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J E Mrema

Publications and source records attributed to J E Mrema.

12 recordsLinked to original sources
PubMed1990

2-Chloroacetaldehyde and 2-chloroacetal are potent inhibitors of DNA synthesis in animal cells.

The effect of 2-chloroacetaldehyde, CAA, a metabolite of vinyl chloride and 2-chloroacetal, CAC, an ethyl diester of chloroacetaldehyde, on DNA synthesis in animal cells has been investigated. Both compounds drastically inhibited DNA synthesis at 10 to 20 microM. The inhibitory effect of the chemicals appears to be directly on DNA synthesis rather than on the uptake of thymidine or the formation of nucleotides. Residual DNA made in the presence of CAA had an average chain length of 300 nucleotides compared to a length of several thousand nucleotides in the absence of CAA. Synchronization experiments revealed that the inhibitory effect is reversible if 2-chloroacetaldehyde is removed within two hours but not after longer exposures.

Acetaldehyde↗
PubMed1987

Reference values for peripheral blood lymphocytes from Aotus lemurinus ssp. griseimembra (owl monkey).

The reactivities of several monoclonal antibodies that define human lymphocyte cell-surface antigens have been tested with peripheral blood lymphocytes of Aotus lemurinus ssp. griseimembra. Based on reactivity patterns in humans, reactive MoAb were identified that mark pan-T, helper/inducer, suppressor/cytotoxic, pan-B, and natural killer cells. Reference values of these subsets in Aotus are presented. These MoAb should provide a useful tool for further phenotypic and functional dissection of the immune system in this simian model of human disease.

Animals↗
PubMed1987

Erythrocytes and erythrocyte morphologies of healthy and colony-born owl monkeys (Aotus lemurinus griseimembra).

Inadequate availability of hematological reference data seriously restricts optimal utilization of the owl monkey (Aotus lemurinus griseimembra) as an experimental model. The current study investigated erythrocytic morphology in peripheral blood of healthy, colony-born owl monkeys. The blood of the subjects contained discoid erythrocytes, poikilocytes, and showed considerable anisocytosis. Also observed were nucleated erythrocytes, erythrocytes with Howell-Jolly bodies, and reticulocyte types I, II, and III. Heinz bodies were not detected.

Animals↗
PubMed1983

Identification of surface and internal antigens from spontaneously released Plasmodium falciparum merozoites by radio-iodination and metabolic labelling.

Spontaneously released merozoites from synchronous Plasmodium falciparum cultures were isolated in the presence of protease blocker. 1-5 X 10(10) merozoites were obtained in each experiment. The isolated merozoites possessed a thick surface coat and about 80% were invasive to human erythrocytes although they did not subsequently develop into ring stages. Tests using several analytical methods showed the merozoite preparations to be free of any erythrocyte contamination. Six labelled proteins were identified after surface radio-iodination, the largest with a molecular weight of 82 000. All six proteins were precipitated with various immune sera. Four other proteins with molecular weights of 200 000 and 160 000-145 000 (a triplet) were identified by precipitation with the same immune sera after metabolically labelling the merozoites. The six surface proteins were not prominent in the metabolically labelled preparations. Using these methods it is possible to identify and differentiate between surface and internal merozoite antigens.

Animals↗
PubMed1983

A rabbit--in vitro system to evaluate drug action against Plasmodium falciparum.

A rabbit-in vitro model system is described which can determine the activity of anti-malarial drugs against erythrocytic stages of Plasmodium falciparum. Serum samples, collected from rabbits at various times after drug administration, wee incubated with synchronized ring form parasites using the microtest system. The extent to which the presence of drugs in the serum inhibited parasite growth was usually determined after 32 to 40 hours of incubation. Anti-malarial activity was observed in sera obtained from rabbits which received chloroquine, mefloquine, pyrimethamine and cycloguanil, but not in those which received 4-4' diacetyldiaminodiphenylsulphone (DADDS). The effects against the drug-sensitive strain were more marked than against the drug-resistant one. The serum activity persisted for a longer period of time after administration of mefloquine, pyrimethamine, pamoate, and cycloguanil pamoate than after administration of chloroquine, a drug with a shorter biological half-life. The results indicate that this model may be a useful system for identifying potential agents against drug-resistant falciparum malaria, particularly compounds which are converted in vitro to their active metabolites or which exert a prolonged suppressive activity after drug administration.

Acedapsone↗
PubMed1983

Spirogermanium: a new drug with antimalarial activity against chloroquine-resistant Plasmodium falciparum.

Spirogermanium, a new investigational drug of novel structure currently under clinical studies in various neoplastic diseases, has revealed significant in vitro activity against chloroquine-resistant (FCB, FTA, FVO) and sensitive (FSL, FUI, FH) strains of Plasmodium falciparum. Inhibition of the growth and maturation of parasites after 36-h exposures to Spirogermanium started at concentrations ranging from 2.48 to 9.9 nM/ml. These concentrations appear to be within the range of Spirogermanium plasma levels reported in clinical studies with this drug. Since its clinical toxicities are unusually low in comparison with other anticancer drugs, our results on its in vitro activity against Plasmodium falciparum indicate Spirogermanium is an antimalarial drug of entirely novel structure, active in resistant strains.

