Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trypanosoma cruzi is the causative agent of Chagas' disease in man, often leading to suppression of T lymphocyte functions; the present study thus considered the effects of infection by T. cruzi on T-dependent immune responses in a murine model, namely, the immune resistance to a syngeneic tumour and a delayed-type hypersensitivity reaction to sheep red blood cells (SRBC). In BALB.B mice infected with T. cruzi, the graft of syngeneic Gross murine leukaemia virus-induced tumour cells leads to an increased incidence of progressive subcutaneous tumours and development of lymphatic leukaemia. This decreased resistance to tumours correlates with a suppression of the generation of tumour-specific cytolytic T lymphocytes (CTL) from the pre-CTL stage. In contrast, clonal expansion and circulation of T cells detected through their ability to locally transfer a delayed-type hypersensitivity (DTH) reaction to SRBC remained normal in T. cruzi-infected mice. However, at the site of the DTH reaction, a decreased availability of phagocytes was observed in T. cruzi-infected mice.
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PMID:Selective suppression of tumour-immune cytolytic T lymphocytes in mice with chronic Trypanosoma cruzi infections. 294 71

Serum samples from 850 individuals from Venezuela were tested for the presence of antibodies to HTLV-III/LAV virus, the probable etiological agent of acquired immune deficiency syndrome (AIDS). At the time of the study, none of the individuals tested had symptoms indicative of AIDS or related disorders. Viral antibodies were assayed by indirect immunofluorescence (IF) assay, using a chronically infected, HTLV-III/LAV producer cell line CEM/LAV-NIT established in our laboratory. Twenty individuals (2.5%), 8 of them (40%) female, were seropositive by IF and by confirmatory Western blotting and radioimmunoprecipitation assays. The seropositivity rate ranged from 2.4% (11 of 465) in the general healthy population, 4% (2 of 50) among patients with Chagas' disease, and up to 29.2% (7 of 24) among patients with acute malaria infection. The titers of HTLV-III/LAV antibodies ranged from 1:40 to 1:640. In addition, 2 of 36 patients with hemophilia A (5.5%) also had antibodies to HTLV-III/LAV. Two of 7 patients with acute malaria had specific antibodies both to HTLV-III/LAV and HTLV-I, as determined by IF and Western blotting. None of over 169 randomly chosen, healthy blood donors from seven major Venezuelan cities, as well as none of 99 patients with leukemia/lymphoma, had antibodies to HTLV-III/LAV. The presence of specific antibodies among various Venezuelan populations indicates that HTLV-III/LAV, or a closely related cross-reactive virus, is indigenous in Latin American subjects as was previously indicated for tropical populations of central Africa. Isolation and characterization of this virus will help to understand the origin and etiology of AIDS.
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PMID:Antibodies to acquired immune deficiency syndrome (AIDS)-associated virus (HTLV-III/LAV) in Venezuelan populations. 301 23

Given the dissemination of acquired immunodeficiency syndrome (AIDS) in Latin America, where Chagas' disease is endemic, there is a present and increasing risk of concurrent infections with human immunodeficiency virus (HIV) and Trypanosoma cruzi. We used the model of murine acquired immunodeficiency syndrome (MAIDS) caused by a murine leukemia virus (MuLV) that induces immunologic alterations with similarities to those accompanying human HIV infection to study aspects of concomitant infections. The MuLV infection was found to reactivate T. cruzi infection in C57Bl/10 mice, as indicated by elevated parasitemia and lymphocytic infiltration in the myocardium. The T cells from these animals did not respond to T. cruzi antigens (lymphocyte proliferation, interferon-gamma, or interleukin-2 [IL-2] production) but had increased levels of IL-10. Trypanosoma cruzi-specific antibody was decreased but not absent in dually infected animals. In a second set of experiments, we infected MAIDS-resistant B6D2 mice with MuLV, followed by infection with T. cruzi. These animals had higher parasitemia than those infected with T. cruzi alone. More interestingly, only dually infected animals developed MAIDS. The present report describes the activation of T. cruzi infection by MuLV as well as the aggravation of MuLV infection by T. cruzi. These results may be relevant to coinfections with retrovirus and protozoan parasites in humans.
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PMID:Aggravation of both Trypanosoma cruzi and murine leukemia virus by concomitant infections. 825 98

