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)

Plasma membranes of normal duckling erythrocytes were prepared by blender homogenization and nitro-en decompression. Surface membrane vesicles of red cells infected with the avian malaria Plasmodium lophurae were produced by nitrogen decompression. Membranes of erythrocyte-free malaria parasites were removed from cytoplasmic constituents by Dounce homogenization. These membranes were collected by centrifugation in a sucrose step gradient and purified on a linear sucrose gradient. Red cell membranes had a buoyant density of 1.159 g/cm3, whereas plasmodial membranes banded at 2 densities: 1.110 g/cm3 and 1.158 g/cm3. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the isolated red cell membranes revealed 7 major protein bands with molecular weights (MW) ranging from 230, 000 to 22,000, and 3 glycoprotein bands with MW of 160,000, 88,000 and 37,000. Parasite membranes also had 7 major bands with MW ranging from 100,000 to 22,000. No glycoproteins were identifiable in these membranes. The proteins of the surface membranes from infected red cells had MW similar to those from normal red cells; however, there was some evidence of a reduction in the amount of the high MW polypeptides. The red cell membrane contained 79 nmoles sialic acid/mg membrane protein, whereas plasmodial membranes had 8 nmoles sialic acid/mg membrane protein. The sialic acid content of the surface membranes of infected red cells was significantly smaller than that of normal cells. Lactoperoxidase-glucose oxidase-catalyzed iodination of intact normal and malaria-infected erythrocytes labeled 7 surface components. Although no observable differences in iodinatable proteins were seen in these preparations, there was a striking reduction in the iodinatability of erythrocytic membranes obtained from P. lophurae-infected cells. Erythrocyte-free plasmodia bound very little radioactive iodine; the small amount of radioactivity was distributed among 3 major bands with MW of 42,000, 32,000 and 28,000. It is suggested that the alterations of the surface of the P. lophurae-infected erythrocyte do not occur by a wholesale insertion of plasmodial membrane proteins into the red cell plasma membrane, but rather that there are parasite-mediated modifications of existing membrane polypeptides.
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PMID:Plasmodium lophurae: membrane proteins of erythrocyte-free plasmodia and malaria-infected red cells. 53 38

A novel fixative and permeabilization method is described which allows simultaneous flow cytometric detection of red blood cell membrane antigen and intracellular malaria parasites. To illustrate the method, red blood cells from patients with paroxysmal nocturnal hemoglobinuria were infected with Plasmodium falciparum and maintained in synchronous red blood cell culture. The infected red blood cells were immunolabeled with antibodies directed to the complement regulatory protein decay-accelerating factor (DAF) followed by subsequent fixations in paraformaldehyde and then glutaraldehyde in phosphate-buffered saline. Finally, DNA of the intraerythrocytic parasites was stained with propidium iodide. Using this technique, cellular morphology was well preserved, no cell aggregation was observed, and high-quality indirect immunofluorescence and parasite DNA staining were obtained with negligible nonspecific labelling. Simultaneous measurement of parasite DNA and red blood cell membrane determinants makes possible the investigation of alterations of red cell membrane proteins in association with development of intracellular malaria parasites.
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PMID:Flow cytometric two-color staining technique for simultaneous determination of human erythrocyte membrane antigen and intracellular malarial DNA. 137 10

WHO finds that the health services and the health systems in India have improved. For example, India has made considerable improvement in expansion of health services to rural areas (7-10% expansion) and to the poor. Further, allocation to the minimum needs program, according to the state sector plan, has risen from 42.6% to 50%. In addition, infant and maternal mortality rates have fallen. Improved immunization coverage, prenatal care services, diarrhea prevention, malaria control, and contraceptive use have all contributed to the reduction in infant and maternal deaths. Health and welfare programs have generally institutionalized the primary health care concept of community participation. Training for health workers, policymakers, and personnel from nongovernmental organizations has expanded. Nevertheless, life expectancy has essentially not changed. Besides, WHO notes that the disease patterns have not changed. Some regions of India have disease patterns of developed countries, however. India has the highest number of malaria cases in southeastern Asia (almost 71%) and the second highest number of women with anemia. The number of HIV-positive and AIDS cases is growing. More than 374 million people are at risk of lymphatic filariasis, and Japanese encephalitis has become entrenched in India. 5% of the population are positive for hepatitis viruses. 1% have iodine deficiency disorders.
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PMID:WHO commends India. 145 31

With the osmium tetroxide-zinc iodide impregnation technique the visualization of the internal organization of the exoerythrocytic form of the rodent malaria parasite Plasmodium berghei was improved. Osmium impregnation leached the ground matrix of the parasite thereby displaying a system of intermediate-sized filaments. Because microtubules are only present as part of the mitotic spindle and as remnants of the sporozoite cytoskeleton, the observed intermediate-sized filaments comprise most of the cytoskeletal organization of the liver stage malaria parasite.
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PMID:Organization of the exoerythrocytic stage of the rodent malaria parasite Plasmodium berghei. A cytochemical study. 353 27

