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)

Cytotoxic T lymphocytes (CTL) against the circumsporozoite (CS) protein of malaria sporozoites protect against malaria in rodents. Although there is interest in developing human vaccines that induce CTL against the Plasmodium falciparum CS protein, humans have never been shown to produce CTL against any Plasmodium species protein or other parasite protein. We report that when peripheral blood mononuclear cells (PBMC) from three of four volunteers immunized with irradiated P. falciparum sporozoites were stimulated in vitro with a recombinant vaccinia virus expressing the P. falciparum CS protein or a peptide including only amino acids 368-390 of the P. falciparum CS protein [CS-(368-390)], the PBMC lysed autologous Epstein-Barr virus-transformed B cells transfected with the P. falciparum CS protein gene or incubated with CS-(368-390) tricosapeptide. Activity was antigen specific, genetically restricted, and dependent on CD8+ T cells. In one volunteer, seven peptides reflecting amino acids 311-400 were tested, and, as in B10.BR mice, CTL activity was only associated with the CS-(368-390) peptide. Development of an assay for studying human CTL against the CS and other malaria proteins and a method for constructing target cells by direct gene transfection provide a foundation for studying the role of CTL in protection against malaria.
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PMID:Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein. 170 38

We report the isolation and sequencing of genomic DNA clones that encode the 1094-amino acid catalytic subunit of DNA polymerase delta from the human malaria parasite Plasmodium falciparum. Protein sequence comparison to other DNA polymerases revealed the presence of six highly conserved regions found in alpha-like DNA polymerases from different prokaryotic, viral, and eukaryotic sources. Five additional regions of amino acid sequence similarity that are only conserved in delta and delta-like DNA polymerases, so far, were present in P. falciparum DNA polymerase delta. P. falciparum DNA polymerase delta was highly similar to both Saccharomyces cerevisiae DNA polymerase delta (DNA polymerase III; CDC2) and Epstein-Barr virus DNA polymerase at the amino acid sequence, and the predicted protein secondary structure levels. The gene that encodes DNA polymerase delta resides as a single copy on chromosome 10, and is expressed as a 4.5-kb mRNA during the trophozoite and schizont stages when parasite chromosomal DNA synthesis is active.
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PMID:The primary structure of Plasmodium falciparum DNA polymerase delta is similar to drug sensitive delta-like viral DNA polymerases. 177 72

Chloroquine (CHL) has been suggested to play an important role in the development of Burkitt's lymphoma by enhancing Epstein-Barr virus expression. Herpes zoster virus incidence is markedly increased following malaria infection in children being treated with CHL. Recently, CHL has also been shown to dramatically increase the transactivation of Tat protein purified from human immunodeficiency virus. These previous studies indirectly suggest that CHL may be involved in the enhancement of virus replication. This study demonstrates for the first time that CHL indeed enhances Semliki Forest virus and encephalomyocarditis virus replication in mice. These results raise the possible connection between the increased spread of AIDS in endemic malaria areas and the wide use of CHL in those areas for the chemotherapy of malaria.
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PMID:Chloroquine enhances replication of Semliki Forest virus and encephalomyocarditis virus in mice. 184 12

Although the major diseases transmitted by transfusion today are AIDS and hepatitis, many others also are known. These include CMV, syphilis, Chagas disease, babesiosis, parvovirus B19, malaria, Epstein-Barr infection, and many others that have been reported only once or twice. Reducing the risk of transfusion-transmitted diseases is a problem for donor centers where donor screening and laboratory testing for possible carriers is undertaken. Physicians should be aware that the potential for disease transmission is always present when transfusions are administered.
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PMID:Transfusion-transmitted diseases other than AIDS and hepatitis. 196 3

