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Biomedical subjects

W Trager

Publications and source records attributed to W Trager.

At least 55 records · Page 3Linked to original sources
PubMed1980

Plasmodium falciparum in vitro: determination of chloroquine sensitivity of three new strains by a modified 48-hour test.

Three recently isolated African strains of Plasmodium falciparum were tested in vitro for their response to chloroquine. Both the 48-hour method described earlier and a modified 48-hour test were used, yielding comparable results. Strain FCR-7/Kenya, isolated from a clinically chloroquine-resistant case, was more resistant to the drug in vitro than the two other strains (FCR-8/West Africa and FCN-1/Nigeria, both isolated from chloroquine-sensitive cases). Complete inhibition of parasite growth occurred for strain FCR-7/Kenya in a drug concentration range ten times higher than for strains FCR-8/West Africa and FCN-1/Nigeria. In the modified 48-hour test, a lower erythrocyte suspension (2%) allows continuous growth of the parasites over a 48-hour cycle without necessitating change in medium. It thus offers distinct advantages for routine laboratory work as well as for potential field trials.

Chloroquine↗
PubMed1979

Tetraethylthiuram disulfide (Antabuse) inhibits the human malaria parasite Plasmodium falciparum.

Plasmodium falciparum in culture grows optimally at 3% oxygen. Oxygen levels down to 0.5% still support growth, but anaerobic conditions do not. These findings, and the absence of the Krebs cycle in Plasmodium, suggested that in this organism oxygen may not function in electron transport but rather may act through metalloprotein oxygenases. Tetraethylthiuram disulfide (Antabuse, disulfiram) and its reduction product diethyldithiocarbamate inhibit many metalloprotein oxygenases and have a lipid/H2O partition coefficient and high binding constant for metal ions, favoring selective toxicity to the malaria parasite. These compounds exhibited active antimalarial effects in vitro in concentrations down to 0.1 microgram/ml, the lowest level tested. Tetraethylthiuram disulfide at a level as low as 1 microgram/ml inhibited parasite glycolysis with no effect on glycolysis of normal erythrocytes. Erythrocytes pretreated with this drug at 10 microgram/ml did not support growth of the parasite.

Animals↗
PubMed1979

Plasmodium falciparum in culture: improved continuous flow method.

A new design of flow vessel provides a method for continuous culture of P. falciparum in a settled layer of human erythrocytes with a slow flow of culture medium over them. The parasitemia is kept fluctuating from approximately 1%, just after addition of fresh erythrocytes, to approximately 10%, 2 or 3 days later. Each vessel provides each week 3 harvests, each containing approximately 0.6--1 X 10(9) parasites.

Animals↗
PubMed1979

Isolation of stages of the human parasite Plasmodium falciparum from culture and from animal blood.

Procedures for isolation of various forms of the asexual erythrocytic stages of the human parasite Plasmodium falciparum are outlined. The procedures employ the plasma expander Physiogel, which is composed of a chemically modified, partially hydrolysed gelatin dissolved in Ringer's lactate. Based on the observation that parasitized cells which are easily separable by this technique differ appreciably at the ultrastructural level, a mechanism by which separation occurs is proposed.

Animals↗
PubMed1979

The role of hemoglobins C, S, and Nbalt in the inhibition of malaria parasite development in vitro.

The host cell competence of hemoglobin C (HbC)-containing erythrocytes for Plasmodium falciparum was studied by in vitro culture. HbC homozygous red cells did not support the growth of the intracellular parasite. Heterozygous cells, however, were competent. In addition, HbC increased the resistance of sicle cell hemoglobin (HbS) red cells when present in the double heterozygote, SC, cultured at low oxygen tension. This effect most likely resulted from the ability of HbC to enhance the sickling of HbS-containing red cells. Oxygenated SC cells were indistinguishable from normal and AS cells in host cell competence. Another double heterozygote, SNBalt, showed decreased sickling and decreased resistance to malaria parasite growth. The evolutionary significance of these results is discussed.

Animals↗
PubMed1979

Recent developments in enlarging the scale of production of Plasmodium falciparum in vitro.

Several methods are described for the cultivation of Plasmodium falciparum. They include cultivation in (a) flow vessels that contain 12 ml of RBC suspension and are harvested three times a week, (b) a "tipper" that provides a similar yield, and (c) more recently, a large flat-bottomed vessel that holds 75 ml of suspension. Attempts are being made to develop techniques for synchronizing the cultures.

Animals↗
PubMed1978

Sickling rates of human AS red cells infected in vitro with Plasmodium falciparum malaria.

The kinetics of sickling of malaria-infected red cells from humans with sickle cell trait were studied in vitro in an attempt to obtain direct experimental evidence for a selective advantage of the hemoglobin S heterozygote in a malarious region. The sickling rates of cells infected with Plasmodium falciparum and of non-infected cells were studied both in the total absence of oxygen (by dithionite addition) and at several different concentrations of oxyhemoglobin which might obtain in vivo. In all cases, red cells containing small plasmodium parasite forms (ring forms) sickled approximately eight times as readily as uninfected cells. Cells containing large parasitic forms (trophozoites and schizonts) appeared to sickle less readily than uninfected cells, by light microscopy criteria, but electron micrographs demonstrated the presence of polymerized deoxyhemoglobin S with a high frequency. It is concluded that enhanced sickling of plasmodium-infected AS cells may be one mechanism whereby the hemoglobin S polymorphism is balanced in favor of the heterozygote.

Anemia, Sickle Cell↗
PubMed1978

Chloroquine resistance produced in vitro in an African strain of human malaria.

After condinous cultivation in the presence of chloroquine, an African strain of the malaria parasite, Plasmodium falciparu, acquired resistance to the drug. The resistance was stable and comparable in vitro to that occurring naturally in a strain from Southeast Asia. This suggests that chloroquine resistance, absent until now in Africa, might arise in the future.

Animals↗
PubMed1978

Cultivation of malarial parasites.

The method for continuous cultivation of Plasmodium falciparum has now been successfully applied to several strains from different geographical areas. It has been used for tests of antimalarial drugs, for studies of parasite-host cell interactions with special reference to sickle haemoglobin, and for the production of amounts of parasite sufficient for experimental immunisation of Aotus trivirgatus monkeys.

ABO Blood-Group System↗