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 candidate Plasmodium falciparum sporozoite vaccine, R32tet32, which includes 32 tetrapeptide repeats derived from the circumsporozoite protein of P. falciparum, has been developed on the basis of the hypothesis that antibodies to the repeat region of this protein will protect against sporozoite infection. The results of two in vitro assays, the circumsporozoite precipitation reaction and the inhibition of sporozoite invasion into hepatoma cells, are thought to indicate protective immunity. We therefore tested serum samples from persons living in a hyperendemic malarious area of Indonesia for antibodies against R32tet32 and for their ability to produce circumsporozoite precipitation and to inhibit sporozoite invasion of hepatoma cells. The prevalence and mean titer of antibody against R32tet32 increased with the age of the subjects, whereas the prevalence of P. falciparum infection in the community decreased. Only serum samples with IgG or IgM R32tet32 antibody titers greater than or equal to 1/800 had precipitation activity and invasion-inhibiting activity of more than 75 percent. When the serum samples were fractionated by affinity chromatography, only the fractions containing purified human antibody to R32tet32 were found to contain this activity. These data support the hypotheses that antibodies to the circumsporozoite protein are important in reducing the prevalence of malaria with increasing age among persons in areas in which malaria is endemic and that vaccine-elicited antibody to the circumsporozoite repeat region will protect against infection with P. falciparum sporozoites.
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PMID:Immunity to malaria and naturally acquired antibodies to the circumsporozoite protein of Plasmodium falciparum. 352 48

Because of difficulties in cultivation of the exoerythrocytic (EE) stages of mammalian malaria parasites, investigation of the development of the EE stages has been hindered as compared to that of the other stages. Recently, human hepatoma cells (HepG2-A16) have been shown to be useful for the complete developmental cycle of the EE stage of Plasmodium berghei. In order to define the morphological events during this process, we evaluated the EE stages developing from sporozoites in these human hepatoma cells using electron microscopy and compared their structure to those grown in vivo. This study demonstrates that sporozoites of P. berghei can transform into EE stages within the hepatoma cells in a manner morphologically identical to that seen in vivo, and suggests that this cell line is a useful model for the study of the EE stages of mammalian malaria parasites.
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PMID:Ultrastructure of in vitro cultured exoerythrocytic stage of Plasmodium berghei in a hepatoma cell line. 609 67

The relationship between viruses and naturally occurring cancers, such as hepatocellular carcinoma and genital cancers, is of great importance to Africa. On the other hand, lymphomas, leukaemias and immunodeficiencies, although of less immediate public health importance, constitute an area of outstanding interest for research and their association with the Epstein-Barr virus (EBV) and the newly discovered human retroviruses merits world-wide attention. EBV-related malignancies in Africa include both Burkitt's lymphoma (BL) and nasopharyngeal carcinoma (NPC). Whether X-linked polyclonal lymphoproliferations exist in Africa remains an open question. The interrelationship between EBV, holoendemic malaria and genetic factors (oncogenes) has been deciphered in recent years, to make BL a kind of Rosetta stone for the understanding of multistage carcinogenesis. Although the role of EBV in the causation of NPC is not well understood, the viral capsid antigen (VCA) IgA test already allows both early detection of NPC in high-incidence areas and differential diagnosis in low-incidence areas. The question whether an EBV vaccine would be of value in African countries, in relation to EBV-associated malignancies, remains an open one. The diseases associated with the recently discovered human retroviruses (human T-lymphocyte leukaemia viruses: HTLVs) represent a new area for both research and public health assessment. Limited information is available today on the geographical distribution, age prevalence and association with disease in Africa of the different members of the retrovirus family (HTLV-1, HTLV-2, LAV/HTLV-3). The proportion of HTLV-related T-cell malignancies in different parts of Africa as well as the importance of immunodeficiencies caused by the different members of the retrovirus family remain to be determined. Typical acquired immunodeficiency syndrome (AIDS) appears to exist in Central Africa, especially Zaire, and HTLVs could be of public health importance if they cause severe forms of viral, bacterial or parasitic diseases through impairment of cell-mediated immunity. Africa, is and will long remain a continent of crucial importance with regard to the role of viruses in human malignancies and especially in haematopoietic proliferative disorders.
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PMID:Virus-associated lymphomas, leukaemias and immunodeficiencies in Africa. 610 Feb 86