Children living in hyperendemic malarious regions have high immunoglobulin levels and an increased frequency of Burkitt's lymphoma. In a study of Gambian children which endeavours to explain these findings we showed that acute P. falciparum malaria caused spontaneous activation and growth of their B lymphocytes in vitro. A high proportion of these cells contained Epstein-Barr nuclear antigen (EBNA). In ancillary experiments aimed at explaining these findings. CD4 helper cells from adult donors were destroyed with monoclonal antibody and complement. This manoeuvre resulted in loss of cytotoxic T cell control of their B lymphocytes when infected with Epstein-Barr virus (EBV). In children with acute malaria, both spontaneous immunoglobulin and antibody production by B cells was increased yet CD4 helper cell control over these cells, as measured by responses to pokeweed mitogen, was found to be intact. Spontaneous and concanavalin A-driven lymphocyte proliferation was depressed. We infer from these findings that in patients with P. falciparum malaria loss of cytotoxic T cell control of the EBV in B cells, possibly due to destruction or dysfunction of a subset of CD4 cells responsible for induction of suppressor/cytotoxic CD8 cells, leads to activation and proliferation of foci of B cells containing EBV. The expanded pool and rapid turnover of these cells may increase chances of malignant transformation leading to the genesis of Burkitt's tumor. Partial loss of suppressor mechanisms coupled with normal CD4 helper/inducer activity may result in high serum levels of immunoglobulin which are characteristic of persons living in malarious regions.
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PMID:The effects of Plasmodium falciparum malaria on immune control of B lymphocytes in Gambian children. 197 71

The B lymphocytes of the common marmoset Callithrix jacchus can be immortalized by infection with Epstein-Barr virus (EBV) in vitro (Desgranges et al., 1976). C. jacchus is susceptible to infection with the blood stages of several species of malaria parasite including the line designated MVF1 (Mitchell et al., 1988) from which it recovers and shows immunity to reinfection. By exploiting these two phenomena, EBV-transformed, marmoset lymphoblastoid cell lines secreting antibodies to malaria parasite antigens have been generated and cloned. We believe this to be the first time that monoclonal antibodies (MAbs) have been raised from common marmosets. Since numerous and diverse human pathogens can infect this small primate in the laboratory, these methods may prove generally applicable for the generation of MAbs whose specificities derive from immune responses to infection.
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PMID:Monoclonal antibodies from Epstein-Barr virus-transformed lymphocytes of common marmosets (Callithrix jacchus) immune to malaria. 215 67

Burkitt's lymphoma is the most common childhood cancer in Africa. Most prevalent in areas endemic for malaria, the disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumour of the jaw. When first characterized in the 1950s, the lymphoma was thought to spread by some infectious agent. Subsequent research indicates that the frequent involvement of an infectious agent is but one factor in a more complex aetiology. Today, Burkitt's lymphoma is considered an example of multistep carcinogenesis. Each step in the process results from a different agent. The agent in the first step is the Epstein-Barr virus, which infects B cells of the immune system causing a proliferation of these cells. The second step, malarial infection, furthers the proliferation of B cells providing a large population of cells available for a chromosomal translocation which represents the third step in the formation of the lymphoma. The chromosomal translocation places a cancer causing gene, c-myc, in close proximity to an active antibody-encoding its proliferation resulting in a cell capable of unlimited growth which serves as the nucleus of a B cell lymphoma.
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PMID:Burkitt's lymphoma and the role of Epstein-Barr virus. 216 60

Peripheral blood lymphocytes from healthy, Epstein-Barr virus (EB-virus)-seropositive donors and from patients with acute Plasmodium falciparum malaria were tested for their cytotoxicity towards autologous EB-virus-infected B-cells using an in vitro regression assay. Of the 18 cultures from control donors, 88.8% showed the normal pattern of regression. Of the 20 malaria patients in the study, 40% failed to exhibit the normal pattern observed in the control group. Analysis of the lymphocyte subsets showed a high incidence of inverted CD4:CD8 ratios in the patient group due to an absolute rise in the CD8 population. This data suggests that the immunosuppressive effects of acute malaria extend to defective control over EB-virus. The relevance of the observations to the aetiology of EB-virus-associated, endemic Burkitt's lymphoma (eBL) is discussed.
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PMID:In vitro analysis of Epstein-Barr virus: host balance in patients with acute Plasmodium falciparum malaria. I. Defective T-cell control. 216 84

