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)

In this report, the blood samples from 30 falciparum malaria patients with parasitemia 0.015-0.58% and the blood samples from 30 healthy persons were examined by monoclonal antibody (McAb) sandwich dot-immunogold silver staining assay (Dot-IGSSA). When the McAb 11G5, 13A2 and 13A1 were used for sandwich Dot-IGSSA with McAb 14D9 labeled with colloidal gold respectively, the 0.0001% of parasitemia could be detected and the McAb 11G5, 13A1 and 14D9 labeled with colloidal gold could also be used to detect the antigens of asexual blood stages of Yunnan and Anhui isolates of Plasmodium falciparum cultured in vitro. These McAbs did not cross-react with the antigens of Plasmodium knowlesi and Plasmodium berghei, however, the McAbs 13A1 and 14D9 weakly cross-reacted with the antigens of Plasmodium cynomolgi and the antigens in the infected blood samples from patients with vivax malaria.
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PMID:[Preliminary studies on the diagnosis of Plasmodium falciparum malaria by monoclonal antibody sandwich dot-immunogold silver staining assay]. 195 67

1. Monoclonal antibodies (MAbs) against surface antigens of Plasmodium gallinaceum sporozoites, an avian malaria parasite, were produced using spleen cells from mice immunized with sporozoites from mosquito salivary glands (SGS) or from midguts containing oocysts (OoS). 2. All of the 15 MAbs tested (11 anti-SGS and 4 anti-OoS) reacted with SGS and OoS by indirect immunofluorescence and circumsporozoite precipitation reactions. Fourteen of these MAbs (11 anti-SGS and 3 anti-OoS) produced a Western blot (WB) pattern identical to that produced with serum from mice hyperimmunized with viable intact sporozoites. 3. All MAbs and the immune sera recognized only two polypeptide bands of approximate molecular weight 76 and 64 kDa. 4. No difference in the WB pattern was observed when 9- or 12-day SGS or OoS extracts were used as antigens in WB. This antigenic similarity was confirmed when the total protein extracts were visualized on silver-stained SDS-PAGE gel.
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PMID:The immunodominant surface antigen of Plasmodium gallinaceum is present in both the salivary gland and oocyst sporozoites. 213 18

A specific enzyme-linked immunosorbent assay (ELISA) was developed for the detection and characterisation of antibodies directed against amodiaquine (AQ), an anti-malarial drug associated with agranulocytosis and liver damage in man. The assay incorporated an antigen which was produced by the reaction of amodiaquine quinone imine (AQQI), a protein reactive product produced from AQ by silver oxide oxidation, and metallothionein. The protein-conjugate (AQ-MT) had a ratio of AQ to protein of 5.2:1. Specific anti-drug antibody was defined as the differential binding to AQ-MT and unconjugated MT which was inhibitable by AQ-mercapturate (5 microM). Following administration of AQ (0.27 mmol/kg; for 4 days) to male Wistar rats there was a significant increase in the IgG anti-AQ activity on day 18 (P less than 0.05, 0.596 +/- 0.410, N = 7) compared to pre-injection levels (0.111 +/- 0.074, N = 7). This activity was shown to be specific for the AQ determinant by hapten inhibition with AQ (IC50 250 nM) and AQ-mercapturate (IC50 310 nM). Following administration of AQQI (27 mumol/kg; i.m.; 4 days) there was a significant increase in IgG anti-AQ antibody activities on day 18 (0.584 +/- 0.161, N = 7) compared to pre-injection levels (0.078 +/- 0.048, N = 7). This activity was inhibited by AQ (IC50 150 nM) and AQ-mercapturate (IC50 180 nM). In addition IgG anti-AQ antibodies were detected in four patients who exhibited agranulocytosis and one patient who exhibited hepatitis (range 0.017-0.842) whilst receiving AQ at a dose of 400 mg weekly for several weeks, but not in individuals who had not received the drug (-0.014 +/- 0.022, N = 7). There was no increase in IgG anti-AQ antibody activities in patients who had not exhibited an adverse reaction whilst receiving the drug for the treatment of malaria (-0.059 +/- 0.074 on day 0 and -0.053 +/- 0.068 on day 7, N = 13). Thus, we have shown that AQ is immunogenic in the rat and that the formation of a chemically reactive metabolite (AQQI) is involved in the generation of the antibody response. Furthermore, drug-specific antibodies were detected in sera from five patients with severe adverse reactions to the drug.
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PMID:Drug-protein conjugates--XVIII. Detection of antibodies towards the antimalarial amodiaquine and its quinone imine metabolite in man and the rat. 247 Mar 78

