endemic, were used in the binding assay. Moreover, an HLA-DQ transgenic mouse model was employed to evaluate the correlation between the in vitro DQ binding of the peptides and the generation of in vivo immune responses following peptide immunization. This study identified two broad DQ-binding peptides, ABRA#14 and SERA#9. ABRA#14 also induced T-cell proliferation and Th1-associated cytokine production in DQ8(+) transgenic mice. The combination of peptide binding to EBV-transformed cell lines and DQ transgenic mice provides a method for identifying additional T-cell epitopes for inclusion in a vaccine.
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PMID:Assessing the binding of four Plasmodium falciparum T helper cell epitopes to HLA-DQ and induction of T-cell responses in HLA-DQ transgenic mice. 1067 49

Burkitt's lymphoma has the highest incidence of any childhood cancer in equatorial Africa. Geographic distribution appears to be related to climatic conditions and coincides with areas of endemic malaria. These tumors are characterized by reciprocal translocation from chromosome 8 at or near the c-myc locus to either the immunoglobulin chain locus on chromosome 14 (80 p. 100 of cases) or one of the light chain loci on chromosome 2 or 22. As a result of this translocation, transcription of the protooncogene c-myc is activated. Deregulation of c-myc could play a major role in onset and development of the tumor. Study of Burkitt's lymphoma led to the discovery of the first association between viral infection and tumor development in humans. The Epstein-Barr virus is contained in all endemic Burkitt's lymphoma cells, thus implicating it as a likely etiologic factor. Viral expression is reduced essentially to small non-coding RNA, non-polyadenilates, and EBERs (10(6) copies per cell) and a nuclear protein EBNA1 which is indispensable for maintenance of the Epstein-Barr virus genome in infected cells. Expression of EBNA in transgenes leads to lymphoma in mice and could play a role in the expression of the c-myc gene involved in translocations.
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PMID:[Epstein-Barr virus and Burkitt's lymphoma]. 1090 54

Intermittent fever is rare during the course of infectious diseases but it represents a diagnostic and therapeutic challenge. The most frequent infectious causes of intermittent fever are focal bacterial infections, mainly infections localised to canals like urinary or biliary ducts or the colon and also infections of a foreign material. Other causes are less frequent, like infective endocarditis, tuberculosis, infections due to Yersinia enterocolitica or malaria, or exceptional like borreliosis, ratbite fever, chronic meningococcemia or chronic Epstein-Barr Virus infection. Careful anamnesis and clinical examination as well as a few simple complementary investigations, preferably performed during a febrile episode, are often sufficient to set the limits of possible further more complex investigations.
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PMID:[Intermittent fever of infectious origin]. 1191 56

Burkitt's lymphoma is the commonest childhood malignancy in tropical Africa and the predisposing factors include malaria and infection with the Epstein-Barr virus. Recent studies suggest that the prevalence of this neoplasm is declining in this environment. The present study was undertaken to investigate whether there is a real decrease in the occurrence of Burkitt's lymphoma. We analysed 665 cases of childhood malignancies reported in the Ibadan Cancer Registry between 1991 and 1999. Burkitt's lymphoma and retinoblastoma remained the two commonest specific childhood malignancies, accounting for 19.4% and 17.9% of all childhood cancers, respectively. However, this represents a significant decline in the relative frequency of Burkitt's lymphoma when compared with similar surveys for the periods 1960 to 1972 and 1973 to 1990 when Burkitt's lymphoma accounted for 51.5% and 37.1%, respectively, of all childhood malignancies. In Ibadan, it seems that what appeared to be minor changes might actually be a real decline in the incidence of Burkitt's lymphoma and that it might be partly ascribed to improved living conditions and greater control of malaria.
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PMID:Decline in the frequency of Burkitt's lymphoma relative to other childhood malignancies in Ibadan, Nigeria. 1207 Sep 51

Vaccines against a number of diseases, including HIV, Epstein Barr virus, malaria and several cancers, are believed to require the coinduction of multiple alphabeta CD8+ cytotoxic T-lymphocyte responses that are directed towards a number of different target antigens. The difficulties associated with making large recombinant vaccines that contain numerous antigens has led to the development of alphabeta CD8+ cytotoxic T-lymphocyte polyepitope or polytope vaccine approach, where multiple (usually 8-10 amino acids long) alphabeta CD8+ cytotoxic T-lymphocyte epitopes, derived from several antigens are conjoined into single artificial constructs. Such polytope constructs can be delivered using a number of different vaccine vector modalities with each epitope in the construct emerging as individually immunogenic.
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PMID:Polytope vaccines for the codelivery of multiple CD8 T-cell epitopes. 1290 59

