Publications

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 ...	1995	7567957
trypanosoma brucei rhodesiense: variation in human serum resistance after transmission between bushbuck and domestic ruminants by glossina morsitans morsitans.		1995	7572432
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.	1995	7574836
[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 ...	1995	7581198
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 ...	1995	7623216
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 ...	1995	7625108
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 ...	1995	7626112
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 ...	1995	7631128
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 ...	1995	7631129
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 ...	1995	7650918
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). ...	1995	7675533
[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 ...	1995	7477570
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 ...	1995	7479764
the scourge of human african trypanosomiasis.	human african trypanosomiasis (sleeping sickness) is a parasitic disease caused by two different trypanosome subspecies, trypanosoma brucei rhodesiense and t.b. gambiense. each causes a different form of the disease. untreated, the outcome of both infections is death. sleeping sickness occurs exclusively on the african continent, south of the sahara. it is restricted to the distribution area of its vector, glassina or tsetse fly. 36 out of the 52 african countries are considered endemic for slee ...	1995	12319651
the origins, dynamics and generation of trypanosoma brucei rhodesiense epidemics in east africa.	the history of sleeping sickness in east africa has provoked controversy not only about the origins and spread of the disease, but also the identity of the causative organisms involved. molecular methodology(1) has shed new light on the genetic makeup of the organisms involved in recent epidemics. here, geoff hide, andrew tait, ian maudlin and susan welburn discuss these new data in relation to previous theories about the origins of epidemics in east africa which emphasized the importance of the ...	1996	15275254
apoptosis in procyclic trypanosoma brucei rhodesiense in vitro.	apoptosis is a phenomenon previously associated exclusively with metazoan organisms. we show here that procyclic insect form trypanosoma brucei rhodesiense, a protozoan parasite, when treated in vitro with concanavalin a displayed several features normally associated with apoptosis in metazoan cells. lectin treatment induced cleavage of nuclear dna into oligonucleosomal fragments, suggesting activation of an endogenous nuclease in the parasite. treated trypanosomes, although agglutinated and non ...	1996	17180087
in vitro trypanocidal activities of new s-adenosylmethionine decarboxylase inhibitors.	a series of novel aromatic derivatives based on the structure of methylglyoxal bis(guanylhydrazone) (mgbg) was examined for in vitro antitrypanosomal activities and cytotoxicities for human cells. one-third of the compounds tested showed trypanocidal activity at concentrations below 0.5 microm after an incubation period of 72 h. structure-activity analysis revealed that bicyclic compounds with homocyclic rings and unmodified termini were the most active compounds. results obtained in three labor ...	1996	8726017
in vivo trypanocidal activities of new s-adenosylmethionine decarboxylase inhibitors.	a series of novel aromatic derivatives based on the structure of methylglyoxal bis(guanylhydrazone) (mgbg) was examined for trypanocidal activities in human and veterinary trypanosomes of african origin. one agent, cgp 40215a, a bicyclic analog of mgbg which also resembles the diamidines diminazene (berenil) and pentamidine, was curative of infections by 19 isolates of trypanosoma brucei subspecies as well as a trypanosoma congolense isolate. several of these isolates were resistant to standard ...	1996	8726018
evaluation of african medicinal plants for their in vitro trypanocidal activity.	petroleum ether, dichloromethane, methanol and water extracts from 24 plants, belonging to 19 families, which are reported in the literature as traditional remedies for sleeping sickness (human african trypanosomiasis) were screened for in vitro activity against trypanosoma brucei rhodesiense, as well as fro cytotoxicity for a human fibroblast cell-line (wi-38). the trypanocidal activity of the natural compounds berberine and harmane, both documented as being trypanocidal, was also evaluated. pr ...	1996	9121161
elevated serum nitrate in trypanosoma brucei 'rhodesiense' infections: evidence for inducible nitric oxide synthesis in trypanosomiasis.		1996	8882185
metronidazole and suramin combination in the treatment of arsenical refractory rhodesian sleeping sickness--a case study.		1996	8882195
molecular characterization of the kinetoplastid membrane protein-11 from african trypanosomes.	the kinetoplastid membrane protein-11 molecule was purified from trypanosoma brucei rhodesiense and an internal peptide sequence was obtained. this sequence information was used with cosmid library screening and polymerase chain reaction amplifications of both genomic dna and cdna to obtain the entire dna sequence of the encoding gene and the corresponding translated amino acid sequence of 92 residues. the sequence showed 18% divergence from the corresponding molecule of the related kinetoplasti ...	1996	8892307
trypanosoma brucei rhodesiense infection imported to mexico from a tourist resort in kenya.		1996	8909868
antitrypanosomal activity of purine nucleosides can be enhanced by their conversion to o-acetylated derivatives.	fifteen purine nucleosides and their o-acetylated ester derivatives were examined for in vitro antitrypanosomal activity against the lab 110 eatro isolate of trypanosoma brucei brucei and two clinical isolates of trypanosoma brucei rhodesiense. initial comparisons of activity were made for the lab 110 eatro isolate. three nucleoside analogs exhibited no significant activity (50% inhibitory concentrations [ic50s] of > 100 microm), whether they were o acetylated or unacetylated; three nucleosides ...	1996	8913466
