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multilocus isozyme identification of trypanosoma brucei stocks isolated in central africa: evidence for an animal reservoir of sleeping sickness in congo.six congolese and 3 zairian trypanosoma brucei stocks were studied by isozyme cellulose acetate electrophoresis. twenty isozyme systems were used, of which only 5 showed variability. these 5 polymorphic systems made it possible to identify 5 different zymodemes. zymodemes isolated from man were recorded both from pig and sheep too, which confirms the results of previous authors. this favors the existence of an animal reservoir of human african trypanosomiasis in the congo, which could play a rol ...19911680279
elevation of the concentration of acute phase proteins in dogs infected with trypanosoma brucei.plasma concentrations of the acute phase proteins (app), c-reactive protein (crp) and haptoglobin (hp), increased markedly following experimental infection of dogs with trypanosoma brucei. the highest concentrations of crp were observed immediately after peaks of parasitaemia. treatment with curative doses of the trypanocidal drug suramin caused a rapid decrease in crp. relapse infections after subcurative treatment were followed by a reappearance of high plasma crp concentrations. haptoglobin r ...19911680282
the effect of verapamil alone and in combination with trypanocides on multidrug-resistant trypanosoma brucei brucei.following previous studies of verapamil reversal of multidrug resistance in cancer cells and chloroquine resistance in malaria, the effect of the calcium channel blocker verapamil was investigated on multidrug-resistant and susceptible trypanosoma brucei brucei. resistance of cloned parasites to diminazene aceturate (berenil) and isometamidium chloride (samorin) was expressed in a cell-free in vitro culture system. verapamil showed antitrypanosomal activity against both, multidrug-resistant and ...19911685302
hybrid formation between african trypanosomes in vitro. 19911685305
biochemical properties of histone-like proteins of procyclic trypanosoma brucei brucei.four histone-like proteins a, b, c, d were extracted with 0.2 m h2so4 from soluble nuclear chromatin of trypanosoma brucei brucei procyclic culture forms and purified by fplc reversed phase chromatography. the amino acid composition of these proteins and their electrophoretic mobilities in three different gel systems strongly indicated their core histone nature. similarities were found between a, b, c and d with the core histones h3, h2a, h2b and h4 of higher eukaryotes, respectively. on the oth ...19911685873
use of antigen-detection enzyme immunoassays in assessment of trypanotolerance in n'dama cattle.antigen-detection enzyme immunoassays (elisa) were used for the diagnosis of trypanosoma vivax, t. congolense and t. brucei in n'dama cattle in gabon, central africa. the assays are based on monoclonal antibodies which recognise trypanosome antigens specific for each of the three species and animals were termed 'antigenaemic' when found positive by this technique but not found parasitaemic by the buffy coat technique. 148 one-year-old animals were exposed to a medium natural tsetse challenge and ...19911686140
surface coat synthesis and turnover from epimastigote to bloodstream forms of trypanosoma brucei.monoclonal antibodies to metacyclic surface coat glycoproteins of trypanosoma brucei brucei stib 247lg were produced for a study of the synthesis of metacyclic variable surface glycoproteins (vsgs) within the salivary gland of glossina morsitans morsitans, and of the first exchange of the surface glycoproteins after infection in mice. immunofluorescence antibody tests and protein a-gold labelling revealed that the vsgs are continuously integrated into the whole surface of the trypanosome while i ...19911686146
trypanosoma brucei: peptide mapping of partially homologous variable surface glycoproteins.antigenic variation in trypanosoma brucei is caused by amino acid sequence changes in a major surface glycoprotein. each trypanosome may contain between 100 and 1000 genes coding for this glycoprotein. some of these genes are members of partially homologous gene families. in addition, segments of different genes may combine to form 'hybrid' or 'mosaic' genes. thus, surface glycoproteins exist containing varying amounts of amino acid sequence homology. for investigations of molecular mechanisms o ...19911743853
the trypanosoma brucei dna polymerase alpha core subunit gene is developmentally regulated and linked to a constitutively expressed open reading frame.as an initial step towards the characterization of replicative dna polymerases of trypanosomes, we have cloned, sequenced and examined the expression of the trypanosoma (trypanozoon) brucei brucei gene that encodes the dna polymerase alpha catalytic core (pol alpha). the protein sequence contains the six conserved regions that have been recognized previously in eukaryotic and viral replicative dna polymerases. in addition, we have identified a seventh region which appears to be conserved primari ...19911754381
the distribution of permeant ions demonstrates the presence of at least two distinct electrical gradients in bloodstream forms of trypanosoma brucei.the distribution of 86rb+ and the radiolabelled lipophilic cation [3h]methyltriphenylphosphonium (meph3p+) was used to investigate the membrane potentials that exist in bloodstream forms of trypanosoma brucei. even after correction for binding to cellular constituents, the accumulation of meph3p+ was approximately tenfold greater than the accumulation of rb+ under resting conditions. the addition of low concentrations of carbonylcyanide p-trifluoromethoxyphenylhydrazone or valinomycin reduced th ...19911761044
high homology between variant surface glycoprotein gene expression sites of trypanosoma brucei and trypanosoma gambiense.the antat 11.17 variant surface glycoprotein (vsg) is synthesized in both metacyclic and bloodstream forms of trypanosoma gambiense. we have characterized the antat 11.17 gene, and analyzed its expression site (es) in the bloodstream form by southern and northern blotting with probes from the trypanosoma brucei antat 1.3a vsg es, and by run-on transcription. the antat 11.17 es is located at the end of a 700-kb chromosome. it appears to contain all the genes (esags, for expression site-associated ...19911762631
porcine trypanosomosis in nigeria: infections in local and exotic pigs in the nsukka area of anambra state.a twelve-month survey in three local government areas (lga) in nsukka zone, anambra state, nigeria revealed that out of 150 local and exotic breeds of pig examined, 46 (30.7%) were infected with trypanosomes. both single and mixed infections of trypanosoma brucei and t. congolense were observed. however, t. brucei was the predominant trypanosome encountered. the husbandry system in practice was the most significant factor influencing the prevalence of trypanosomes in the pigs. in addition signif ...19911763434