We report on the characteristics of 21 patients with hepatosplenic gammadelta T-cell lymphoma (HSgammadeltaTCL), an entity recognized since 1994 in the Revised European American Lymphoma (REAL) classification. Median age was 34 years. Patients had splenomegaly (n = 21), hepatomegaly (n = 15), and thrombocytopenia (n = 20). Histopathologic findings were homogeneous and showed the presence of medium-sized lymphoma cells within the sinusoids of splenic red pulp, liver, and bone marrow. Marrow involvement was usually mild but could be demonstrated by phenotyping in all patients. Cells were CD3+CD5-, expressed the gammadelta T-cell receptor, and had a nonactivated cytotoxic cell phenotype (TIA-1+, granzyme B-). Most patients were CD4-/CD8- (16 of 18); CD56+ (15 of 18), expressed the Vdelta1epitope (Vd1+/Vd2-/Vd3-) (9 of 12); and were negative for Epstein-Barr virus (EBV) (18 of 20). Isochromosome arm 7q was documented in 9 of 13 patients. Eight patients had previously undergone kidney transplantation or had a history of systemic lupus, Hodgkin disease, or malaria. Prognosis was poor; median survival time was 16 months, and all but 2 patients ultimately died despite consolidative or salvage high-dose therapy. In conclusion, HSgammadeltaTCL is a disease with distinctive clinical, histopathologic, and phenotypic characteristics. Bone marrow biopsy with combined phenotyping is sufficient for diagnosis, and splenectomy is therefore unwarranted. Current treatment modalities appear to be ineffective in most patients.
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PMID:Hepatosplenic gammadelta T-cell lymphoma is a rare clinicopathologic entity with poor outcome: report on a series of 21 patients. 1290 41

Epstein-Barr virus (EBV) was discovered 40 years ago from examining electron micrographs of cells cultured from Burkitt's lymphoma, a childhood tumour that is common in sub-Saharan Africa, where its unusual geographical distribution - which matches that of holoendemic malaria -indicated a viral aetiology. However, far from showing a restricted distribution, EBV - a gamma-herpesvirus - was found to be widespread in all human populations and to persist in the vast majority of individuals as a lifelong, asymptomatic infection of the B-lymphocyte pool. Despite such ubiquity, the link between EBV and 'endemic' Burkitt's lymphoma proved consistent and became the first of an unexpectedly wide range of associations discovered between this virus and tumours.
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PMID:Epstein-Barr virus: 40 years on. 1551 Jan 57

Malaria and Epstein-Barr virus (EBV), recognised cofactors for endemic Burkitt's lymphoma, are ubiquitous within the lymphoma belt of Africa, and, unless other cofactors are involved, the tumour should be much more common than it is. Malaria and EBV alone cannot account for the occasional shifting foci and space-time case clusters of endemic Burkitt's lymphoma. Arboviruses and plant tumour promoters are other possible local cofactors that could explain such characteristics. The geographical and age distributions of endemic Burkitt's lymphoma parallel those of potentially oncogenic, mosquito-borne arboviruses. Arboviruses seem to be associated with case clusters of endemic Burkitt's lymphoma, and symptoms compatible with arbovirus infection have been seen immediately before the onset of the tumour. RNA and DNA viruses, including EBV, are promoted by extracts of a commonly used plant, Euphorbia tirucalli, the distribution of which coincides with the boundaries of the lymphoma belt. Extracts of E tirucalli are tumour promoters and can induce the characteristic 8;14 translocation of endemic Burkitt's lymphoma in EBV-infected cell-lines. They also activate latent EBV in infected cells, enhance EBV-mediated cell transformation, and modulate EBV-specific immunity.
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PMID:Is endemic Burkitt's lymphoma an alliance between three infections and a tumour promoter? 1558 45

The circumsporozoite (CS) is the most abundant surface protein of the Plasmodium sporozoite, and is also present early in the liver stage of the infection. Following successful protective experiments in mice and monkeys, the synthetic 102-mer malaria vaccine polypeptide representing the C-terminal region of the CS of Plasmodium falciparum was tested in a clinical trial with healthy human volunteers. This vaccine induced strong CD8(+), CD4(+) T lymphocyte and antibody responses specific for the immunizing peptide. CD8(+) T lymphocyte responses elicited in HLA-A*0201 volunteers recognized two well-defined cytotoxic T lymphocyte epitopes within the CS. Here, we show that both monocyte-derived dendritic cells (Mo-DC) and Epstein-Barr virus-transformed B-lymphoblastoid cells (LCL) can present a cytotoxic T lymphocyte epitope contained within the 102-mer synthetic peptide. Paraformaldehyde and low temperature inhibited presentation, indicating that cellular processing was required. Using specific inhibitors, we show that, in both cell types, processing requires the proteasome and the MHC class I pathway, while the endosomal compartment appears to be critical only for the presentation by Mo-DC. Antigen uptake is associated with actin polymerization in both cell types. These in vitro results demonstrate the likely pathway of antigen presentation achieved via vaccination with this synthetic peptide.
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PMID:MHC class I-restricted exogenous presentation of a synthetic 102-mer malaria vaccine polypeptide. 1568 45

Perennial and intense malaria transmission (holoendemic malaria) and Epstein-Barr virus (EBV) infection are 2 cofactors in the pathogenesis of endemic Burkitt lymphoma (eBL). In the present study, we compared EBV loads in children living in 2 regions of Kenya with differing malaria transmission intensities: Kisumu District, where malaria transmission is holoendemic, and Nandi District, where malaria transmission is sporadic. For comparison, blood samples were also obtained from US adults, Kenyan adults, and patients with eBL. Extraction of DNA from blood and quantification by polymerase chain reaction give an EBV load estimate that reflects the number of EBV-infected B cells. We observed a significant linear trend in mean EBV load, with the lowest EBV load detected in US adults and increasing EBV loads detected in Kenyan adults, Nandi children, Kisumu children, and patients with eBL, respectively. In addition, EBV loads were significantly higher in Kisumu children 1-4 years of age than in Nandi children of the same age. Our results support the hypothesis that repeated malaria infections in very young children modulate the persistence of EBV and increase the risk for the development of eBL.
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PMID:Exposure to holoendemic malaria results in elevated Epstein-Barr virus loads in children. 1577 68


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