Previous studies of thyroid function during various infections have yielded conflicting results, but most have suggested an acceleration of peripheral thyroxine (T(4)) turnover during the acute infectious illness. In the present studies, thyroid function was examined by a method allowing simultaneous analysis of both endogenous thyroidal release and peripheral T(4) disposal in normal volunteers after induction of acute falciparum malaria. Subjects received iodide-(125)I, followed in 5-7 days by (131)I-T(4) intravenously. 4 days later, infection was induced by the injection of parasitized red blood cells. Bidaily measurements of serum protein-bound (125)I and protein-bound (131)I, and urinary (125)I and (131)I, together with frequent estimates of serum (127)I-T(4) (Murphy-Pattee) and free T(4) (FT(4)), were made during a control period, during acute illness, and during convalescence. Alterations in the peripheral metabolism of (131)I-T(4) during infection included significant decreases in the fractional disappearance rate for T(4) [(k)], and in the clearance and daily disposal of T(4), all of which returned to control values during convalescence. Total serum (127)I-T(4) increased late in the infected period to become greater during convalescence than either before or during infection, while FT(4) did not increase significantly until convalescence. An analysis of serum (131)I-T(4)/(127)I-T(4) and (131)I-T(4)/PB(125)I ratios confirmed these observations. The slope with time of ratios for urinary (125)I/(131)I, a reflection of thyroidal iodine release, was decreased during infection, but rebounded to control values during the convalescent period. The observed increments in serum (127)I-T(4) concentration in the convalescent phase may reflect in part the slowing of (k), but together with the rising ratios of urine (125)I/(131)I suggests enhanced thyroidal T(4) secretion immediately after the acute illness. Thus, with malarial infection, there appears to be an initial depression followed by a rebound in rates of thyroidal iodine release. In contradistinction to other infections, fractional turnover and daily disposal of hormone is decreased in malaria, perhaps due to hepatic dysfunction and the consequent impairment in cellular deiodinative processes.
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PMID:Alterations in thyroid iodine release and the peripheral metabolism of thyroxine during acute falciparum malaria in man. 456 63

The impact of acute malaria infection on the level of spontaneous apoptosis, i.e., the percentage of apoptotic cells detectable in lymphocytes cultured without any exogenous stimulus for 3 days in vitro, was evaluated. Quantitation of apoptosis was performed by staining of lymphocyte nuclei with propidium iodide and analysis of the fluorescence by cytometry. The mean apoptosis of 23 HIV-negative patients (15 Africans and 8 Europeans) determined during a confirmed Plasmodium falciparum attack was 27.2% (95% confidence interval (CI) = 23.5-30.7%) i.e., 2.2 times the mean level found in 49 controls (12.4%, CI = 11.1-13.6). These controls included age- and sex-matched Africans (n = 37) and Europeans (n = 12) differing only by their previous level of exposure to P. falciparum. Naive (European) as well as previously exposed (African) subjects showed dramatically elevated levels of spontaneous apoptosis during the malaria attack (mean = 22.5%, CI = 20.7-24.4 for Europeans; mean = 29.7%, CI = 24.6-34.7 for Africans). Such unusually raised levels were observed for at least 1.5 months and were probably detectable for longer periods as suggested by the fact that the mean level of spontaneous apoptosis in healthy Africans was basically higher (13.8%, CI = 12.5-15) than the one found in healthy Europeans (8.2%, CI = 6.3-10.1) (P = 0.0001). Selective immunomagnetic cell isolations carried out immediately before apoptosis quantitation showed that this process affected not only the alpha beta T cells (CD4+ T cells as well as CD8+ T cells) but also the gamma delta T cells and the B-lymphocyte subset.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute Plasmodium falciparum infection is associated with increased percentages of apoptotic cells. 759 Sep 29

Malaria diagnosis relies on observation of parasites in blood smears and the Giemsa-stained thick blood smear (G-TS) is the reference test. Diagnosis by G-TS in low-density infections requires long periods of observation and experienced microscopists. Examination of Giemsa-stained thin smears enables more reliable differentiation of species but may miss low-grade infections. Fluorescent stains may offer an alternative technique. We compared the Giemsa technique with 4,6-diamidine-2-phenilindolo-propidium iodide (DAPI-PI) stainings in order to evaluate the time required for diagnosis. A Plasmodium falciparum-infected blood specimen was diluted to obtain concentrations ranging from 6192 to 24 parasites/microliters (p/microliter), and thin and thick smears were stained with the two methods. The DAPI-PI proved useful: parasites were easily recognized and their morphology was preserved in thin and thick smears. The method allowed more rapid evaluation of thin smears as compared with Giemsa staining and enabled recognition of parasites in case of low-level parasitemias. The DAPI-PI staining technique may acquire an important role in malaria diagnosis, especially in nonendemic countries where technicians are not experienced with G-TS; in developing countries, it could be used in epidemiologic surveys of populations with low-density parasitemias, for which it enables a fast examination of smears and possibly the identification of parasite species.
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PMID:Rapid diagnosis of malaria by use of fluorescent probes. 811 44

