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molecular identity and location of invariant antigens on trypanosoma brucei rhodesiense defined with monoclonal antibodies reactive with sera from trypanosomiasis patients.monoclonal antibodies (mabs) which are reactive with several antigenically distinct variable antigen types were prepared by immunization with trypanosoma brucei rhodesiense. certain mabs were shown to be specific for members of the genus trypanosoma and not reactive with leishmania spp. or plasmodium falciparum by the indirect immunofluorescence assay. these genus-specific mabs were used to identify the molecular location of these invariant antigen determinants in whole t. brucei rhodesiense ant ...19853905617
independent expression of the metacyclic and bloodstream variable antigen repertoires of trypanosoma brucei rhodesiense.the variable antigen repertoire expressed by metacyclic trypanosoma brucei rhodesiense is not influenced by the anamnestic expression whereby the variable antigen type (vat) ingested by a tsetse fly is present at high levels in early bloodstream populations of fly-infected mice. this has been demonstrated by feeding to glossina morsitans a trypanosome line expressing a vat which is normally a component of the metacyclic repertoire. the vat did not constitute a significantly increased proportion ...19863960594
trypanosoma brucei rhodesiense: enhancement of infection rates in the tsetse fly, glossina morsitans, by feeding artificial bloodmeal mixtures.low mature salivary gland (sg) infection rates (6%) in less than 24-hour-old flies fed on blood containing bloodform trypanosomes can be significantly enhanced by feeding flies an artificial mixture containing procyclic forms in a red cell: culture medium mixture (procyclic mixture, sg rate = 21.0%). however, enhancement is not solely a function of the use of procyclic forms since blood forms fed to flies in the same red cell: culture medium mixture produce sg rates (15.4%) intermediate to those ...19853970311
inosine analogs as chemotherapeutic agents for african trypanosomes: metabolism in trypanosomes and efficacy in tissue culture.certain purine analogs, the pyrazolopyrimidines, are effective chemotherapeutic agents against leishmania spp. and trypanosoma cruzi both in vitro and in some clinical models. heretofore they have not been effective against the african trypanosomes; this suggested that these organisms were not comparable to the other pathogens with respect to their purine metabolism. we have studied the efficacy and metabolism of the pyrazolopyrimidine bases allopurinol and thiopurinol, their respective ribonucl ...19853985595
characterization of the trypanosoma brucei 5s ribosomal rna gene and transcript: the 5s rrna is a spliced-leader-independent species.recent studies have shown that transcription occurs discontinuously for many genes in trypanosoma brucei. to further investigate details of transcription in trypanosomes, the genes for the 5s ribosomal rna from trypanosoma brucei rhodesiense and trypanosoma brucei brucei were cloned. sequence analysis and southern blotting showed the genes to be arranged in highly conserved tandem repeats of approx. 740 bp, which have no relation to the conserved 35-base spliced-leader repeat element. the genes ...19854029619
tubulin genes of the african trypanosome trypanosoma brucei rhodesiense:nucleotide sequence of a 3.7-kb fragment containing genes for alpha and beta tubulins.most tubulin genes of the african trypanosome trypanosoma rhodesiense are contained in 3.7-kb tandemly repeating units. one member of the 3.7-kb repeat family has been isolated from a t. rhodesiense genomic library, cloned, and sequenced. the 3646-bp fragment contains a complete alpha-tubulin gene and portions of two beta-tubulin genes. no introns are present. the genes are separated by 634- and 333-bp intergenic regions, which lack typical eukaryotic promoter and poly(a) signal sequences. howev ...19854043732
characterization of potentially man-infective trypanosoma brucei from an endemic area of sleeping sickness in kenya.human trypanosomiasis caused by trypanosoma brucei rhodesiense has affected the human population in lambwe valley, western kenya, for more than 20 years. a characteristic feature of the disease has been the repeated recrudescense at restricted residual foci. studies carried out on the incidence of trypanosome infection rates in the vector glossina pallidipes during the last two years have shown high incidence of pathogenic african trypanosomes in the area. an overall trypanosome infection rate o ...19854081544
immunopathological aspects of trypanosomal meningoencephalitis in vervet monkeys after relapse following berenil treatment.four quarantined vervet monkeys were treated with intramuscular berenil in patent cns infection after experimental trypanosome inoculation with trypanosoma brucei rhodesiense or t. brucei brucei. all four animals relapsed in the post-therapeutic survival time of 37 to 209 days when they had fully developed meningoencephalitis in histological sections with the presence of interstitial intracerebral trypanosomes, which were confirmed in two monkeys by electron microscopy. in both, sequential sampl ...19854082265
antigenicity and stilbamidine resistance in trypanosoma brucei rhodesiense. 19734204739
the effect of immune inhibition on pleomorphism in trypanosoma brucei rhodesiense. 19744607181
isolation, partial purification, and properties of thymidine kinase from trypanosoma (trypanozoon) brucei rhodesiense. 19725022867
experimental infections of the chimpanzee (pan troglodytes) with trypanosoma brucei brucei and trypanosoma brucei rhodesiense. 19715145112
lesions in the central nervous system of a chimpanzee infected with trypanosoma brucei rhodesiense. 19705442035
african trypanosomes contain calmodulin which is distinct from host calmodulin.studies were initiated to determine whether african trypanosomes utilize ca2+ fluxes to coordinate complex morphological and biochemical life cycle changes. we have identified the ubiquitous intracellular ca2+ receptor, calmodulin, in two developmental stages of trypanosoma brucei rhodesiense. the transition from rapidly dividing, slender bloodstream trypomastigotes to slow growing procyclics in axenic culture was accompanied by changes in specific calmodulin content (3 micrograms/mg cell protei ...19836135450