Plasmodium falciparum and P. vivax sporozoites were observed to invade cultured human hepatoma cells in vitro. Monoclonal antibodies to the circumsporozoite (CS) protein of each of these malarial species blocked invasion. Inhibition was species-specific, but was independent of the geographic origin of each strain. Because these monoclonal antibodies have been shown to diminish or abolish sporozoite infectivity to susceptible primate hosts, it is suggested that inhibition of invasion of sporozoites (ISI) into cultured cells may represent in in vitro assay for protective antibodies. This was confirmed by the finding that serum taken from volunteers immune to sporozoite challenge also totally blocked sporozoite invasion. The ISI assay also detected naturally acquired invasive-neutralizing antibodies in areas endemic for malaria. This ISI assay may therefore be useful in determining the incidence of inhibitory anti-sporozoite antibodies in general populations, and allow the monitoring of the effect of an anti-malarial vaccine using sporozoite-derived antigens.
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PMID:Inhibition of entry of Plasmodium falciparum and P. vivax sporozoites into cultured cells; an in vitro assay of protective antibodies. 631 52

Ultrastructural localization of CD36 in human hepatic sinusoidal lining cells, hepatocytes, human hepatoma (HepG2-A16) cells, and C32 amelanotic melanoma cells. Experimental Parasitology 79, 383-390. CD36 is expressed in the endothelial cells of some human organs, but the ultrastructural localization of this molecule in the sinusoidal lining cells of human liver is not well established. We report the ultrastructural localization of CD36 in the liver using a novel murine monoclonal antibody against CD36, namely MO30, as a primary antibody. Immunocytochemistry by the postembedding method showed that CD36 was localized in endothelial cells of sinusoids and in hepatocyte microvilli protruding into the space of Disse. Moreover, in cultured human hepatoma (HepG2-A16) cells and C32 amelanotic melanoma cells, MO30 reacted with microvilli. Hence, CD36 expressed on these cells may be involved in recognition and/or entry of these cells by malaria sporozoites.
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PMID:Ultrastructural localization of CD36 in human hepatic sinusoidal lining cells, hepatocytes, human hepatoma (HepG2-A16) cells, and C32 amelanotic melanoma cells. 752 38

Volunteers immunized with gamma-irradiated Plasmodium falciparum sporozoites serve as the gold standard for protective immunity against mosquito-borne malaria transmission and provide a relevant model for studying protective immune effector mechanisms. During a 7-12 month period, we immunized four volunteers via the bites of irradiated, infected mosquitoes. Following these exposures to attenuated sporozoites, all four volunteers developed antibodies to sporozoites as measured by an immunofluorescence assay and by an enzyme-linked immunosorbent assay using the circumsporozoite (CS) protein repeat-based molecule R32LR as capture antigen. Three volunteers also developed antibodies against the nonrepeating (flanking) regions of the CS protein; the level of these antibodies paralleled the serum activity to inhibit sporozoite invasion of hepatoma cells in vitro. These three volunteers were protected against malaria transmitted by the bites of five infected mosquitoes. Two of these protected volunteers received additional immunizing doses of irradiated sporozoites and were subsequently protected against challenge with a heterologous P. falciparum clone. No detectable fluctuations were observed in circulating levels of tumor necrosis factor, interferon-gamma, or interleukin-6 during the course of this study. Analysis of the humoral and cellular immune responses of these protected volunteers is expected to yield important clues to additional targets of immunity against the pre-erythrocytic stages of malaria parasites.
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PMID:Humoral immune responses in volunteers immunized with irradiated Plasmodium falciparum sporozoites. 835 78

Exoerythrocytic stages of Plasmodium berghei cultured in HepG2-A16 hepatoma cells and those of P. falciparum in human hepatocytes transplanted under the kidney capsule of CB-17/ICr scid/scid mice were used to evaluate expression of heat-shock-related stress proteins. Although undetectable in the sporozoites, the expression of proteins similar in sequence of a heat-shock protein of 70 kDa and a glucose-regulated protein of 78 kDa was markedly induced in the hepatic stages of malaria parasites. Expression of these proteins in the exoerythrocytic stages of the malaria parasite warrants a systematic evaluation of their potential role in eliciting cellular immune responses directed against infected hepatocytes.
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PMID:Expression of members of the heat-shock protein 70 family in the exoerythrocytic stages of Plasmodium berghei and Plasmodium falciparum. 847 27