Epstein-Barr virus and HTLV-1 are both lymphotropic viruses, capable of immortalizing lymphocytes in vitro (Fig. 1). Both viruses have been sequenced and subjected to intense molecular biologic scrutiny, and in both cases genes believed to be important in lymphocyte immortalization have been identified. These viral genes are not homologues of cellular oncogenes, nor is there any evidence to suggest insertional mutagenesis. Rather, these genes alter the expression of a variety of cellular genes and, in so doing, alter the growth characteristics of the host cell. Infection with either virus is most likely to be asymptomatic, associated with a benign self-limited lymphoproliferation, or both, but in a small fraction of instances these benign lymphoproliferations give rise to a lymphoma or leukemia. In the case of the Epstein-Barr virus, a variety of cofactors have been identified that are important to the evolution of malignancy. These cofactors include immunosuppression in transplant recipients, cogenital immunodeficiency in the X-linked lymphoproliferative syndrome, human immunodeficiency virus infection in AIDS patients, and malaria in patients with endemic Burkitt's lymphoma. In the case of HTLV-1, cofactors have not been identified. Nonetheless, the importance of cofactors is suggested by the small fraction of the population infected by the virus who actually develop lymphoproliferative disease, and the long latency period between infection and the development of frank lymphoproliferative disease. In organ transplant recipients with lymphomas associated with Epstein-Barr virus infection, the EBV immortalizing/transforming genes are expressed in the malignant tissue. But in Burkitt's lymphoma and in adult T-cell leukemia/lymphoma, the EBV and HTLV-1 immortalizing/transforming genes are not detectably expressed. In Burkitt's lymphoma, it is suggested that the dysregulated myc gene renders the growth effects of Epstein-Barr virus latency genes superfluous. No comparable proto-oncogene translocation or activation has yet been identified in HTLV-1 lymphoma/leukemia.
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PMID:Human lymphotropic viruses associated with lymphoid malignancy: Epstein-Barr and HTLV-1. 217 3

This review describes the transmission, clinical picture and immunological abnormalities of HIV infection in children in general, and the special problems of AIDS in African children. The review begins with a thorough introduction to the epidemiology of AIDS. Transmission to children generally involves vertical transmission by placental transfer or transmission of HIV via transfusion of blood and blood products, or by contaminated needles. Casual transfer is unknown, and only a few cases of transmission via breast milk are known. The clinical picture of HIV infection in infants and children differs from that in adults in 3 important aspects: earlier onset, different clinical presentation and existence of AIDS embryopathy. The average onset was 5 months of age. The most common symptoms in young children are chronic interstitial pneumonitis without demonstrable etiology, hepatomegaly, failure to thrive, adenopathy, diarrhea, oral or perineal thrush, eczema and thrombocytopenia. The common opportunistic infections are pneumocystis carinii pneumonia, cytomegalovirus, Epstein-Barr virus, Cryptosporidium diarrhea, pyogenic infections of the middle ear and gram-negative septicemia. Several infections seen in adult AIDS cases are rare in children: mycobacterium avium-intracellulare, toxoplasma gondii, hepatitis B, as well as Kaposi's sarcoma, malignant lymphoma and cardiac abnormalities. The AIDS embryopathy or HIV dysmorphic syndrome is characterized by immunological abnormalities, growth failure, and craniofacial dysmorphism, particularly microcephaly, prominent box-like forehead, hypertelorism, flattened nasal bridge, obliquity of the eyes, blue sclerae and patulous lips. AIDS in African children is extremely difficult to diagnose because of similarities between the presenting symptoms and those commonly seen in sick children there, many of whom are also immune compromised. Where serotesting is available, the picture is complicated by cross reaction between the test agents and some factor found in sera from malaria patients. Seropositivity in some areas is high, increased by the prevalence of transfusion and injection treatments. Diagnosis is made more difficult by lack of laboratory facilities and difficulties in follow-up for pediatric patients. The CDC definitions of AIDS and ARC, and the WHO/CDC definitions of AIDS are appended.
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PMID:Human immunodeficiency virus infection in childhood. 245 15


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