further studies on difluoromethylornithine in african trypanosomes.dl-alpha-difluoromethylornithine (dfmo), a specific enzyme-activated irreversible inhibitor of ornithine decarboxylase (odc) was previously shown to cure mice infected with trypanosoma brucei brucei, a parasite of game and cattle in africa and trypanosoma brucei rhodesiense, a human african sleeping sickness pathogen. our studies now indicate that dfmo blocks ornithine decarboxylase and lowers trypanosome polyamine levels in vivo. polyamine uptake in t.b. brucei also resembles that previously de ...19816175860
topologic mapping of protective and nonprotective epitopes on the variant surface glycoprotein of the wratat 1 clone of trypanosoma brucei rhodesiense.monoclonal antibodies were used in competitive antibody binding assays to define and map epitopes on the variant surface glycoprotein of the wratat 1 clone of t. b. rhodesiense. by using a panel of 30 wratat 1-specific monoclonal antibodies, 16 epitopes were defined that fall into four clusters, having 1, 1, 3, and 11 distinct epitopes respectively. all epitopes were easily classified as being 1) exposed uniformly on the surface of the trypanosome, 2) exposed only in the region of the flagellar ...19846199421
the public health importance of african trypanosomiasis in north east zambia.a survey for sleeping sickness (trypanosoma brucei rhodesiense) in villages in the northern luangwa valley found a point prevalence of parasitaemia of 5.8 per thousand; the incidence of the disease was estimated at about 1% per annum. none of the cases found had sought treatment and pre-symptomatic cases may represent an important reservoir of infection to others. other frequent parasitemias in the population included malaria (p. falciparum, p. malariae and p. ovale) which is hyperendemic and di ...19846335610
experimental chronic trypanosoma brucei rhodesiense infection in microtus montanus.adult microtus montanus were inoculated with a recently isolated strain of trypanosoma brucei rhodesiense of human origin. the animals developed subacute to chronic infection and low-grade parasitemia. histopathological examination of the heart revealed a severe pancarditis resulting in pronounced weight loss, and survival times of 5-8 weeks, preventing development of meningoencephalitis. in the brain a moderate meningitis was found, usually associated with moderate numbers of parasites in the c ...19836353961
immunoconglutinin and suppression of an induced immune response by plasma from rats infected with trypanosoma brucei rhodesiense.fresh plasma from rats infected with trypanosoma brucei rhodesiense, incubated with splenic lymphocytes from rats previously immunized with sheep blood cells, suppressed the capacity of the splenic lymphocytes to produce antibody as was indicated by reductions in the numbers of hemolytic jerne plaques produced by the treated cells. the effect was maximal in plasma samples drawn on the sixth to eighth day of infection when they contained elevated amounts of soluble immune complex, high titers of ...19846376751
genetics of resistance to the african trypanosomes. iv. resistance of radiation chimeras to trypanosoma rhodesiense infection.the cellular bases of resistance to the african trypanosomes were examined in inbred mice. as part of these studies, reciprocal bone marrow cell transplants were performed between h-2 compatible mice which differ in relative resistance to trypanosoma brucei rhodesiense infection. survival times, parasitemias and igm antibody responses to the surface antigen of the infecting variant type were measured in these semiallogeneic bone marrow chimeras. relatively resistant c57bl/10 mice, intermediate a ...19846378394
in vivo analysis of impaired macrophage bactericidal capacity during experimental african trypanosomiasis.since innate resistance of mice to salmonella typhimurium depends on an intact macrophage system, we have used this bacterium to investigate the effect of trypanosoma brucei subsp. rhodesiense infection on macrophage phagocytic and cytolytic function. cba/caj mice infected with t. brucei subsp. rhodesiense have decreased resistance to s. typhimurium, since doubly infected mice rapidly succumb to sublethal doses of s. typhimurium. although trypanosomiasis is known to suppress antibody formation, ...19846389356
variable antigen type (vat) composition of trypanosoma brucei rhodesiense: discrepancy between results obtained using vat-specific monoclonal antibodies and rabbit antisera.monoclonal antibodies have been made against clones of trypanosoma brucei rhodesiense from the wratar 1 serodeme and analyzed by indirect immunofluorescence assay for specificity against homologous and heterologous clones. these antibodies were shown to be variable antigen type (vat)-specific as they identified the majority of parasites in the homologous clones but few parasites in other clones. the reactivities of these vat-specific monoclonal antibodies with uncloned human trypanosome isolates ...19846391220
complement reversal of immunosuppression induced with plasma of rats infected with trypanosoma brucei rhodesiense.suppression of antibody production by splenic lymphocytes from rats immunized with sheep red blood cells (srbc) after incubation with plasma from rats infected with trypanosoma brucei rhodesiense was confirmed. suppressive activity became evident in plasma after the sixth day of infection and was manifested by reduction in the number of hemolytic jerne plaques produced by the treated cells. the activity was temporally associated with increased amounts of soluble immune complex (sic) reduced tite ...19846396393
nonvariant antigens limited to bloodstream forms of trypanosoma brucei brucei and trypanosoma brucei rhodesiense.the presence of nonvariant antigens (nvas) limited to bloodstream forms of trypanosoma brucei brucei and trypanosoma brucei rhodesiense was demonstrated for the first time by immunodiffusion and immunoelectrophoresis. noncloned and cloned populations were employed in preparation of polyclonal antisera in rabbits and of antigens to be used in the immunologic reactions. the nvas could be shown best in systems in which hyperimmune rabbit sera (adsorbed with procyclic forms to eliminate antibodies a ...19846439856
morphological changes in trypanosoma brucei rhodesiense following inhibition of polyamine biosynthesis in vivo.the effect of alpha-difluoromethylornithine (dfmo) treatment on the morphology of african trypanosomes was investigated. for this purpose inbred mice were immunosuppressed and infected with a clone of the protozoan blood parasite trypanosoma brucei rhodesiense. the mice were then treated with dfmo, an irreversible inhibitor of ornithine decarboxylase, which inhibits polyamine synthesis. dfmo treatment in the absence of host immunity resulted in arrest of cytokinesis of the trypanosomes and many ...19846440309