trypanosomiasis in different breeds of cattle from benin.blood of different breeds of cattle, namely lagune from the atlantic province, borgou and borgou x zebu from the borgou province, and somba and zebu from the atacora province of benin, were examined for trypanosome infection. thick and thin blood smears for trypanosomes, the card agglutination test (catt), indirect immunofluorescent antibody test (ifat) and trypanolytic test for antibodies to trypanosomes were used. trypanosomes were detected in 19.3% (range 9.8-31.4%) of animals by examination ...19911763478
control of tsetse and trypanosomiasis transmission in uganda by applications of lambda-cyhalothrin.the pyrethroid insecticide lambda-cyhalothrin was evaluated in field trials against glossina f.fuscipes and sleeping sickness transmission in iyolwa sub-county, tororo district, uganda. the insecticide was applied selectively to the resting-sites of tsetse, by bush-spraying, using 10% wettable powder (10wp) formulation at an application rate of 11.6 g a.i./ha over an area of 28 km2, or by a 2% electrodyn formulation (2ed) applied at 0.9 g a.i./ha over 30 km2. in a third trial area of 32 km2, 215 ...19911768891
lectin and peritrophic membrane development in the gut of glossina m.morsitans and a discussion of their role in protecting the fly against trypanosome infection.newly emerged glossina m.morsitans westwood tsetse flies lack a peritrophic membrane which develops to fully line the midgut after c. 80-90 h. midgut lectins are mainly associated with the peritrophic membrane. lectin levels in the blood-free gut of adult flies rise slowly up to 8 days and then rapidly to at least 14 days post-eclosion (when the last of our recordings was made). despite starving flies for 4 days prior to the agglutination assay, gut lectin levels in older flies are 100-200 times ...19911773127
fever, leukopenia, and a cutaneous lesion in a man who had recently traveled in africa. 19911775846
treatment of experimental trypanosomiasis in pigs.the therapeutic activity of difluoromethylornithine (dfmo), diminazene aceturate (berenil) and their combination against chronic trypanosomiasis was investigated in experimental trypanosoma brucei brucei infections of growing pigs. dfmo (300 mg/kg/day orally for 10 days), diminazene aceturate (7 mg/kg in single intramuscular injection) and a combination of the two agents at the above dosages produced varied periods of aparasitaemia in the treated pigs. relapse parasitaemia occurred in all treatm ...19911777799
subcellular distribution of trypanothione reductase in bloodstream and procyclic forms of trypanosoma brucei. 19911779986
the effects of genetic exchange on variable antigen expression in trypanosoma brucei.the inheritance of variant surface antigens in trypanosoma brucei has been determined by identifying variable antigen types (vats) in each of two cloned parental stocks and then examining the presence and abundance of these vats in hybrid progeny produced when these stocks undergo genetic exchange during co-transmission through tsetse flies. nine vats have been identified from the repertoire of the parental stock stib 247l and 5 vats have been identified from the parental stock stib 386aa; the i ...19911780175
trypanosoma brucei brucei: differences in the trypanocidal activity of human plasma and its relationship to the level of high density lipoproteins.although high density lipoprotein (hdl) particles purified from human serum by ultracentrifugation are known to lyse trypanosoma brucei brucei, it is unclear whether individual differences in the trypanocidal activity of human serum reflect changes in the concentration of hdl per se. in the present study, trypanolytic activity, whether assessed in vitro or in vivo, was greater with plasma from normal healthy individuals than with plasma from patients with various hepatic diseases and associated ...19911780989
transferrin receptor, antigenic variation and the prospect of a trypanosome vaccine. 19911781026
evolutionary aspects of gpi metabolism in kinetoplastid parasites.there is a growing, but still very patchy, data base of gpi structure, biosynthesis and function. in this article we speculate freely on the function of gpi anchors, and the origins of gpi-related molecules, primarily with reference to the protozoan parasites trypanosoma brucei and the leishmania. the views expressed draw on fairly wild extrapolations and some will, no doubt, not stand the tests of time. several of the hypotheses presented should therefore be taken with a pinch of salt, some lem ...19911782666
transferrin is a growth factor for the bloodstream form of trypanosoma brucei.a method for the selective depletion of transferrin from bovine serum is presented. bloodstream forms of trypanosoma brucei cannot grow in medium containing transferrin-deficient serum, whereas reconstitution with transferrin restores normal growth. we conclude that transferrin is an essential growth factor for the mammalian stage of the parasite.19911792224
preparation of phenylalanine-deuterated, and totally 15n-enriched, calmodulins from trypanosoma brucei, and its application to drug binding studies. 19911794549
chemotherapy of cns-trypanosomiasis: combination chemotherapy with a 5-nitroimidazole (mk 436), an arsenical (cymelarsan) and suramin.a detailed study of the combined effect of suramin, mk 436 (5-nitroimidazole) and cymelarsan (melaminylthioarsenate) was investigated in the murine cns-trypanosomiasis model. using a combination of cymelarsan and mk 436 without preliminary suramin, complete cures were obtained with a 2 day treatment of 15.0 mg/kg mk 436 and 5.0 mg/kg cymelarsan. if the mk 436 was reduced to 10 mg/kg then 4 consecutive daily treatments were required. if the cymelarsan was reduced to 2.5 mg/kg either a 3 day treat ...19911801135
laboratory diagnosis of trypanosomiasis.although african trypanosomiasis, or sleeping sickness, in humans was largely under control approximately 30 years ago, today most of the historical foci show an alarming increase in the number of cases, particularly those in east and central africa. this article describes the epidemiology, clinical features, and diagnostic techniques for both african and american trypanosomiasis.19911802527
a soluble fumarate reductase in trypanosoma brucei procyclic trypomastigotes.the enzyme nadh-fumarate reductase associated with the membrane fraction of trypanosoma brucei procyclic trypomastigotes, can be solubilized by more than 50% when increasing the ionic strength to the equivalent of 150 mm kcl. the apparent kms for nadh (125 microm) and fumarate (50 microm) remain close to those previously reported for the membrane-bound form of this enzyme. other electron acceptors (i.e. oxygen or cytochrome c) appear to accept electrons in the absence of fumarate (km for cytochr ...19911818198
pig trypanosomiasis: comparative anaemia and histopathology of lymphoid organs.anaemia with characteristic clinical symptoms, haematological changes and histopathology of lymphoid organs, was observed following experimental infection of pig with pathogenic species of trypanosoma brucei brucei and trypanosoma congolense, the former being more virulent than the latter. mean incubation periods were 4 and 7 days, and generalized fluctuating levels of parasitaemia and pyrexia without mortality were observed. other symptoms included hyperaemia, petechial haemorrhages leading to ...19911824133