Plasmodium falciparum parasites develop in the liver before being released into the bloodstream, where they exert the potentially lethal effects characteristic of malaria. Our understanding of the hepatic phase of the life cycle is limited by the parasite's requirement for fresh human liver cells in which to mature. In this work, liver parasites completed their development within a Thai human hepatoma cell line (HHS-102), and the presence of ring-form parasites in erythrocytes overlying the liver cell culture confirmed that an entire liver cycle was completed, culminating in the production of viable blood-stage parasites. The HHS-102 cell line allows investigation of the undefined liver stage of falciparum malaria previously unavailable in the laboratory.
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PMID:Complete development of the liver stage of Plasmodium falciparum in a human hepatoma cell line. 856 Dec 62

We investigated the immunogenicity and the conformational properties of the non-repetitive sequences of the Plasmodium falciparum circumsporozoite (CS) protein. Two polypeptides of 104 and 102 amino acids long, covering, respectively, the N- and C-terminal regions of the CS protein, were synthesized using solid phase Fmoc chemistry. The crude polypeptides were purified by a combination of size exclusion chromatography and RP-HPLC. Sera of mice immunized with the free polypeptides emulsified in incomplete Freund's adjuvant strongly reacted with the synthetic polypeptides as well as with native CS protein as judged by ELISA and IFAT assays. Most importantly, these antisera inhibited the sporozoite invasion of hepatoma cells. In addition, sera derived from donors living in a malaria endemic area recognized the CS 104- and 102-mers. Conformational studies of the CS polypeptides were also performed by circular dichroism spectroscopy showing the presence of a weakly ordered structure that can be increased by addition of trifluoroethanol. The obtained results indicate that the synthetic CS polypeptides and the natural CS protein share some common antigenic determinants and probably have similar conformation. The approach used in this study might be useful for the development of a synthetic malaria vaccine.
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PMID:Synthesis and immunological characterization of 104-mer and 102-mer peptides corresponding to the N- and C-terminal regions of the Plasmodium falciparum CS protein. 864 99

1. The liver is ideally suited for the efficient uptake of drugs from sinusoidal blood. For most drugs, uptake into hepatocytes across the basolateral membrane occurs via passive diffusion, with minimal reliance on carrier-mediated transport systems. Often, this passive diffusion is so efficient that uptake is rate-limited by the delivery of the drug to the liver (i.e. blood flow) rather than membrane transport per se. 2. For highly polar molecules, passive diffusion no longer represents an efficient mode of hepatocellular uptake and there is an increased reliance on carrier-mediated transport systems. For these compounds, membrane transport may dictate the overall efficiency of hepatic elimination. 3. Drug metabolites, particularly conjugated metabolites, such as sulphates and glucuronides, are invariably more polar than their precursors and are more likely to experience hepatocyte membranes as diffusional barriers. In the presence of such a barrier, the hepatocellular disposal of a locally formed metabolite will depend critically on the presence and activity of carrier-mediated transport systems for sinusoidal efflux and biliary excretion. Transporters of current interest include P-glycoproteins, which are responsible for the biliary excretion of a range of organic cations, and the canalicular multispecific organic anion transporter. 4. Intracellular trapping of hepatically formed metabolites, secondary to low membrane permeability, is clinically important as many metabolites are potentially hepatotoxic and/or capable of interfering with the hepatic transport of endogenous compounds or other drugs and metabolites. In addition, if the metabolite is unstable, intracellular accumulation can lead to the regeneration of the precursor and 'futile cycling' within hepatocytes. 5. An increased understanding of the factors influencing the intracellular concentration of drugs and hepatically formed metabolites in the liver will improve our ability to specifically treat liver disorders, such as hepatocellular carcinoma and malaria, and minimize the risk of hepatotoxicity from drugs and other xenobiotics.
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PMID:Membrane transport as a determinant of the hepatic elimination of drugs and metabolites. 891 43


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