This paper presents results from analysis of a sample of SK&F 105154 (R32NS1(81], a malaria vaccine candidate produced in Escherichia coli, and discusses some analytical issues of general relevance to the characterization of such products derived from recombinant DNA technology. Anomalous migration and staining behavior were observed in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Reversed-phase liquid chromatography (RPLC) appeared to resolve four minor components from the principal band, but the minor peaks were found to consist of numerous components resolvable by SDS-PAGE. Western blotting visualized certain components that were not adequately stained by either Coomassie or silver stain. None of the techniques that were employed were individually adequate to characterize the sample, but, taken together, were adequate to characterize the sample and to identify one principal degradation pathway. Degradation within the NS1(81) region decreases the RPLC retention time, while degradation within the R32 segment increases the retention time.
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PMID:Reversed-phase liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis characteristics of a recombinant DNA derived malaria antigen. 306 Apr 76

Amounts of radio-labelled substances as low as 10(-18) moles incorporated into individual cells can be measured by utilizing techniques of quantitative autoradiography. For this purpose, radioactive standard sources are processed with the labelled cells smeared to slides. Carbon-14 is a favourable isotope with regard to minimal loss of beta-disintegrations due to self-absorption, and to limited cross-fire effects complicating the attribution of silver grains to individual cells. Silver grain densities can be counted by automated microphotometry allowing on-line data processing by an interfaced computer. Rate measurements of 14C-thymidine incorporation into individual cells yield values of the DNA synthesis rate provided that the endogenous pathway of thymidine-phosphate formation has been previously blocked. From the rate values of individual cells the DNA synthesis time of a cell compartment is derived. This is an essential time parameter for the evaluation of kinetic events in proliferating cell populations. This method is applicable to human cells without radiation hazard to man, and provides an optimal source of detailed information on the kinetics of normal and diseased human haematopoiesis. Examples of application consist of thalassaemia, malaria infection, iron deficiency anaemia and acute myelogenous leukaemia.
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PMID:Quantitative carbon-14 autoradiography at the cellular level: principles and application for cell kinetic studies. 701 61

The rates of switching between expression of variable antigen types (VATS) have been investigated in vivo in a cloned line of Plasmodium chabaudi chabaudi. VAT-specific hyperimmune sera combined with an immunogold-silver staining technique were used to detect VATS, and five estimates of VAT-specific switching rates were determined for three of them. VAT-specific switching rates were consistent for each VAT and differed between VATS in the range 1.3 x 10(-2) to 4.3 x 10(-4) switches per schizont per generation. This variation suggests that hierarchical expression of VATS in an infection may be determined by switch rates. A minimum estimate of the overall switching rate was determined by summation of the VAT-specific rates in each of two experiments. In both cases the results showed that at least 1 in every 80 schizonts switched VAT expression every generation. This is the first report of antigenic switching rates for malaria parasites measured in vivo in the presence of minimal specific immune pressure, and is the first to show that VAT-specific switching rates vary between VATS. We conclude that switching is rapid and spontaneous, and is regulated, at least in part, by the VATS involved.
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PMID:Malaria parasites undergo antigenic variation at high rates in vivo. 800 60

Sections of 18 malaria-infected placentas were stained with haematoxylin and eosin, periodic acid and methenamine silver, and immunohistochemically with monoclonal antibodies against human common leukocyte antigen, CLA (CD 45), B cells (CD 20, L 26), T cells (CD 45RO, UCHL-1) and collagen IV. Parasitized erythrocytes accumulated in the maternal villous spaces, with none in the foetal circulation. These were found in association with inflammatory leukocytes and pigments. Fibrinoid necrosis was more prevalent in the heavily infected placentas. Thickening and reduplication of foetal capillary basement membranes, and a decrease in leukocytes, including B and T cells, were seen in the heavily infected placentas. These findings are in keeping with previously reported depression of cellular and humoral immunity in patients with heavy parasitaemia.
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PMID:A histological and immunohistological study of malarial placentas. 853 33