pathogenicity of trypanosoma brucei brucei in experimentally infected pigs.an experimental infection of 4-to 5-month old pigs with a stock of trypanosoma brucei brucei resulted in a high parasitaemia, anorexia, pyrexia and a decline in the packed cell volume by one third. nervous sign of circling and wobbling of the hind legs occurred in one of the pigs which at necropsy revealed a very severe meningo-encephalitis and the presence of trypanosomes in the brain. these results confirm that t. b. brucei might cause a severe disease in pigs.19911824136
a new u6 small nuclear ribonucleoprotein-specific protein conserved between cis- and trans-splicing systems.spliceosomal u6 small nuclear rna (snrna) plays a central role in the pre-mrna splicing mechanism and is highly conserved throughout evolution. previously, a sequence element essential for both capping and cytoplasmic-nuclear transport of u6 snrna was mapped in the 5'-terminal domain of u6 snrna. we have identified a protein in cytoplasmic extracts of mammalian and trypanosoma brucei cells that binds specifically to this u6 snrna element. competition studies with mutant and heterologous rnas dem ...19911826044
maintenance of internal ph and an electrochemical gradient in trypanosoma brucei.the internal ph value (phi) of the long-slender bloodstream form of trypanosoma brucei was estimated from the distribution of 14c-labeled 5,5-dimethyl-2,4-oxazolidinedione or 14c-labeled methyl amine between the intracellular space of the cells and the medium. the phi of t. brucei remained relatively constant at 7.0-7.2 throughout an extracellular ph (pho) range of 6.0-8.0. the maintenance of an internal ph more acidic than the environment appears to be a unique feature. preincubation of t. bruc ...19911826655
defective glycosyl phosphatidylinositol biosynthesis in extracts of three thy-1 negative lymphoma cell mutants.the glycosyl phosphatidylinositol (gpi) anchors that attach certain proteins to membranes are preassembled by sequential addition of glycan components to phosphatidylinositol (pi) before being transferred to nascent polypeptide. a cell-free system consisting of trypanosome membranes has been reported to catalyze gpi biosynthesis (masterson, w. j., doering, t. l., hart, g. w., and englund, p. t. (1989) cell 56, 793-800; menon, a. k., schwarz, r. t., mayor, s., and cross, g. a. m. (1990) j. biol. ...19911828068
transfer of glycosyl-phosphatidylinositol membrane anchors to polypeptide acceptors in a cell-free system.glycosylinositol phospholipid (gpi) membrane anchors are the sole means of membrane attachment of a large number of cell surface proteins, including the variant surface glycoproteins (vsgs) of the parasitic protozoan, trypanosoma brucei. biosynthetic data suggest that gpi-anchored proteins are synthesized with carboxy-terminal extensions that are immediately replaced by gpi, suggesting the existence of preformed gpi species available for transfer to the nascent protein in the er. candidate precu ...19911828808
an analog of myristic acid with selective toxicity for african trypanosomes.trypanosoma brucei, the protozoan parasite responsible for african sleeping sickness, evades the host immune response through the process of antigenic variation. the variant antigen, known as the variant surface glycoprotein (vsg), is anchored to the cell surface by a glycosyl phosphatidylinositol (gpi) structure that contains myristate (n-tetradecanoate) as its only fatty acid component. the utilization of heteroatom-containing analogs of myristate was studied both in a cell-free system and in ...19911829548
mannosamine, a novel inhibitor of glycosylphosphatidylinositol incorporation into proteins.mannosamine (2-amino-2-deoxy d-mannose) is shown here to block the incorporation of glycosylphosphatidylinositol (gpi) into gpi-anchored proteins. the amino sugar drastically reduced the surface expression of a recombinant gpi-anchored protein in polarized mdck cells, converted this apical membrane-bound protein to an unpolarized secretory product and blocked the expression of endogenous gpi-anchored proteins. furthermore, it specifically inhibited the incorporation of [3h]ethanolamine (a gpi co ...19911829673
phenylmethanesulphonyl fluoride inhibits gpi anchor biosynthesis in the african trypanosome.a wide variety of eukaryotic membrane proteins are anchored to the outside of cells by covalent linkage to glycosyl phosphatidylinositol (gpi). one of the best characterized examples is the variant surface glycoprotein (vsg) of the protozoan parasite, trypanosoma brucei. the structure of the gpi precursor is ethanolamine-po4-man alpha 1-2man alpha 1-6man alpha 1-4glcnh2-pi; the phosphoethanolamine moiety forms an amide linkage to the vsg polypeptide alpha-cooh group during its attachment to prot ...19911829674
evolutionary conservation of a microbody targeting signal that targets proteins to peroxisomes, glyoxysomes, and glycosomes.peroxisomes, glyoxysomes, glycosomes, and hydrogenosomes have each been classified as microbodies, i.e., subcellular organelles with an electron-dense matrix that is bound by a single membrane. we investigated whether these organelles might share a common evolutionary origin by asking if targeting signals used for translocation of proteins into these microbodies are related. a peroxisomal targeting signal (pts) consisting of the cooh-terminal tripeptide serine-lysine-leucine-cooh has been identi ...19911831458
the mitochondrial atp synthase of trypanosoma brucei: developmental regulation through the life cycle.the mitochondrial h(+)-atpase of the parasitic protozoan trypanosoma brucei is shown to be developmentally regulated through the t. brucei life cycle as has been shown for components of the mitochondrial electron transport chain. we have substantiated our results by assaying not only for oligomycin-sensitive atpase activity but also by determining the level of atp synthetic activity. these results show that the level of atpase present in the procyclic form of t. brucei is increased by at least t ...19911832842
structure and transcription of a p-atpase gene from trypanosoma brucei.a putative atpase gene was cloned from trypanosoma brucei genomic dna. the length of the gene open reading frame is 3,033 bp, predicting a protein of about 110 kda. the sequence of this protein shares 10 blocks of homology with other eukaryotic atpases, including the putative phosphorylation site characteristic of p-atpases. its hydropathy profile reveals 8-10 potential membrane-spanning regions. while the amino acid sequence of the t. brucei atpase shows only 25% overall homology with its count ...19911833643
affinity purification of trypanosoma brucei small nuclear ribonucleoproteins reveals common and specific protein components.we have developed a procedure for the affinity purification of small nuclear ribonucleoproteins (snrnps) of trypanosoma brucei (u2 and u4/u6 snrnps), which are essential for trans splicing. each of these snrnps can be specifically and efficiently selected from t. brucei extracts through biotinylated antisense 2'-o-methylated rna oligonucleotides immobilized on streptavidin-agarose. protein analysis revealed a set of five low molecular weight polypeptides common to the u2 and u4/u6 snrnps and the ...19911833773