A method for fixation of Plasmodium falciparum infected erythrocytes and solubilization of the erythrocyte membrane with detergent was developed. This method was applied to two-color flow cytometric analysis of both intraerythrocytic (IE) malaria DNA and parasite-derived antigen on the erythrocyte surface membrane. Infected erythrocytes were fixed with 0.025% glutaraldehyde followed by treatment with 1% saponin to gain access to intramembranous components and allow antibody to interact with antigen. DNA of IE parasite was subsequently stained with propidium iodide. Using this procedure cell morphology was well preserved with excellent parasite DNA staining. Using anti-malaria antibodies which recognize ring-infected erythrocyte surface antigen (Pf155/RESA), we observed that glutaraldehyde-fixed saponin treated infected erythrocytes exhibited a variable immunofluorescence intensity as assessed by both flow cytometry and fluorescence microscopy. Ring-infected cells displayed strong immunofluorescence staining, whereas a weak signal was detected on cells containing schizonts. Simultaneous measurement of parasite DNA and antigen in the infected erythrocyte membrane can facilitate the study of antigen expression in the cell membrane in association with development of IE parasites.
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PMID:Two-color flow cytometric analysis of intraerythrocytic malaria parasite DNA and surface membrane-associated antigen in erythrocytes infected with Plasmodium falciparum. 851 99

The resurgence of drug-resistant malaria makes urgent the evaluation of new antimalarial agents. This study describes a flow cytometric method (FCM) for testing in vitro drug susceptibility of Plasmodium falciparum malaria to several orally active hydroxypyridinone (CP) iron chelators and to the parenteral iron chelator desferrioxamine (DF). After exposure of parasites to various concentrations of iron chelating agents, aliquots of cultures were fixed with glutaraldehyde. The fixed samples were washed and stained for parasite DNA with propidium iodide and analyzed by flow cytometry. The remaining cells were pulsed with 3H-hypoxanthine, using the microdilution radioisotope method. Both CP and DF showed dose-dependent inhibition of parasite growth. Of the compounds studied, DF exerted a stronger inhibitory effect. Fifty percent of inhibitory concentrations (IC50) of CP and DF determined by DNA fluorescence profiles in the flow cytometer were consistent with those obtained from the radioisotope method and by microscopic examination. Moreover, the minimum inhibitory concentrations (MIC) of drug required to inhibit parasite growth, as detected by the decreasing DNA fluorescence intensity of the schizont, correlated with observed abnormal microscopic morphology. The validity of the MIC, as indicated by decreased fluorescence intensity, was confirmed by subsequent parasite culture. Our FCM study demonstrated the sensitivity of both chloroquine- and pyrimethamine-resistant malaria parasites to iron chelators. Addition of equimolar concentrations of ferric ion completely abolished the inhibitory effect of iron chelators, indicating the importance of iron for parasite growth and the primary effect of the compounds as iron (III) chelating agents. These data demonstrate that FCM provides a simple and reliable means for antimalarial drug susceptibility testing, and suggest that iron chelators have potential for the treatment of drug-resistant malaria.
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PMID:Flow cytometric assessment of hydroxypyridinone iron chelators on in vitro growth of drug-resistant malaria. 900 May 89

At present, approaches to studying mitochondrial functions in malarial parasites are quite limited because of the technical difficulties in isolating functional mitochondria in sufficient quantity and purity. We have developed a flow cytometric assay as an alternate means to study mitochondrial functions in intact erythrocytes infected with Plasmodium yoelii, a rodent malaria parasite. By using a very low concentration (2 nM) of a lipophilic cationic fluorescent probe, 3,3'dihexyloxacarbocyanine iodide, we were able to measure mitochondrial membrane potential(DeltaPsim) in live intact parasitized erythrocytes through flow cytometry. The accumulation of the probe into parasite mitochondria was dependent on the presence of a membrane potential since inclusion of carbonyl cyanide m-chlorophenylhydrazone, a protonophore, dissipated the membrane potential and abolished the probe accumulation. We tested the effect of standard mitochondrial inhibitors such as myxothiazole, antimycin, cyanide and rotenone. All of them except rotenone collapsed the DeltaPsim and inhibited respiration. The assay was validated by comparing the EC50 of these compounds for inhibiting DeltaPsim and respiration. This assay was used to investigate the effect of various antimalarial drugs such as chloroquine, tetracycline and a broad spectrum antiparasitic drug atovaquone. We observed that only atovaquone collapsed DeltaPsim and inhibited parasite respiration within minutes after drug treatment. Furthermore, atovaquone had no effect on mammalian DeltaPsim. This suggests that atovaquone, shown to inhibit mitochondrial electron transport, also depolarizes malarial mitochondria with consequent cellular damage and death.
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PMID:Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. 902 Jan


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