the experimental use of 'sentinel' goats to monitor trypanosomiasis in a zambian sleeping sickness focus. part i. the isolation of trypanosoma brucei rhodesiense-like organisms from a 'sentinel' domestic goat. 19846476933
the experimental use of 'sentinel' goats to monitor trypanosomiasis in a zambian sleeping sickness focus. part ii. the short duration and spontaneous remission of a trypanosoma brucei rhodesiense-like infection in a naturally infected 'sentinel' goat. 19846476934
a longitudinal study of the susceptibility to normal human serum of a trypanosoma brucei rhodesiense clone non-cyclically passaged in rats. 19846535712
characterization of the genes specifying two metacyclic variable antigen types in trypanosoma brucei rhodesiense.bloodstream trypanosomes evade the immune system of their mammalian host by sequentially expressing a large number of different variable surface glycoproteins (vsgs). in contrast, metacyclic trypanosomes, the final developmental stage in the tsetse fly, express a much more restricted set of vsgs. these metacyclic vsgs are the first to be exposed to the immune system of the mammalian host after infection and may offer the potential for the eventual development of a vaccine. we have identified cdn ...19846593722
trypanosomal surface coat variant antigen causes polyclonal lymphocyte activation.variant antigen, the primary component of the surface coat of the salivarian trypanosome, when injected i.v. into mice at dosages encountered during acute infections, produced some of the immunopathogenic phenomena associated with acute african trypanosomiasis. trypanosome-infected and variant antigen-treated mice had splenomegaly caused by proliferation of null cells, b and t lymphocytes, and macrophages. splenic b lymphocytes were nonspecifically activated to produce antibodies to sheep erythr ...19836604754
trypanosoma brucei rhodesiense: mechanical transmission by tsetse, glossina morsitans (diptera: glossinidae), in the laboratory. 19836644759
instability of the trypanosoma brucei rhodesiense metacyclic variable antigen repertoire.trypanosoma brucei rhodesiense undergoes antigenic variation in its mammalian host by changing the glycoprotein composing its surface coat. trypanosome clones which have the same repertoire of variable antigen types (vats) are said to belong to the same serodeme. tsetse flies infected with a particular serodeme extrude infective metacyclic trypanosomes which express only a restricted part of this repertoire. as the only known acquired immunity in african trypanosomiasis is vat-specific this limi ...19836656871
african trypanosomiasis in an american hunter in east africa.an american citizen acquired african trypanosomiasis while on a hunting safari in sudan, east africa. his travel history and rapid onset of symptoms, including fever, chills, headache, lethargy, and weight loss, were suggestive of trypanosoma brucei rhodesiense infection, and trypanosomes were demonstrated in routine blood smears and buffy-coat preparations. despite the presence of headaches, nuchal rigidity, and csf pleocytosis, he was treated for non-cns african trypanosomiasis, based on a nor ...19836679214
the effects of different eland and waterbuck sera on trypanosoma brucei rhodesiense clones from lion and from man. 19826764401
cryptic stage of sleeping-sickness trypanosome developing in choroid plexus epithelial cells.electronmicrographs of the choroid plexus from rats infected with trypanosoma brucei rhodesiense showed that trypomastigotes from the perivascular spaces may penetrate and undergo multiple division in the ependymal cells which locally constitute the blood-brain barrier. progressive degeneration of the ependymal cell liberates trypomastigotes back into the perivascular space, from which re-entry into the blood may occur. re-entry to the blood does not take place from any tissues other than the br ...19826814567
purine metabolism in the bloodstream forms of trypanosoma gambiense and trypanosoma rhodesiense.bloodstream forms of trypanosoma brucei gambiense and trypanosoma brucei rhodesiense are incapable of de novo purine synthesis. purine bases are converted directly to ribonucleotides and with the exception of guanine, are stable. guanine is incorporated directly into ribonucleotides and also deaminated to xanthine. purine ribonucleosides are hydrolyzed rapidly; these reactions may limit their incorporation since purine bases label the nucleotide pools more efficiently than do ribonucleosides. th ...19826817814
phagocytosis of trypanosoma brucei rhodesiense by peritoneal macrophages: a study by scanning electronmicroscopy.phagocytosis of trypanosoma brucei rhodesiense by peritoneal macrophages takes place by seizure of the trypomastigote by either end but usually by the anterior. a lamellar sheath similar to that seen in phagocytosis of the promastigote of leishmania is observed, but it is smaller and does not proceed to envelop the living parasite. the attached trypomastigote becomes pitted and appears to have been killed and partially destroyed before it is completely engulfed.19836842569
african sleeping sickness: new evidence that mature tsetse flies (glossina morsitans) can become potent vectors.starved mature male tsetse flies (21 to 25 days old) are capable of developing salivary gland (sg) infections of trypanosoma brucei rhodesiense at rates nearly comparable to teneral males less than 24 hours old when given an infective meal containing parasites, horse red cells and culture medium. although the over-all sg infection rate for mature males starved for three, four or five days before infection was about half that for teneral males less than 48 hours old (8.0% v. 15.6%), males starved ...19826926764
effects of some african game animal sera on trypanosoma brucei rhodesiense and t.b. brucei clones.the effects of different african game sera on trypanosoma brucei rhodesiense and t.b. brucei clones have been studied in vitro and in vivo, for the first time, using a modified version of the blood incubation infectivity test (biit). trypanosomes were incubated in vitro with serum samples from a number of different game animal species and their subsequent infectivity for proven susceptible rats then examined after one hour and 8 hours of serum incubation. sera from eland, waterbuck and, to a les ...19827051497