production of monoclonal antibodies against the purified glycosylphosphatidylinositol anchor of the variant surface glycoprotein from trypanosoma brucei brucei.the glycosylphosphatidylinositol anchor (gpi) from the membrane form variant surface glycoprotein (mfvsg) of trypanosoma brucei brucei was isolated and identified after radioactive labeling with [3h]myristic acid, by immunostaining on hptlc with a polyclonal antibody directed against mfvsg and by negative ion laser desorption and fast atom bombardment mass spectrometry of the gpi anchor before and after peracetylation. for the production of monoclonal antibodies the purified gpi molecule was inc ...19911834019
differential expression of the oligomycin-sensitive atpase in bloodstream forms of trypanosoma brucei brucei.we report the differential expression of the oligomycin-sensitive mitochondrial atpase in pleomorphic bloodstream forms of trypanosoma brucei brucei as observed with enzymatic assays and electron microscope histochemistry. as the cells differentiate from long slender to short stumpy forms, total specific activity of the mitochondrial atpase in a crude mitochondrial fraction doubles and the oligomycin-sensitive specific activity increases 5-fold. upon in vitro differentiation to procyclic forms, ...19911838138
the biology of the glycosylphosphatidylinositol-specific phospholipase c of trypanosoma brucei. 19911838304
anatomy of the parp gene promoter of trypanosoma brucei.while growing in the tsetse fly, trypanosoma brucei expresses a major surface glycoprotein, the procyclic acidic repetitive protein (parp). the parp genes are transcribed by an alpha-amanitin-resistant rna polymerase. we have determined the sequence requirements for parp promoter activity. studies of rna produced from input dna in transiently transfected trypanosomes indicate that the rna is correctly processed by trans-splicing and polyadenylation. deletion analyses show that 330 bp are suffici ...19911840521
[vectorial capacity of glossina palpalis gambiensis (bobo dioulasso) for trypanosoma brucei brucei eatro 1125].a total of 440 teneral glossina palpalis gambiensis received one single bloodmeal on a guinea pig infected chronically with trypanosoma brucei brucei eatro 1125. metacyclic infections were present in 11.29% of the flies, in 2.32% infections were limited to procyclical stages. no significant difference in vectorial capacity was observed between male and female flies, the level of metacyclic infections being 13.19% in the former and 9.55% in the latter. the parasitaemia level, the percentage of st ...19911843825
dl-alpha-difluoromethylornithine (dfmo)-berenil combination: therapeutic and prophylactic activity against trypanosoma brucei brucei infection in mice.the therapeutic and prophylactic activity of difluoromethylornithine (dfmo) (2% in drinking water for 4 days) and berenil (7 mg/kg live weight intraperitoneally) combination was investigated in mice infected with trypanosoma brucei brucei. using a previously described mouse model of the african trypanosomosis of the central nervous system, it was demonstrated that the combination was curative and acted synergistically. however, if used prophylactically it had no advantage over berenil alone.19911843826
a transferrin-binding protein of trypanosoma brucei is encoded by one of the genes in the variant surface glycoprotein gene expression site.a transferrin-binding protein (tfbp) with an apparent molecular weight of 42 kd was purified from detergent-soluble membrane proteins of bloodstream forms of trypanosoma brucei. the protein is not expressed in the insect-borne stage of the parasite's life-cycle. purified tfbp can be converted from an amphiphilic to a hydrophilic form by cleavage with t.brucei glycosylphosphatidylinositol (gpi)-specific phospholipase c, demonstrating that the c-terminus is modified by a gpi-membrane anchor. the t ...19911845367
differential sensitivity of trypanosoma brucei rhodesiense isolates to in vitro lysis by arsenicals.clinical isolates of trypanosoma brucei rhodesiense, which were resistant to arsenical drugs in murine infections, were examined for resistance in vitro. a rapid lysis assay was developed which was able to predict in vivo sensitivity to melarsoprol (mel b, arsobal) and melarsen oxide. the assay was based on the finding that long slender bloodforms of drug-sensitive isolates would lyse in the presence of arsenicals upon incubation in heat-inactivated fetal bovine serum. on the basis of plots of d ...19911849084
developmental variation of glycosylphosphatidylinositol membrane anchors in trypanosoma brucei. identification of a candidate biosynthetic precursor of the glycosylphosphatidylinositol anchor of the major procyclic stage surface glycoprotein.the major surface antigen of the mammalian bloodstream form of trypanosoma brucei, the variant surface glycoprotein (vsg), is attached to the cell membrane by a glycosylphosphatidylinositol (gpi) anchor. the vsg anchor is susceptible to phosphatidylinositol-specific phospholipase c (pi-plc). candidate precursor glycolipids, p2 and p3, which are pi-plc-sensitive and -resistant respectively, have been characterized in the bloodstream stage. in the insect midgut stage, the major surface glycoprotei ...19911850744
a phosphoglycerate kinase-like molecule localized to glycosomal microbodies: evidence that the topogenic signal is not at the c-terminus.the phosphoglycerate kinase (pgk) gene complex of trypanosoma brucei contains three tandemly linked related genes. one gene encodes a cytoplasmic pgk, while another encodes a pgk isozyme localized to glycosomal microbodies. in this communication, we report that the third gene in this complex encodes a 56-kda molecule which is also localized to the glycosomal core. dna sequence analysis indicates that this gene contains multiple substitutions and a large insertion in the amino domain, but that it ...19911852165
variant surface glycoprotein from trypanosoma brucei clone ytat 1.1 contains a latent calmodulin-binding domain.calmodulin affinity chromatography and chromatofocusing were used to purify calmodulin-binding proteins of 32-40-kda from homogenates of trypanosoma brucei clone ytat1.1. the trypanosome proteins associated with calmodulins from different sources and reversibly inhibited calmodulin-dependent bovine brain phosphodiesterase. purified 32-kda protein bound to calmodulin with an approximate kd of 1.3 nm. polyclonal antibodies directed against purified 32-kda protein and monoclonal antibody eca6 recog ...19911852168
comparative study on rickettsia-like organisms in the midgut epithelial cells of different glossina species.the midgut epithelium of glossina morsitans centralis, g. austeni, g. pallidipes, g. palpalis palpalis, g. p. gambiensis, g. fuscipes fuscipes, g. tachinoides and g. brevipalpis from ilrad-bred colonies was examined, by electron microscopy, for the presence and distribution of rickettsia-like organisms (rlos). rlos were present in the midgut epithelial cells of all non-teneral tsetse. in g.m. centralis, g. pallidipes and, to a much lesser extent, g. brevipalpis, rlos were numerous and were prese ...19911852486