Antimalarials↗
PubMed1982

Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum.

Plasmodium falciparum trophozoites were isolated by mechanical rupture of infected human erythrocytes followed by a series of differential centrifugation steps. After lysis with sonication, the 100 000 x g supernatant of parasites and uninfected host cells was used to determine the specific activities of a number of enzymes involved in purine and pyrimidine metabolism. P. falciparum possessed the purine salvage enzymes: adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyltransferase (PRTase), xanthine PRTase, adenine PRTase, adenosine kinase. The last two enzymes, however, were present at much lower activity levels. Hypoxanthine was converted (presumably via IMP) into adenine and guanine nucleotides only in the presence both of supernatant and membrane fractions of P. falciparum. Two enzymes involved in the de novo synthesis of pyrimidines, orotic acid PRTase, and orotidine 5'-phosphate decarboxylase, were present in parasite extracts as were the enzymes for pyrimidine nucleotide phosphorylation: UMP-CMP kinase, dTMP kinase, nucleoside diphosphate kinase. Xanthine oxidase, CTP synthetase, cytidine deaminase and several kinases for the salvage of pyrimidine nucleosides were not detected in the parasites. Both phosphoribosyl pyrophosphate synthetase and uracil PRTase were present but at low activity levels. Human erythrocytes displayed similar but not identical enzyme patterns. Enzyme specific activities, however, were generally much lower than those of the corresponding parasite enzymes.

Adenosine Deaminase↗
PubMed1979

In vitro inhibition of the growth of Plasmodium falciparum by Aotus serum.

An in vitro assay for measuring growth and reinvasion inhibition of Plasmodium falciparum was developed from a microculture system. Inhibition of growth was observed after parasites had been incubated with Aotus serum obtained from monkeys that had become immune to malaria after repeated exposure to P. falciparum. Immune Aotus serum (IAS), at concentrations as low as 1.25%, showed a marked inhibitory effect upon parasites cultured in 10% normal human serum (NHS). Growth was also inhibited when 5% of normal Aotus serum (NAS) was added to medium containing 10% of NHS. The inhibitory activity of NAS, but not of IAS, could be removed by lowering serum concentrations below 2.5% or by exposing the serum to 56 degrees C for 30 minutes. Further investigations with relatively synchronous microcultures showed that (3)H-hypoxanthine, a nucleic acid precursor, was incorporated preferentially into the more mature parasites of P. falciparum. Additional studies with the microculture system should elucidate the effects of immune serum on different asexual erythrocyte stages and, in general, facilitate the study of immune effector mechanisms in falciparum malaria.

Animals↗
PubMed1979

Concentration and separation of erythrocytes infected with Plasmodium falciparum by gradient centrifugation.

Concentration of infected erythrocytes was achieved in cell suspensions derived from long-term culture of Plasmodium falciparum growing asynchronously in human erythrocytes. This new procedure involves the slow centrifugation (at 33 g) of erythrocyte suspensions through 5% Ficoll solutions. Mature asexual erythrocytic forms are preferentially retained in the gradient solution (top fraction). After further gradient centrifugation of these parasitized cells, the concentration of mature forms is increased 15- to 31-fold and a mature form parasitaemia of 71-81% is obtained in the final erythrocyte suspension. Furthermore, at least 75% of the total number of the mature forms can be retrieved by this method. Parasitized cells that are not retained in the gradient are sedimented to the bottom of the tube (bottom fraction) and consist predominantly of ring forms. Parasites from both the top and bottom fractions are viable and have been used to initiate short-term synchronous cultures. By providing purified parasite preparations, this simple procedure will facilitate immunological, chemotherapeutic, and biochemical studies with P. falciparum.

Cell Separation↗
PubMed1979

Harvest of Plasmodium falciparum merozoites from continuous culture.

Spontaneously released merozoites were harvested from cultures in which 42-90% of the erythrocytes had been infected with mature forms of Plasmodium falciparum at the start of incubation. The mature forms had been extracted from asynchronous cultures by the use of Ficoll and Plasmagel gradients. As the mature forms consisted of both trophozoites and schizonts, merozoites were released into the culture medium over a long period of time. The synchrony of merozoite release did not appear to be improved by prior exposure of parasites to sorbitol. Over this prolonged period of incubation, the yield of merozoites was disappointingly low in cultures containing 2.5% of erythrocytes. At erythrocyte concentrations of 0.01-0.25%, 3-10 times more merozoites were released into the medium; 0.4-2.3 merozoites per initial mature form were harvested over a 15-19-hour period. In addition to merozoites, contents of the culture medium included intact erythrocytes, ghost cells, and other cellular fragments. Only intact erythrocytes were effectively removed from the medium by simple or Ficoll gradient centrifugation. Merozoite preparations that are free from host cellular material are important in the development of a human malaria vaccine.

Animals↗