comparative analysis of procedures used to isolate variant antigen from trypanosoma brucei rhodesiense.comparisons made among various procedures leading to the isolation of variant antigen from trypanosoma brucei rhodesiense bloodstream trypomastigotes. as a means of parasite disruption, freeze-thawing solubilized 36% more variant antigen than did sonication. protease inhibitors were important additions to the suspension prior to cellular disruption. if trypanosomal extracts were frozen for at least 1 wk prior to chromatographic isolation of variant antigen, recovery of the antigen was reduced by ...19827119984
trypanosoma brucei rhodesiense (trypanosomatidae): factors influencing infection rates of a recent human isolate in the tsetse glossina morsitans (diptera: glossinidae). 19827120305
trypanosoma brucei rhodesiense infection in vervet monkeys. i. parasitologic, hematologic, immunologic and histologic results.twenty vervet monkeys infected with t. rhodesiense (eatro 1989) developed chronic disease with an average duration of 65 days (variation 35-107 days). with respect to the course of the disease, and to the hematologic, immunologic and histological findings, the disease faithfully mirrored human t. rhodesiense infection. in all animals, parasitization of the csf occurred only a few weeks after infection, and was accompanied by an increase in the cell count and the appearance of igm in the csf. the ...19827164166
trypanosoma brucei rhodesiense infection in vervet monkeys. ii. provocation of the encephalitic late phase by treatment of infected monkeys.four out of 8 monkeys infected with trypanosoma rhodesiense and treated with trypanocidal drugs at various intervals after infection (days 55-58, days 62-65, day 68) developed encephalitis. in 2 of these animals, killed 2 weeks after treatment, the encephalitis presenting was incipient; the other 2 monkeys died as a result of severe encephalitis a little more than 2 and 3 months after treatment, respectively. at the time of treatment, the animals revealed a parasitization of the csf, but there w ...19827164167
some phenomena associated with the development of trypanosoma brucei rhodesiense infections in the tsetse fly, glossina morsitans.immature salivary gland (sg) infections averaging 10(3) parasites per fly can apparently develop into mature gland infections averaging 10(5) parasites per fly in as little as 4 days. frequently flies which extrude parasites in their saliva prove to have no parasites in the sg, but often show trypanosomes in the esophagus, cibarial pump, and proboscis. in some instances, sg infections have cleared, resulting in a loss of infectivity. results of studying numbers of parasites regurgitated upon fee ...19817258478
immunologic reactions associated with anemia, thrombocytopenia, and coagulopathy in experimental african trypanosomiasis.rats infected with trypanosoma brucei rhodesiense developed anemia, thrombocytopenia, and hypocomplementemia. anemia, thrombocytopenia, and sharp reductions in parasitemia were associated with elevated titers of cold-active hemagglutinin, antibody to fibrinogen/fibrin-related products, and immunoconglutinin. depletion of lytic complement, prolonged partial thromboplastin times, and presence of fibrin monomers in the blood occurred at the time anemia and significant elevations in precipitable imm ...19807365636
a study of the effects of some game animal tranquillising drugs on trypanosoma brucei rhodesiense infections in white rats. 19807398548
preliminary observations on the infectivity of slender forms of trypanosoma brucei rhodesiense to glossina morsitans morsitans. 19807434409
[african sleeping sickness in the netherlands].of the four most dangerous protozoal infections acquired in (sub)tropical regions, falciparum malaria, amoebic abscess of the liver, visceral leishmaniasis (kala azar) and african trypanosomiasis (sleeping sickness) only the fourth was up to now unreported in the dutch medical literature. two case histories are presented: a cameroonian woman, resident in the netherlands for two years, suffering from west african type sleeping sickness, and a dutch tourist who acquired east african trypanosomiasi ...19957477570
identification of haptoglobin as a natural inhibitor of trypanocidal activity in human serum.trypanosomes are protozoan parasites of medical and veterinary importance. trypanosoma brucei rhodesiense and trypanosoma brucei gambiense infect humans, causing african sleeping sickness. however, trypanosoma brucei brucei can only infect animals, causing the disease nagana in cattle. man is protected from this subspecies of trypanosomes by a toxic subtype of high density lipoproteins (hdls) called the trypanosome lytic factor (tlf). the toxic molecule in tlf is believed to be the haptoglobin-r ...19957479764
[horizon 2000: what are the perspectives for african trypanosomiasis?]. 19947496188
identification of trypanosomes in animals, humans and glossina.a number of biochemical methods are now available for the identification of african trypanosomes. the method of choice depends on the number of trypanosomes present in the sample and the taxonomic level required. dna probes based on repetitive dna elements allow identification to subgeneric (e.g. trypanozoon), species (e.g. trypanosoma congolense, t. simiae) or subspecific (e.g. t. congolense savannah) levels. these probes are particularly useful for identification of trypanosomes in the fly mid ...19947496192
[current therapy of trypanosomiasis].the authors review the available products used for human african trypanosomiasis (hat) chemotherapy: pentamidine, suramin, melarsoprol and the new compound dfmo. the administration of pentamidine at the beginning of the nervous stage, when the number of cells in the cerebrospinal fluid do not exceed 20/mn3 is a new approach for hat treatment. at this time of the disease, patients generally are healthy and the pentamidine therapy avoids the use of the toxic melarsoprol (arsobal). an alternative p ...19947496197
[the sleep-wake cycle during trypanosoma brucei rhodesiense human african trypanosomiasis in 2 french parachutists].polysomnography was performed in two military personnel who contracted human african trypanosomiasis (hat) in rwanda. they were evacuated to france and gramined during the fourth, sixth and eleventh months of evolution. patient a presented a meningoencephalitis with trypanosoma brucei rhodesiense (t. b. r.) in the cerebrospinal fluid. between the second and third treatments with melarsoprol, the patient presented an acute encephalitic attack with pyramidal and cerebellar symptoms, which were imp ...19947496202