rickettsia-like organisms, puparial temperature and susceptibility to trypanosome infection in glossina morsitans.maintaining the puparial stage of successive generations of a population of tsetse 3 degrees c lower than normal reduced the numbers of rickettsia-like organisms (rlo) carried by emerging flies. the susceptibility of these flies to midgut infection with trypanosoma congolense was also significantly reduced compared with control flies held at normal temperature. these results support the view that the relationship between rlo and susceptibility is quantitative-teneral flies with heavier rlo infec ...19911852487
diagnosis of human african trypanosomiasis and visceral leishmaniasis based on the detection of anti-parasite-enzyme antibodies.a sensitive diagnostic assay for parasitic infections based on the detection of anti-enzyme antibodies is presented. all serum antibodies produced in response to parasite antigens are immobilized via their fc domain on matrix-bound protein g. incubation of the immobilized antibodies with saturating amounts of parasite extract results in the binding of all recognized antigens, including those directed against a specific and readily measurable enzyme. the amount of bound enzyme is proportional to ...19911856492
role of phospholipids in the cytotoxic action of high density lipoprotein on trypanosomes.host range among the african trypanosomes, protozoa that cause fatal diseases both in humans and livestock, may be, in part, regulated by toxic properties associated with host high density lipoproteins (hdl). high density lipoproteins from hosts resistant (baboon, human) or susceptible (rabbit, rat) to trypanosoma brucei infection were isolated and their trypanocidal activity was determined in in vitro cell lysis assays. rabbit and rat hdl were not cytotoxic while baboon and human hdl rapidly ly ...19911856609
kinetic properties of fructose bisphosphate aldolase from trypanosoma brucei compared to aldolase from rabbit muscle and staphylococcus aureus.the kinetic properties of aldolase from trypanosoma brucei were studied in comparison with aldolase from rabbit muscle and staphylococcus aureus. the 3 enzymes displayed a similar broad ph optimum for the cleavage of fructose 1,6-bisphosphate (fru(1,6)p2) and a similar narrow ph optimum for the cleavage of fructose 1-phosphate (fru-1-p). however, small alterations in the maximal cleavage rate at more extreme ph values yielded disparities between the ph curves. the reaction catalyzed by the aldol ...19911857377
chemical modification of fructose bisphosphate aldolase from trypanosoma brucei compared to aldolase from rabbit muscle and staphylococcus aureus.chemical modifications of class i aldolases from trypanosoma brucei, rabbit muscle and staphylococcus aureus with carboxypeptidase a, glyceraldehyde 3-phosphate and cysteine-specific reagents revealed the following differences between the three homologous enzymes. aldolase from s. aureus was not affected by any of these reagents. carboxypeptidase-a treatment of rabbit-muscle and t. brucei aldolase inhibited the activity of both enzymes towards fructose-1,6-bisphosphate (fru(1,6)p2), while the ac ...19911857380
characterization of a novel developmentally regulated gene from trypanosoma brucei encoding a potential phosphoprotein.we have isolated a cdna clone corresponding to a single-copy nuclear gene that is upregulated at the mrna level during in vitro differentiation of bloodstream trypomastigotes of strains of both trypanosoma brucei brucei and trypanosoma brucei rhodesiense to procyclic forms. transcript levels begin to increase within minutes of introduction of bloodstream forms into culture and peak well before cultures exhibit a procyclic morphology. this increase in transcript levels was found to occur both in ...19911857381
characterization of pyruvate kinase of trypanosoma brucei and its role in the regulation of carbohydrate metabolism.pyruvate kinase from trypanosoma brucei is a labile enzyme, losing its activity within several hours. in mixtures containing 50 mm triethanolamine buffer, ph 7.2, 25% glycerol and 0.5 mm inorganic phosphate the enzyme remained active and could be purified to homogeneity with a specific activity of 417 units mg-1 and a yield of 65%. the enzyme has an activation energy of 31.9 kj mol-1. magnesium and potassium ions are essential for activity. cobalt or manganese ions replace mg2+ but this leads to ...19911857383
differences in glucose transport between blood stream and procyclic forms of trypanosoma brucei rhodesiense.in african trypanosomes the requirements for glucose and its metabolism vary in different stages of the life cycle. here we present evidence that cultured procyclic trypanosomes of trypanosoma brucei rhodesiense uptake glucose against a concentration gradient in a time and dose-dependent manner. moreover, glucose transport is completely inhibited by the sulphydryl inhibitor n-ethylmaleimide, suggesting the presence of a protein moiety as the carrier molecule. comparison of glucose uptake in bloo ...19911857387
sequence of a trna gene cluster in trypanosoma brucei. 19911861987
the cytoskeletal architecture of trypanosoma brucei.the cytoskeleton of trypanosoma brucei has been analyzed by the high-resolution technique of quick-freeze deep-etch rotary-shadowing electron microscopy. the study provides detailed structural information on the subpellicular array of microtubules, the flagellum, and the interaction of these 2 major structures of the trypanosomal cytoskeleton with each other. the subpellicular microtubules closely interact both with the cell membrane and with each other. at the anterior tip of the cell they conv ...19911865269
diminazene aceturate residues in the tissues of healthy, trypanosoma congolense and trypanosoma brucei brucei infected dogs.the tissue distribution and residue profile of diminazene aceturate was investigated in healthy dogs and in dogs infected with trypanosoma congolense and trypanosoma brucei brucei. the drug was administered at 3.5 mg/kg i.m. and tissue samples were taken post mortem from the animals at 48, 72, 120, 168 and 240 h after injection. the drug was distributed to various organs and tissues of the body with the highest concentrations occurring in liver and kidney. higher drug levels were obtained in the ...19911868320
the glycosomes of trypanosomes: number and distribution as revealed by electron spectroscopic imaging and 3-d reconstruction.computer-aided 3-d reconstruction of trypanosomes from 0.35-micron-thick sections imaged on the zeiss 902 electron microscope are being used to study the dynamics of cell organization. segregation of glycolytic enzymes into glycosomes raises questions concerning the distribution and biogenesis of these organelles. direct counts of glycosomes from trypanosoma evansi indicate 30-40 per cell and for the closely related t. brucei, 65 per cell. these figures contrast with the estimates of others who ...19911870115
comparative histochemical studies of rats infected with a pathogenic and nonpathogenic trypanosome.histochemical variations in tissues from rats inoculated with trypanosoma lewisi and trypanosoma rhodesiense were investigated. during peak parasitemia, the liver of rats inoculated with t lewisi showed increased glycogen distribution. however, glycogen depletion was noted in the liver and spleen of animals inoculated with living cells of t rhodesiense. depletion was very apparent from day 4 to day 10. throughout the period of observation, only a small amount of lipid infiltration occurred in ti ...19911875425