Trephination and craniotomy performed by abrasion, scraping, crosscut sawing, and drilling are the oldest known surgical techniques used by primitive peoples. As a result of archaeological findings, the human skull is the most frequently studied part of the excavated body, leading to the creation of a new aspect of anthropology known as "cultural osteology." Found in ancient tombs, the human remains, mummies, skeletons, and their belongings, including war instruments, pottery, clothing, jewels, and surgical instruments, constitute the richest source of insight into the lives and pragmatic activities of ancient cultures. This study summarizes thousands of years of pre-Columbian history and medical evolution, specifically in the early and primitive practice of trephination, as precursors of neurosurgery. Comparative osteology studies have demonstrated that using primitive stone or metal instruments, the sirkaks (Inca surgeons) achieved an average survival rate of 50 to 70% of their craniectomy patients, with little incidence of infection or other complications. Despite their rudimentary knowledge of disease and pathology, a considerable knowledge of anatomy and natural medicine provided them with hemostatic agents, antiseptics, and other medical drugs, such as quinine for fever and malaria, as well as gold, silver, and other products to perform cranioplasties. Living in a world of continuous hand-to-hand combat, they also developed aggressive and defensive weapons that necessitated refinement of surgical techniques to save soldiers from battle wounds to their poorly protected crania.
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PMID:Preconquest Peruvian neurosurgeons: a study of Inca and pre-Columbian trephination and the art of medicine in ancient Peru. 1150 30

Retinol (vitamin A alcohol) may have a beneficial role in the host response to malaria in humans and previously published data have suggested that it has a direct inhibitory effect on the growth of Plasmodium falciparum in vitro. To further investigate the role of retinoids as potential antimalarial agents, we assessed the effect of all-trans-retinoic acid (RA), 9-cis-RA and 13-cis-RA, as well as retinol itself and its ester, retinyl palmitate, on 3H-hypoxanthine uptake by the laboratory-adapted strains of P. falciparum 3D7 and K1. In addition, we examined the influence of three specific RA receptor antagonists, ER 27191, Ro 415253 and AGN 194301, on retinoid-induced growth inhibition of 3D7. All-trans-RA, 9-cis-RA and 13-cis-RA in concentrations ranging from 1 x 10(-4) to 5 x 10(-10) M each had antimalarial activity, but at IC50 values (5.9 x 10(-5) to 7.9 x 10(-5) M) that were less than those of retinol (2.5 x 10(-5) to 3.2 x 10(-5) M). Retinyl palmitate had minimal effect on 3H-hypoxanthine uptake. Each of the three specific antagonists inhibited growth of 3D7 (IC50 range 1.2 x 10(-5) to 3.0 x 10(-5) M) but, in isobolographic analysis, were antagonistic to retinol (dose factor potentiation, DFP 0.46-0.79) and, in the case of Ro 415253, to all-trans-RA (DFP=0.39). Although we did not attempt to quantify losses of retinoids from the system, these data suggest that retinol has greater antimalarial activity than its RA metabolites and especially retinyl palmitate. The specific RA receptor antagonists showed paradoxical antimalarial activity but consistently antagonised the effect of retinol and all-trans-RA in isobolographic experiments. We conclude that RA metabolites may be less suitable than retinol per se as antimalarial agents and that P. falciparum might possess or acquire a RA receptor-like moiety.
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PMID:In vitro antimalarial activity of retinoids and the influence of selective retinoic acid receptor antagonists. 1287 28

Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (T(max)) produced by intact control and malaria-infected muscles before, during and after fatigue. Triton-skinned muscle fibres were isolated from these muscles and used to determine isometric contractile features as well as a basic biochemical profile as analysed by silver-enhanced SDS-PAGE. We found that the T(max) of intact muscles and the maximal Ca2+-activated force (F(max)) of Triton-skinned muscle fibres were reduced by approximately 50% in malarial muscles. In addition, the contractile proteins of Triton-skinned muscle fibres from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss of essential contractile proteins (e.g. troponins and myosin) in Triton-skinned muscle fibres from malarial muscles as compared to controls. The biochemical alterations (i.e., reduction of essential contractile proteins) seem to explain well the functional modifications resolved in both intact muscles and Triton-skinned muscle fibres and may provide a suitable paradigm for the aetiology of muscle symptoms associated with malaria.
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PMID:Functional and biochemical modifications in skeletal muscles from malarial mice. 1572 39


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