trypanozoon: infectivity to humans is linked to reduced transmissibility in tsetse. i. comparison of human serum-resistant and human serum-sensitive field isolates.the transmissibility of recent isolates of human serum-sensitive (hss) and human serum-resistant (hsr) trypanozoon was compared by transmission of 37 stocks through an inbred line of glossina m. morsitans. as in previous studies maturation was found to be dependent on fly sex with males producing significantly greater proportions of salivary gland infections than females. hss stocks were, however, 1.8 times more likely to mature to mammalian infective form than hsr stocks in male tsetse and 2.7 ...19957498437
cytoskeleton-associated antigens from african trypanosomes are recognized by self-reactive antibodies of uninfected mice.serum from uninfected mice of different strains, as well as from germ-free animals, contains antibodies which react specifically with at least two trypanosomal proteins, i/6 and marp1. these antibody populations are highly specific for the respective proteins, are of similar affinity as hyperimmune antibodies, and consist of igm as well as igg isotypes. hyperimmune antibody raised against the cross-reacting trypanosomal protein i/6 detects a 60 kda protein in mouse 3t6 cells, which is a componen ...19937506406
crystallization and preliminary x-ray investigation of the recombinant trypanosoma brucei rhodesiense calmodulin.bipyramidal crystals of the recombinant calmodulin from trypanosoma brucei rhodesiense were obtained by vapor diffusion against 55% (v/v) 2-methyl-2,4-pentanediol in 0.05 m cacodylate buffer, ph 5.6. when few nucleation events occurred, crystals grew to 0.25 x 0.25 x 1.20 mm. the space group of the crystal is i4(1)22, with unit cell dimensions a = b = 56.88 a, c = 230.11 a, alpha = beta = gamma = 90 degrees, z = 16. the molecular mass and volume of the unit cell suggest that there is one molecul ...19957567957
trypanosoma brucei rhodesiense: variation in human serum resistance after transmission between bushbuck and domestic ruminants by glossina morsitans morsitans. 19957572432
cutaneous manifestations of african trypanosomiasis.dermatologists may evaluate patients with african trypanosomiasis. the currently available dermatologic literature does not review the cutaneous manifestations of african trypanosomiasis.19957574836
[antigenic variation and the problem of vaccines against african trypanosomes].african trypanosomes evade the immune response of their host through continuous changes of their major surface antigen, the vsg. this antigenic variation is achieved by either alternative activation of different expression sites for the vsg gene, or dna rearrangements occurring within a given site. several minor but invariant surface proteins have recently been characterized. this is especially the case for some surface receptors, which appear to be located in an invagination of the plasma membr ...19957581198
the inheritance of factors controlling resistance in mice infected with trypanosoma brucei rhodesiense.in crosses between 2 recombinant inbred strains of mice (b x h-2 and b x h-14), resistance to infection with trypanosoma brucei rhodesiense as measured by survival time is suggested to be controlled by a dominant gene(s). in prior studies using the same clone of trypanosomes, but a different set of inbred mouse strains, it was demonstrated that resistance in h-2 congenic mice was a recessive trait. this work suggests that in mouse trypanosomiasis, the number of genes involved in resistance and t ...19957623216
partial protection against natural trypanosomiasis after vaccination with a flagellar pocket antigen from trypanosoma brucei rhodesiense.cattle that were inoculated with an antigen derived from the flagellar pocket of trypanosoma brucei rhodesiense and then infected with trypanosoma congolense and trypanosoma vivax were compared with unvaccinated cattle when both groups of cattle were placed in regions of kenya endemic for tsetse flies known to harbour t. congolense and t. vivax. in one trial, 90 cattle were employed, 40 untreated controls, 30 cattle given prior treatment with samorin, and 20 inoculated with a flagellar pocket (f ...19957625108
inhibition of protein phosphatase 1 and 2a down-regulates beta-tubulin gene expression in trypanosoma rhodesiense.we studied the effect of okadaic acid, a specific inhibitor of serine/threonine protein phosphatase types 1 and 2a, on the expression of beta-tubulin and procyclin genes in trypanosoma rhodesiense. okadaic acid was found to decrease the steady-state level of beta-tubulin mrna about 5-fold in differentiating bloodstream trypanosomes and about 3-fold in established procyclic trypanosomes. no effect was observed on the expression of the procyclin gene. the down-regulation of beta-tubulin gene expre ...19957626112
a novel in vitro screening assay for trypanocidal activity using the fluorescent dye bcecf-am.a cell viability assay, using fluorescence measurements has been developed for the screening of new compounds against african trypanosomes. 2',7'-bis-(carboxyethyl)-5(6)-carboxyfluorescein-pentaacetoxymethyles ter (bcecf-am), an esterase substrate, was used in the assay as a marker for cell viability. fluorescence was quantified using an automated fluorescence scanner for multi-well plates. trypanosoma brucei rhodesiense, t. congolense, t. evansi and t. equiperdum from continuously growing cultu ...19957631128
activity and structure relationship of acridine derivatives against african trypanosomes.48 newly synthesized acridine derivatives of different classes were screened for antitrypanosomal activity. they showed a dose dependent effect on trypanosoma rhodesiense and t. brucei bloodstream forms measured by the inhibition of esterase activity in a fluorescence based in vitro assay. after analysis of the ic50 and mic values of the investigated acridines it was obvious that no new compound reached the level of the trypanocidal drugs in use (50 ng/ml). most of the derivatives had ic50 value ...19957631129
use of monoclonal antibodies for detecting t brucei brucei infection in splenectomised dogs.a monoclonal antibody against a plasma membrane antigen of trypanosoma rhodesiense was used for the detection of t brucei group-specific circulating antigen in 24 adult local dogs experimentally infected with t brucei brucei strain 8/18. ten of the dogs were splenectomised and the remainder non-splenectomised (intact). five dogs each from the splenectomised and intact groups were inoculated intravenously with trypanosomes. the infected dogs developed trypanosomiasis between days 4 and 8 after in ...19957650918