basal body movements as a mechanism for mitochondrial genome segregation in the trypanosome cell cycle.the mitochondrial genome of trypanosoma brucei is organized in the form of a complex catenated network of circular dna molecules. this mass of dna, known as the kinetoplast, is present at a unique site in the single mitochondrion, and is replicated in a discrete, periodic s phase of the cell cycle. the single-copy nature of the kinetoplast suggests that there is a mechanism ensuring segregation fidelity of replicated copies to each daughter cell. historically, speculation regarding the nature of ...19911876188
molecular cloning and analysis of two tandemly linked genes for pyruvate kinase of trypanosoma brucei.in trypanosoma brucei (stock 427) genes encoding the glycolytic enzyme pyruvate kinase are present on two homologous chromosomes. we have cloned and characterized one of the alleles. two large, tandemly arranged open reading frames were found, each coding for a pyruvate kinase polypeptide of 498 amino acids. the gene sequences differ at 15 positions, resulting in five amino acid substitutions. the calculated molecular masses of the polypeptides are 54,378 da and 54,363 da. these values are somew ...19911879424
the effects of the methylating agent 1,2-bis(methylsulfonyl)-1-methylhydrazine on morphology, dna content and mitochondrial function of trypanosoma brucei subspecies.repeated exposure of trypanosomes in vitro or in vivo to low concentrations of the methylating agent 1,2-bis(methylsulfonyl)-1-methylhydrazine induces a series of moderately synchronous morphological and biochemical changes. cell division halts and the long-slender bloodstream forms transform to short-stumpy forms via larger intermediate-stage cells which contain approximately double the normal g2 content of dna. in common with naturally occurring short-stumpy trypanosomes, drug-induced short-st ...19911880758
refined 1.83 a structure of trypanosomal triosephosphate isomerase crystallized in the presence of 2.4 m-ammonium sulphate. a comparison with the structure of the trypanosomal triosephosphate isomerase-glycerol-3-phosphate complex.triosephosphate isomerase (tim) is a dimeric glycolytic enzyme. tim from trypanosoma brucei brucei has been crystallized at ph 7.0 in 2.4 m-ammonium sulphate. the well-diffracting crystals have one dimer per asymmetric unit. the structure has been refined at 1.83 a resolution with an r-factor of 18.3% for all data between 6 a and 1.83 a (37,568 reflections). the model consists of 3778 protein atoms and 297 solvent atoms. subunit 1 is involved in considerably more crystal contacts than subunit 2. ...19911880808
elusive trypanosomes.professor kershaw's encouragement of the development of anion-exchange separation of african trypanosomes from blood led to two decades of activity when, for the first time, considerable progress was made in the intrinsic characterization of these parasites. such characterization depended on establishing high infections in laboratory rodents. however, the collection of samples from the field was restricted by the failure of certain trypanosomes either to infect, or to multiply adequately in, rod ...19911888216
lipid peroxidation as a component in trypanocidal drug action.a representative range of trypanocides was examined for ability to induce lipid peroxidation in trypanosoma rhodesiense in vitro. because of drug interference, thiobarbituric acid (tba) chromogen production and diene conjugation u.v. absorbance assay methods were less satisfactory that glc analysis of polyenoic fatty acid loss. docosohexanoic acid (22:6) content was specifically reduced to a highly significant degree by treatment with ethidium or the lipid-soluble 4-demethoxydaunorubicin.19911888218
suppression by trypanosoma brucei rhodesiense of the capacities of human t lymphocytes to express interleukin-2 receptors and proliferate after mitogenic stimulation.we studied the suppressive effects induced in phytohemagglutinin (pha)-stimulated human peripheral blood mononuclear cells (pbmc) by purified blood forms of trypanosoma brucei rhodesiense. the parasite was found to markedly impair lymphocyte proliferation (measured in terms of [3h]thymidine incorporation). the extent of this effect increased with parasite concentration and was not due to mitogen absorption, depletion of medium nutrients, or pbmc killing by the parasite. significant reductions in ...19911894358
chemotherapy of cns-trypanosomiasis: the combined use of the arsenicals and nitro-compounds.in trypanosomiasis chemotherapy the main mode of action of the nitro-compounds, including the 5-nitroimidazoles or nitrofurans (nifurtimox) is to increase the oxidative stress on the organism either directly by the production of peroxides or indirectly by "futile redox cycling". if this is the case, then these nitro-compounds and the arsenicals should act in combination on the trypanothione oxidation-reduction reaction of the trypanosome. in this paper this has been demonstrated to occur with al ...19911896771
efficacy of combination of dfmo and diminazene aceturate in the treatment of late stage trypanosoma brucei brucei infection in rats.the therapeutic activity of difluoromethylornithine and diminazene aceturate alone and in combination was investigated in albino rats with late stage trypanosoma brucei brucei infection. the criteria used in the assessment of the trypanocidal effect of the compounds include the degree of parasitaemia, and frequency of relapse and death. dfmo (4 percent administered in drinking water for 6 days) and diminazene aceturate (10 mg per kg intraperitoneal) produced an intermittent aparasitaemia with re ...19911896772
therapeutic effect of berenil and samorin in mice infected with four trypanosome populations isolated from zambian cattle.four populations of trypanosoma congolense and trypanosoma brucei brucei were isolated from cattle under different management practices and environments in zambia. all four isolates had varied responses to both diminazene aceturate (berenil) and isometamidium chloride (samorin) as curative drugs in infected mice. trypanosomes from a traditionally managed herd in a high-tsetse-challenge area had the strains most resistant to berenil, with maximum curative dose of 45 mg kg-1 body weight. another i ...19911897118
trypanosoma brucei: cytotoxicity of host high-density lipoprotein is not mediated by apolipoprotein a-i. 19911901271
alterations in krebs cycle enzyme activities and carbohydrate catabolism in two strains of trypanosoma brucei during in vitro differentiation of their bloodstream to procyclic stages.a rapid switch from a fermentative to a primarily oxidative type of glucose utilization was observed during in vitro differentiation of trypanosoma brucei stib348 and eatro1244 bloodstream to procyclic trypomastigotes. in accordance with previously published reports bloodstream populations produced pyruvate as the major end product of glucose catabolism, together with very small amounts of co2, succinate and glycerol. during differentiation pyruvate excretion decreased within 48 h to the low lev ...19911904988