Violacein, a pigment produced by Chromobacterium violaceum, is reported to be a potential drug for the treatment of Chagas' disease. Violacein is also effective against leukemia and lymphoma cells in culture (IC50 10(-8) M). Changes in the nuclear acid content, 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide reduction and neutral red uptake in these cells were used to evaluate the cytotoxicity of violacein in V79 Chinese hamster (M-8) fibroblasts. Violacein was highly cytotoxic to V79 fibroblasts (IC50 5-12 microM). Using the TUNEL method and the Feulgen reaction coupled to image analysis, violacein (5 and 10 microM) was found to trigger apoptosis but not necrosis in V79 cells. The morphological changes seen in the nuclei of these cells included chromatin condensation and a decrease in deoxyribonucleic acid content. These results demonstrating that violacein induces apoptosis in V79 cells strengthen its potential as a therapeutic agent.
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PMID:Violacein cytotoxicity and induction of apoptosis in V79 cells. 1114 54

Chagas' disease is an endemic zoonosis of South America caused by a protozoan parasite Trypanosoma cruzi. About 30% of infected people develop the disease. This disease is known to reactivate in immunocompromised hosts, such as patients with acquired immunodeficiency syndrome, leukemia, and transplantation. There is some experience with transplantation of infected renal grafts into negative recipients, resulting in an index of transmission of 35%. No cases have been reported involving other organ transplants up to 2002, when the Centers for Disease Control and Prevention reported 3 cases of Chagas' disease transmission to 3 recipients (liver, kidney, and pancreas-kidney) from a single chagas infected donor. Here we report on a case of orthotopic liver transplant from a chagas infected donor into a negative recipient in clinical emergency status. The recipient was monitored by direct parasitological Strout method and serological tests with detection of transmission on the 84 th day by both studies, without clinical signs. The patient was put on benznidazole with rapid clearance of the parasitemia. However, we propose that chagas infected donors may be accepted for liver transplant recipients only in emergency status.
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PMID:Transmission of T. cruzi infection via liver transplantation to a nonreactive recipient for Chagas' disease. 1612 68

In the search for new metal-based drugs for the treatment of tumoral and parasitic diseases a vanadyl complex, [V(IV)O(SO(4))(H2O)(2)(dppz)].2H(2)O, that includes the bidentate polypyridyl DNA intercalator dipyrido[3,2-a:2',3'-c]phenazine (dppz), was synthesized, characterized by a combination of techniques, and in vitro evaluated on the human acute promyelocytic leukemia cell line HL-60 and against Dm28c strain epimastigotes of the parasite Trypanosoma cruzi, causative agent of Chagas' disease. EPR spectroscopy suggests a distorted octahedral geometry for the complex with the dppz ligand acting as bidentate, binding through both nitrogen donor atoms in an axial-equatorial mode. An oxo group, two water molecules and a sulphate donor occupy the remainder coordination positions. The complex, as well as the anti-trypanosomal reference drug Nifurtimox, showed IC(50) values in the muM range against T. cruzi Dm28c strain. In addition the complex exhibited excellent in vitro anti-tumor activity against leukemia (HL-60 cell line) comparable to that of cisplatin, inducing cell death by apoptosis with IC(50) values in the micromolar range. Data from gel electrophoresis and atomic force microscopy indicate that the complex interacts with DNA, suggesting that its mechanism of action may include DNA as a target. EPR and (51)V NMR experiments were also carried out with aged aerated solutions of the complex to get insight into the stability of the complex in solution and the species responsible for the in vitro activities observed.
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PMID:A novel vanadyl complex with a polypyridyl DNA intercalator as ligand: a potential anti-protozoa and anti-tumor agent. 1969 8

Tropical trees of Calophyllum genus (Calophyllaceae) have chemical and biological importance as potential source of secondary active metabolites which can lead to the development of new drugs. Research on this species has been rising since 1992 due to the discovering of anti-HIV properties of Calanolide A found in Calophyllum inophyllum leaves. This compound is the most important natural product for potential development of new anti-HIV drugs and phytomedicines. The scientometric analysis (1953-2014) here performed revealed that the most studied species of Calophyllum genus are: C. inophyllum and C. brasiliense, distributed in the Asian, and American continents, respectively. Current research on these species is carried out mainly in India and Brazil, respectively, where these species grow. Research on C. brasiliense is focused mainly on ecological, antiparasitic, cytotoxic properties, and isolation of new compounds. Chemical studies and biodiesel development are the main topics in the case of C. inophyllum. Text mining analysis revealed that coumarins, and xanthones are the main secondary active metabolites responsible for most of the reported pharmacological properties, and are potential compounds for the treatment of leukemia and against intracellular parasites causing American Trypanosomiasis and Leshmaniasis. On the other hand, C. inophyllum represents an important source for the development of 2nd generation biodiesel. Medicinal and industrial applications of these species may impulse sustainable forest plantations. To our knowledge this is the first scientometric and text mining analysis of chemical and biomedical research on Calophyllum genus, C. brasiliense and C. inophyllum.
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PMID:Trends in the chemical and pharmacological research on the tropical trees Calophyllum brasiliense and Calophyllum inophyllum, a global context. 3221 49