the kinetics of maturation of trypanosome infections in tsetse.estimates of the time delay between the infective bloodmeal and maturation (incubation or maturation time) for 4 trypanosome stocks (2 trypanozoon and 2 trypanosoma congolense) show that maturation time in tsetse is not a parasite species-specific constant. the mean incubation time of a trypanosoma brucei rhodesiense stock (eatro 2340 - 18 days) was not significantly different from one t. congolense stock (sikuda88 - 15.5 days) but was significantly greater than another (1/148 fly9 - 12.5 days). ...19957675533
trypanosoma brucei rhodesiense: membrane glycoproteins localized primarily in endosomes and lysosomes of bloodstream forms.bloodstream forms of trypanosoma brucei rhodesiense take up macromolecules in endocytic vesicles that form in a large coated pit called the flagellar pocket. glycoproteins that bind to ricin are concentrated in the flagellar pocket and in intracellular vesicles. we purified triton x-100-soluble ricin-binding glycoproteins by lectin affinity chromatography and immunized mice to generate hybridomas. monoclonal antibody produced by the cb1 hybridoma recognized heterodisperse trypanosome components ...19937685707
transport of a lysosomal membrane glycoprotein from the golgi to endosomes and lysosomes via the cell surface in african trypanosomes.gp57/42 is a membrane glycoprotein localized in the trans-golgi, flagellar pocket region of the cell surface, endosomes and lysosomes of bloodstream forms of trypanosoma brucei rhodesiense. pulse-chase immunoprecipitation experiments revealed that gp57/42 acquires a unique n-linked oligosaccharide recognized by the cb1 monoclonal antibody 20-30 minutes after protein synthesis, probably in the trans-golgi. we refer to gp57/42 molecules that carry the cb1 epitope as cb1-gp. pulse labeled cb1-gp co ...19947699016
a successful backcross in trypanosoma brucei.genetic exchange can take place between different strains of trypanosoma brucei ssp. when they are cotransmitted via the tsetse fly vector, but the mechanism and limits of compatibility between strains are ill-defined as yet. following the recovery of several hybrid genotypes with single drug resistance from a cross of drug resistant parental strains, we attempted a series of backcrosses and f1 crosses, selecting hybrids by double drug resistance. of 4 backcrosses, one produced hybrid progeny, t ...19957723777
the serum resistance-associated (sra) gene of trypanosoma brucei rhodesiense encodes a variant surface glycoprotein-like protein.in the trypanosoma brucei species, t. b. rhodesiense and t. b. gambiense represent the human infective host range variants, while t. b. brucei is lysed upon exposure to a cytotoxic factor in normal human serum. t. b. rhodesiense can occur in a serum-resistant and a serum-sensitive form. the resistance towards normal human serum was shown to be a labile character and to be determined by the environment in which the parasites live. we have clearly demonstrated the presence of rna transcripts uniqu ...19947739673
s-(5'-deoxy-5'-adenosyl)-1-aminoxy-4-(methylsulfonio)-2-cyclopentene (adomao): an irreversible inhibitor of s-adenosylmethionine decarboxylase with potent in vitro antitrypanosomal activity.the s-adenosylmethionine (adomet) analogue s-(5'-deoxy-5'-adenosyl)-1-aminoxy-4-(methylsulfonio)-2-cycl opentene (adomao) was synthesized in two of its four possible diastereomeric forms using a facile chemoenzymatic route. the trans-1r,4r- and trans-1s,4s-diastereomers of adomao, as well as the corresponding diastereomers of the unmethylated precursor molecule nor-adomao, were then evaluated as inhibitors of s-adenosylmethionine decarboxylase (adomet-dc) from both bacterial and human sources. a ...19957752200
multiple tropical pathology in an hiv-positive man. 19957779928
establishment of a partly dfmo-sensitive primate model of trypanosoma rhodesiense sleeping sickness. 19957785528
mechanism of lysis of trypanosoma brucei gambiense by human serum.resistance to lysis by human serum (hs) is an important parameter used to distinguish trypanosoma brucei brucei from both trypanosoma brucei rhodesiense and trypanosoma brucei gambiense. neither the exact nature of the trypanolytic factor (tlf) nor the mechanism of action by which hs lyses susceptible trypanosomes is well understood. this report tries to elucidate the role played by the variable surface glycoprotein (vsg) coat and trypanosome surface-related processes in the mechanism of hs lysi ...19947799165
human serum-sensitive trypanosoma brucei rhodesiense: a comparison with serologically identical human serum-resistant clones.trypanosoma brucei rhodesiense clones, which are susceptible to lysis by normal human serum, were isolated from 3 different human serum-resistant clones originally derived from strain etat 1.10. serologically, these pairs of serum-sensitive and serum-resistant clones displayed the same variant surface glycoprotein (vsg) on their surface. acquisition of human serum sensitivity correlated with susceptibility to lysis by human high density lipoprotein, a trypanocidal factor in normal human serum. a ...19947808471
a multiple antigen detection dipstick colloidal dye immunoassay for the field diagnosis of trypanosome infections in cattle.monoclonal antibodies (mcabs) were developed against aspartate aminotransferase purified from trypanosoma brucei rhodesiense bloodstream form (bf) soluble extracts using a combination of anion-exchange and hydrophobic interaction chromatography. mcab 1a1 was trypanozoon and nannomonas specific while 2f1 was trypanozoon bloodstream form specific. a dipstick colloidal dye immunoassay (dia) was employed as a field diagnostic test for african trypanosome infections and designed using affinity purifi ...19947886920
trypanosoma brucei rhodesiense: use of an antigen detection enzyme immunoassay for evaluation of response to chemotherapy in infected vervet monkeys (cercopithecus aethiops).thirty eight trypanosoma brucei rhodesiense-infected vervet monkeys (cercopithecus aethiops) in the late (meningoencephalitic) stage of disease, treated with various trypanocidal drugs, were monitored for a period of more than 600 days to assess the rate of clearance of trypanosome antigens from serum and cerebrospinal fluid (csf). there was a complete but gradual reduction in antigen titres, as assessed by elisa, in animals treated intravenously with melarsoprol, the standard drug for the late ...19947899795
current situation of african trypanosomiasis.african trypanosomiasis (sleeping sickness) is fatal, if untreated, and occurs in 36 african countries, south of the sahara, where some 50 million people are at risk of acquiring infection. in the absence of adequate control measures epidemics occur, which are costly and difficult to control. the history of sleeping sickness has been characterized by waves of epidemics, resurgences and outbreaks. nevertheless, sleeping sickness has been brought practically under control in the early 1950s, in we ...19937902654