rna polymerase i can mediate expression of cat and neo protein-coding genes in trypanosoma brucei.we show that the ribosomal rna (rrna) promoter can efficiently direct expression of protein-coding genes in the parasitic protozoan trypanosoma brucei. the rrna promoter was characterized by: (i) point mutations at the rrna transcription initiation site which completely abolished its promoter function in transient cat transformation assays; (ii) the alpha-amanitin resistance of transcription of rrna promoter-neomycin phosphotransferase (neo) genes in stably transformed trypanosomes; and (iii) th ...19911915299
bidirectional activating signals between trypanosoma brucei and cd8+ t cells: a trypanosome-released factor triggers interferon-gamma production that stimulates parasite growth.the hemoflagellate trypanosoma brucei (t.b.) is the cause of african sleeping sickness. t. b. brucei which is pathogenic for rodents but nonpathogenic for humans was used to examine the interactions between the parasite and mononuclear cells (mnc). co-cultivation in vitro of rat or human mnc and t.b. brucei resulted in a rapid non-antigen-specific release of interferon-gamma (ifn-gamma) which was dependent on cd8+ lymphoid cells. the parasites triggered mnc proliferation if ifn-gamma was blocked ...19911915554
the mevalonate pathway in the bloodstream form of trypanosoma brucei. identification of dolichols containing 11 and 12 isoprene residues.the major surface antigen of the bloodstream form of trypanosoma brucei, the variant surface glycoprotein, is attached to the plasma membrane via a glycosylphosphatidylinositol anchor. the biosynthesis of the glycosylphosphatidylinositol anchor, as well as the assembly of the asparagine-linked oligosaccharide chains found on the variant surface glycoproteins, involves polyisoprenoid lipids that act as sugar carriers. preliminary observations (menon, a.k., schwarz, r.t., mayor, and cross, g.a.m. ...19911918042
an mrna-dependent in vitro translation system from trypanosoma brucei.we have demonstrated efficient protein synthesis in a cell-free system from the bloodstream form of trypanosoma brucei. this system was able to translate endogenous mrna, added mrna, or (apparently at much lower efficiency) three synthetic rna transcripts lacking 5' mini-exon and 3' poly(a) sequences. translation was resistant to chloramphenicol and greater than 95% inhibited by low concentrations of anisomycin and puromycin, but only partially inhibited by cycloheximide. variant surface glycopr ...19911922198
alpha-amanitin-resistant transcription units in trypanosomes: a comparison of promoter sequences for a vsg gene expression site and for the ribosomal rna genes.transcription of the predominant surface antigen genes in trypanosoma brucei is unusual in its resistance to the rna polymerase inhibitor alpha-amanitin, a property typical for rdna transcription in eukaryotes. transcription of most other protein-coding genes in trypanosomes is sensitive to alpha-amanitin. to investigate whether rna polymerase i, the polymerase that transcribes rrna genes, can give rise to functional mrnas in trypanosomes, we have fused the putative promoter of the t.brucei rrna ...19911923801
5'-alkyl-substituted analogs of 5'-methylthioadenosine as trypanocides.5'-deoxy-5'-(methylthio)adenosine (mta) is a by-product of polyamine metabolism and is phosphoryolytically cleaved to adenine and 5-deoxy-5-(methylthio)ribose-1-phosphate (mtr-1-p) by mta phosphorylase. in eukaryotes, adenine is subsequently salvaged and converted to nucleotides, while mtr-1-p is converted to methionine. we examined 5'-deoxy-5'-substituted analogs of mta for trypanocidal activity in vitro and in vivo. 5'-deoxy-5'-(hydroxyethyl)thioadenosine (heta) and its 5'-bromo,5'-chloro and ...19911929287
trypanosoma brucei glycosomal glyceraldehyde-3-phosphate dehydrogenase genes are stage-regulated at the transcriptional level.regions 5' of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (ggapdh) gene from trypanosoma brucei were tested for their ability to promote chloramphenicol acetyl-transferase (cat) expression on reintroduction by electroporation into the parasite. deletion analysis mapped the ggapdh promoter to within 403 nts of the start of translation. a transcription initiation site was mapped at around -190 nts from the atg start codon by rnase protection and by primer extension. the higher expressi ...19911935905
specificity of glucose transport in trypanosoma brucei. effective inhibition by phloretin and cytochalasin b.glucose transport in the bloodstream form of the protozoan parasite trypanosoma brucei was characterized by enzymatically measuring the d-glucose uptake. uptake kinetics showed a concentration-dependent saturable process, typical for a carrier-mediated transport system, with an apparent km = 0.49 +/- 0.14 mm and vmax = 252 +/- 43 nmol.min-1.mg cell protein-1 (equal to 2.25 x 10(8) trypanosomes). the specificity of glucose transport was investigated by inhibitor studies. glucose uptake was shown ...19911935976
homologous recombination in the tandem calmodulin genes of trypanosoma brucei yields multiple products: compensation for deleterious deletions by gene amplification.homologous recombination between a calmodulin-neomycin-resistance fusion gene and the trypanosoma brucei chromosome takes place not only in the large 5'- and 3'-flanking segments of the calmodulin locus but also in any of the four tandem genomic calmodulin genes. this results in a recombined locus consisting of the chimeric neor gene and four, three, two, one, or zero functional calmodulin genes. cells bearing this latter event have half of their normal number of intact calmodulin genes and an a ...19911936992
variant specific glycoprotein of trypanosoma brucei consists of two domains each having an independently conserved pattern of cysteine residues.the complete amino acid sequences for nine variant specific glycoproteins (vsgs) of trypanosoma brucei are presented. these have more than doubled the size of the vsg sequence data base and have enabled a new and more rigorous comparison to be made between amino acid sequences of different vsgs. each vsg can be defined as a combination of an n-terminal domain type and a c-terminal domain type, based on the distribution of cysteine residues within the molecule. this identifies three n-terminal do ...19911942032
the actin gene promoter of trypanosoma brucei.the actin genes of trypanosoma brucei are transcribed constitutively during the parasite life-cycle, by a polymerase sensitive to alpha-amanitin. the start region of the actin gene transcription unit was mapped by virtue of the accumulation of promoter-proximal transcripts which occurs following moderate uv irradiation. this region, located about 4 kilobases upstream from the genes, was able to direct transient expression of the bacterial chloramphenicol acetyl transferase (cat) gene in both blo ...19911945875
growing and in-situ processing of cells on beem capsule caps for scanning electron microscopy.a simple technique for processing cells grown on beem capsule caps for scanning electron microscopic (sem) observation is described. the cells adhere to a substratum on the inner surface of caps coated with either an egg white-polyvinylpyrrolidone solution or a polylysine solution in the case of eukaryotic cells and an agar solution in the case of bacteria. the adhering cells are cultured and then processed in situ for sem observation. electron micrographs revealed details of the shape of the ce ...19911947942
intermolecular interactions involved in the association of the variant surface glycoprotein of trypanosoma brucei.trypanosomes in their mammalian host are covered by the densely packed variant surface glycoprotein (vsg). depending on the presence or absence of a glycosyl-phosphatidyl inositol anchor. vsg is accessible as soluble globular protein (svsg), or as insoluble membrane form (mfvsg). in order to get insight into the two-dimensional association of vsg within the surface layer, protein-protein interactions were investigated in a wide range of protein concentrations. no self-assembly of svsg could be d ...19911958317
genetics of antigenic variation in african trypanosomes.the major surface antigens of trypanosoma brucei are the vsg (variant surface glycoprotein) at the bloodstream stage, and procyclin at the procyclic stage. variation in the vsg allows the parasite to escape the antibody response of its mammalian host. this occurs through either dna rearrangement in the telomeric vsg gene expression site, or alternate activation, without dna rearrangement, of different telomeric expression sites. the vsg and procyclin genes each belong to large, polycistronic tra ...19911961983
glucose uptake by trypanosoma brucei. rate-limiting steps in glycolysis and regulation of the glycolytic flux.glucose uptake and metabolism in the bloodstream form of the glycosome-containing protozoan parasite trypanosoma brucei was measured using 14c-labeled glucose in combination with the silicone oil centrifugation technique in short term (5-60 s) incubations. glucose rather than glucose analogues was used to study the interrelation between the uptake process and the subsequent metabolic steps. glucose uptake over the plasma membrane occurred by facilitated diffusion, which limited the overall glyco ...19911985967
transient activity assays of the trypanosoma brucei variant surface glycoprotein gene promoter: control of gene expression at the posttranscriptional level.the putative promoter of the variant surface glycoprotein (vsg) gene of trypanosoma brucei was cloned into a plasmid containing the chloramphenicol acetyltransferase (cat) gene. after electroporation into trypanosomes, this construct directed the expression of the cat reporter gene. the essential region for promoter activity was found to reside within 88 bp upstream of the putative transcription start site. transcription of the cat construct occurred at approximately the same level in both blood ...19911986230
endopeptidase variations among different life-cycle stages of african trypanosomes.lysates of different life-cycle stages of trypanosoma congolense, trypanosoma vivax and trypanosoma brucei were analysed for endopeptidase activity, using reaction conditions which permitted a distinction to be made between lysosomal and non-lysosomal activity [lonsdale-eccles, j. d. & grab, d. j. (1987) eur. j. biochem. 169, 467-475]. hydrolysis of z-arg-arg-nhmec (z = benzyloxycarbonyl, nhmec = 7-amino-4-methylcoumaryl) and z-gly-gly-arg-nhmec occurred predominantly at alkaline ph and was obse ...19911991468
a new photometric assay for testing trypanocidal activity in vitro.a new in vitro test was developed to assess the trypanocidal activity of compounds against axenically grown trypanosoma brucei bloodstream forms. trypanosomes from continuous culture were exposed to series of drug dilutions in a microtiter plate. after an incubation time of 72 h at 37 degrees c, the ph indicator of the medium had changed its colour in non-inhibited cultures due to the production of pyruvate. inhibited cultures showed less, if any, colour changes. plates could be read by eye or u ...19911994369
effect of polyclonal anti-procyclic antibodies on development of trypanosoma brucei brucei in tsetse flies.results obtained in experiments testing the efficacy of anti-procyclic-form rabbit sera on the development of homologous and heterologous stocks of trypanosoma brucei brucei in glossina morsitans morsitans indicated that this development was affected little, or not at all, by such sera. the absence of effect of anti-procyclic stage antibodies can be explained by the failure to detect by either direct or indirect fluorescent antibody methods the presence of antibodies acquired in vivo by either t ...19911994370
a similar gene is shared by both the variant surface glycoprotein and procyclin gene transcription units of trypanosoma brucei.the genes for the variant surface glycoprotein (vsg) and procyclin are expressed in a mutually exclusive manner during the life cycle of trypanosoma brucei and synthesize the most abundant mrnas specific to the bloodstream and procyclic stages of the parasite, respectively. genes belonging to the polycistronic transcription unit of the vsg gene (expression site-associated genes [esags]) are uniquely expressed in the bloodstream form, but some members of esag families (genes related to esags [gre ...19911996104
expression and deletion analysis of the trypanosoma brucei rhodesiense cysteine protease in escherichia coli.trypanosoma brucei, the cause of african sleeping sickness, differentiates in the mammalian bloodstream from a long, slender trypanosome into a short, stumpy trypanosome. this event is necessary for infection of the tsetse fly and maintenance of the life cycle. we have previously shown that the stumpy form contains 10- to 15-fold-greater cysteine protease activity than either the slender form or the insect midgut procyclic, and we have isolated a cdna encoding the protease. in order to determine ...19911997411
a novel suicide inhibitor strategy for antiparasitic drug development.dl-alpha-difluoromethylornithine (dfmo), a suicide inhibitor of eukaryotic ornithine decarboxylase (odc), has therapeutic activities against african trypanosomiasis. the ki value of dfmo for odc of trypanosoma brucei is somewhat higher than that for mouse odc. the therapeutic efficacy of dfmo cannot therefore be attributed to a preferential inhibition of the parasite enzyme. the t. brucei gene encoding odc was cloned and sequenced, and the derived amino acid sequence has 61.5% homology with that ...19912005184
stable integrative transformation of trypanosoma brucei that occurs exclusively by homologous recombination.a calmodulin-neomycin-resistance fusion gene was introduced into trypanosoma brucei by electroporation, and stably transformed cell lines were obtained. in all of the transformants, the fusion gene had integrated into the host genome at the cognate locus, evidently by homologous recombination within flanking calmodulin dna. this unusual observation distinguishes trypanosomes as the only eukaryote other than yeast known to undergo gene targeting in essentially 100% of the stable transformants. it ...19912006150
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