isoenzyme comparison of trypanozoon isolates from two sleeping sickness areas of south-eastern uganda.the study characterized 151 trypanozoon isolates from south-east uganda by isoenzyme electrophoresis. stocks were from a range of hosts, including man, cattle, pigs, dogs and glossina fuscipes fuscipes: 104 isolates were from the busoga area, 47 were from the tororo district. stocks were characterized on thin layer starch gel using eight enzyme systems: alat, asat, icd, mdh, me, nhd, nhi, pgm. enzyme profiles were generally typical of east africa; new patterns for icd and me were detected. trypa ...19937903841
a common pyrimidine-rich motif governs trans-splicing and polyadenylation of tubulin polycistronic pre-mrna in trypanosomes.in trypanosomes, the generation of monocistronic mrnas from polycistronic precursors is achieved via rna processing, namely trans-splicing of the spliced leader sequence at the 5' end and cleavage/polyadenylation at the 3' end of the mrna coding region. recent evidence raised the intriguing possibility that these two reactions are coupled. to begin a dissection of the signals required for mrna 5'-end and 3'-end formation and to uncover potential interactions between trans-splicing and polyadenyl ...19947907303
delayed recovery of adrenocortical and testicular function after chemotherapy of human trypanosomiasis.the following indicators of pituitary, adreno-cortical and testicular function were measured in 58 male african trypanosomiasis patients from western kenya; plasma cortisol, luteinizing hormone (lh) and testosterone levels. the measurements were carried out by specific radioimmunoassay methods in early and late stage infected patients on admission to hospital and in both groups of patients after one month of chemotherapy. packed cell volume (pcv) and hemoglobin levels were also measured in all t ...19947942356
risk factors assessment for t. b. rhodesiense sleeping sickness acquisition in s.e. uganda. a case-control study.the major risk factors associated with acquisition of t. b. rhodesiense sleeping sickness in the busoga focus, s.e. uganda were investigated using a case-control study. 122 cases and 244 matched controls were used in the study. for each case two age-, sex- and resistance controls (1 matched nearest neighbour control and 1 village control) were selected. patients and controls answered the same questionnaire which had been developed and field tested before the field study started. a logistic regre ...19947944647
the persistence of genetic homogeneity among trypanosoma brucei rhodesiense isolates from patients in north-west tanzania.trypanosomes isolated during 1991 from nine patients with rhodesian sleeping sickness in north-west tanzania were genetically characterized by electrophoresis of ten enzymes. eight isolates were allocated to a known zymodeme (z306); another had an enzyme profile (z379) not previously encountered. an example of z306 has been previously isolated in 1971, nearby in a part of rwanda adjacent to the border with tanzania; in addition, a closely related isolate, in z307, was collected in 1959 from a pa ...19948023757
a monocistronic transcript for a trypanosome variant surface glycoprotein.many protein-encoding genes of african trypanosomes are transcribed as large polycistronic pre-mrnas that are processed into individual mrnas containing a 5' spliced leader and 3' poly(a). the 45- to 60-kb pre-mrnas encoding some variant surface glycoproteins (vsgs) contain as many as eight unrelated coding regions. here we identify the promoter for a metacyclic vsg gene that is expressed without duplication in a bloodstream trypanosome clone. this 70-bp promoter is located 2 kb upstream of the ...19948035832
the treatment of human african trypanosomiasis. 19948122565
immunoassay of circulating trypanosomal antigens in sleeping sickness patients undergoing treatment.sera from 99 patients infected with trypanosoma brucei rhodesiense and undergoing treatment, were analyzed for circulating trypanosomal antigens using a sandwich antigen-trapping enzyme-linked immunosorbent assay (elisa). trypanosomal antigens were detected in 83 (84%) of the patients. post-treatment antigen profile in 67 patients showed five distinct patterns: in 48% of the patients antigen levels remained elevated throughout the time of hospitalisation and follow-up; in 31%, antigens dropped t ...19948150987
midgut lectin activity and sugar specificity in teneral and fed tsetse.midgut infection rates of trypanosoma congolense in glossina palpalis palpalis and of trypanosoma brucei rhodesiense in glossina pallidipes are potentiated by the addition of d+ glucosamine to the infective feed, but not to the levels of super-infection reported for g.m.morsitans, g.p.palpalis and g.pallidipes are shown to possess two trypanocidal molecules: a glucosyl lectin which can be inhibited by d+ glucosamine and a galactosyl molecule inhibited by d+ galactose. addition of both d+ glucosa ...19948161852
evidence for an interplay between cell cycle progression and the initiation of differentiation between life cycle forms of african trypanosomes.successful transmission of the african trypanosome between the mammalian host blood-stream and the tsetse fly vector involves dramatic alterations in the parasite's morphology and biochemistry. this differentiation through to the tsetse midgut procyclic form is accompanied by re-entry into a proliferative cell cycle. using a synchronous differentiation model and a variety of markers diagnostic for progress through both differentiation and the cell cycle, we have investigated the interplay betwee ...19948195296
a strand bias occurs in point mutations associated with variant surface glycoprotein gene conversion in trypanosoma rhodesiense.we previously described a bloodstream trypansoma rhodesiense clone, mvat5-rx2, whose isolation was based on its cross-reactivity with a monoclonal antibody (mab) directed against a metacyclic variant surface glycoprotein (vsg). when the duplicated, expressed vsg gene in mvat5-rx2 was compared with its donor (basic copy) gene, 11 nucleotide differences were found in the respective 1.5-kb coding regions (y. lu, t. hall, l. s. gay, and j. e. donelson, cell 72:397-406, 1993). here we describe a char ...19948196636
combination chemotherapy of drug-resistant trypanosoma brucei rhodesiense infections in mice using dl-alpha-difluoromethylornithine and standard trypanocides.combinations of dl-alpha-difluoromethylornithine (dfmo; eflornithine; ornidyl) with either suramin or melarsen oxide were found to be effective against acute laboratory model infections with trypanosoma brucei rhodesiense. we used clinical isolates known to be resistant to these drugs when used singly. an infection with a melarsen oxide-refractory isolate was cured by a combination of low-dose dfmo (0.5% in the drinking water) plus low-dose suramin (1 mg/kg of body weight given intraperitoneally ...19948203855
trypanosoma brucei rhodesiense: the inhibition of hl-60 cell growth by the african trypanosomes in vitro.trypanosomiasis is of major public health importance in africa where the disease affects man and livestock. in order to explore the underlying mechanisms of pathogenesis in african trypanosomiasis, we studied the inhibition of host cell (human promyelocytic hl-60 cells) growth by trypanosoma brucei rhodesiense using an in vitro system. this inhibition was not due to changes in ph or nutritional depletion of the culture medium by the trypanosomes as inhibitory activity was still observed in cultu ...19938224086
suppressor macrophages in african trypanosomiasis inhibit t cell proliferative responses by nitric oxide and prostaglandins.suppression of host t cell responses is one of the hallmarks of infection with the african trypanosomes. the cellular basis for immunosuppression includes the generation of suppressor macrophages that down-regulate t cell proliferative but not necessarily cytokine responses to both mitogen and trypanosome ag. since macrophages from infected animals display activation characteristics, we have asked whether products of activated cells, specifically nitric oxide (no) and pg, may mediate the suppres ...19938228241
thyroid dysfunction in african trypanosomiasis: a possible role for inflammatory cytokines.sleeping sickness (african trypanosomiasis) is an anthropozoonosis transmitted by the tsetse fly. the treatments of choice are the antiparasitic agents suramin and/or melarsoprol. experimental infection of animals with trypanosoma brucei results in inflammatory lesions in the pituitary and/or the thyroid gland. in biochemical terms, these animals have hypothyroidism. we evaluated the functional integrity of the hypothalamic-pituitary-thyroid axis in patients with african trypanosomiasis before, ...19938287572
a colorimetric assay for trypanosome viability and metabolic function.we have adapted a tetrazolium salt (mtt) colorimetric cytotoxicity assay to the assessment of viability and metabolic function in cultured african trypanosomes. trypomastigotes of trypanosoma congolense and t. brucei rhodesianse were harvested from the blood of parasitemic rats and cultured under axenic conditions that support trypanosome viability and growth. analysis of serial dilutions of these bloodstream forms indicated that the assay could detect 10(4) parasites. to assess the effect of ly ...19938291189
isozyme variability of trypanosoma brucei s.l.: genetic, taxonomic, and epidemiological significance.seventy-eight trypanosoma brucei s.l. stocks from different hosts, representing the three trypanosoma brucei subspecies and three trypanosoma evansi stocks, were studied for variation at 18 polymorphic isozyme loci. the results were used to determine the genetic variability among stocks and to estimate gene flow among populations. total genetic variability in t. brucei s.l. was less than that in trypanosoma cruzi, the agent of chagas' disease. results support a clonal population structure in t. ...19948299755
resistance to dl-alpha-difluoromethylornithine by clinical isolates of trypanosoma brucei rhodesiense. role of s-adenosylmethionine.the ornithine decarboxylase (odc) inhibitor dl-alpha-difluoromethylornithine (dfmo) has emerged as a new treatment for west african sleeping sickness but is less effective against east african sleeping sickness. we examined uncloned clinical isolates of trypanosoma brucei rhodesiense, agent of the disease in east africa, which were refractory to dfmo in laboratory infections, for characteristics that would explain their resistance. none of the isolates were from patients treated with dfmo. two i ...19938347171
evaluation of the in vitro transformation technique to distinguish trypanosoma evansi from cyclically transmitted trypanozoon stocks.in order to initiate transformation into procyclic forms, bloodstream trypanosomes, were transferred to semi-defined medium at 27 degrees c. all stocks previously classified as trypanosoma brucei rhodesiense, t.b. gambiense and t.b. brucei transformed into procyclic forms. none of the 31 characterized t. evansi stocks transformed into procyclic forms, but died between day 4 and day 6 in culture. on the other hand, 3 out of 64 stocks of monomorphic brucei subgroup field isolates from camels trans ...19938367656
point mutations are associated with a gene duplication leading to the bloodstream reexpression of a trypanosome metacyclic vsg.african trypanosomes evade the immune response of their hosts by sequentially expressing different variant surface glycoproteins (vsgs). we isolated a bloodstream trypanosome clone of trypanosoma brucei rhodesiense that expresses a vsg normally present during the metacyclic stage of the parasite in the insect vector. associated with the bloodstream reexpression of this metacyclic vsg is a gene conversion in which the duplicated, expressed gene of 1650 nt contains 11 scattered point mutations whe ...19938381717
pharmacokinetic properties of the trypanocidal drug melarsoprol.with a biological assay and atomic absorption spectrometry we determined the level of melarsoprol in the serum and cerebrospinal fluid of 19 patients treated with melarsoprol in daloa, ivory coast. most serum levels were between 2 and 4 micrograms/ml 24 h after administration, and were still > or = 0.1 microgram/ml after 120 h. levels in the cerebrospinal fluid were between 0 and 0.1 microgram/ml. elimination was biphasic, with a pronounced beta 1 phase. mean terminal elimination half-life of me ...19938391966
rickettsia-like organisms and chitinase production in relation to transmission of trypanosomes by tsetse flies.rickettsia-like organisms (rlo) from testse midguts and mosquito cell cultures showed high levels of endochitinase activity. a line of glossina morsitans morsitans highly susceptible to midgut trypanosome infection and with high incidence of rlo infection showed significantly greater chitinolytic activity than g. austeni which had low rlo incidence and were correspondingly refractory to midgut infection. midgut infection rates of trypanosoma brucei rhodesiense in g. m. morsitans showed a dose-re ...19938414668
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