molecular characterization of glycosomal nad(+)-dependent glycerol 3-phosphate dehydrogenase from trypanosoma brucei rhodesiense.	the primary structure of a 38-kda protein isolated from membrane preparations of african trypanosomes was determined by protein and dna sequencing. searching of the protein database with the trypanosome translated amino acid sequence identified glycerol 3-phosphate dehydrogenase (ec 1.1.1.8) from various prokaryotic and eukaryotic organisms as the optimal scoring protein. surprisingly, the eukaryotic trypanosome enzyme showed the highest degree of sequence identity with the corresponding enzyme ...	1996	8920003
[human african trypanosomiasis].	human african trypanosomiasis (hat) is caused by infestation with a flagellate protozoan, the trypanosome which is inoculated by the bite of the tsetse fly glossina. the particular ecological conditions of parasites and vectors are such that the disease is only found in the intertropical regions of africa. although there are many species of trypanosomes, only two, belonging to the brucei group are likely to lead to hat. these two species are quite similar morphologically but have different patho ...	1996	8952890
in vitro antitrypanosomal activity of african plants used in traditional medicine in uganda to treat sleeping sickness.	in uganda, as in many other african countries, herbal treatment of various diseases is still common. in the present study, 9 plant species collected from tanzania and uganda and used by traditional healers in southern-eastern uganda for the treatment of human african trypanosomiasis (sleeping sickness) were extracted and screened for their in vitro activity against trypanosoma brucei rhodesiense, one of the two causative agents of sleeping sickness. eight lipophilic extracts of 5 plants revealed ...	1996	8980587
the individual host, a unique evolutionary island for rapidly dividing parasites: a theoretical approach.	it is hypothesized that rapidly dividing parasites producing high parasitemias within an individual host are in different environmental settings. it is further suggested that these infrapopulations experience the drastic environmental changes of free-living forms in an island environment and, that in chronically infected animals, the environmental conditions will over time select the parasites best suited to grow in their changing habitat. evidence is presented to demonstrate that the host envir ...	1996	8604094
differential expression of the expression site-associated gene i family in african trypanosomes.	a minimum of 20 different mrna species encoding related members of the expression site-associated gene i (esag-i) family occur in metacyclic variant antigen type 4 bloodstream trypanosomes. none of these esag-i mrnas are derived from the metacyclic variant antigen type 4 variant surface glycoprotein (vsg) gene expression site, and some appear to come from pseudogenes. the esag-is are transcribed in both procyclic and bloodstream trypanosomes, but their mrnas accumulate to a detectable steady sta ...	1996	8621657
(s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(s)-hpmpa]: a purine analogue with trypanocidal activity in vitro and in vivo.	the unique features of purine salvage systems of pathogenic haemoflagellates render them selectively susceptible to the cytotoxic effects of purine analogues. a series of acyclic nucleoside phosphonates were evaluated for activity against pathogenic haemoflagellates in vitro. one of the phosphonylmethoxyalkylpurines, namely (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(s)-hpmpa], was active in vitro against bloodstream forms of trypanosoma brucei rhodesiense, t. b. gambiense, multidrug-re ...	1996	8665394
hypogonadism in rhodesian sleeping sickness: evidence for acute and chronic dysfunction of the hypothalamic-pituitary-gonadal axis.	to investigate acute and long-term effects of rhodesian sleeping sickness on the function of the hypothalamic-pituitary-gonadal (hpg) axis in men.	1996	8557157
susceptibility of ugandan trypanosoma brucei rhodesiense isolated from man and animal reservoirs to diminazene, isometamidium and melarsoprol.	thirty-six trypanosoma brucei spp. stocks isolated from man and domestic animals in south-east uganda were studied for susceptibility to diminazene, isometamidium and melarsoprol in vitro. all stocks were susceptible to melarsoprol. one t.b. rhodesiense stock isolated from a sleeping sickness patient showed reduced susceptibility to the veterinary drugs diminazene and isometamidium. more than 100 ng/ml diminazene or 0.78 ng/ml isometamidium were required to eliminate that stock during 10 days dr ...	1997	9018298
mechanism of resistance of african trypanosomes to cytotoxic human hdl.	trypanosoma brucei brucei, the causative agent of ngana in cattle, is non-infectious to humans because of its sensitivity to the cytolytic activity of normal human serum. the toxin in normal human serum is human haptoglobin-related protein (hpr) which is found either as an apolipoprotein associated with a minor subclass of high-density lipoprotein (hdl), named trypanosome lytic factor (tlf1), or as an unstable, high-molecular-mass protein complex known as tlf2 (refs 5, 9-12). tlf-mediated lysis ...	1997	9039915
(+)-7-deaza-5'-noraristeromycin as an anti-trypanosomal agent.	the (+)-enantiomer of 7-deaza-5'-noraristeromycin (4) has been found to show ic50 values ranging from 0.16 to 5.3 microm against four strains of african trypanosomes, one trypanosoma brucei brucei isolate, and several clinical isolates of trypanosoma brucei rhodesiense (agent of east african sleeping sickness), including a multidrug resistant clone of one isolate. while this compound was originally designed to inhibit s-adenosyl-l-homocysteine hydrolase, it has been found to have no effect on th ...	1997	9046353
synthesis and anti-trypanosomal activity of various 8-aza-7-deaza-5'noraristeromycin derivatives.	a recent observation that (+)-7-deaza-5'-noraristeromycin (1), as an l-like analogue of aristeromycin, possessed meaningful anti-trypanosomal properties has prompted a search of other 7-deazapurines with similar or improved anti-trypanosomal responses. in that direction a series of pyrazolo[3,4-d]pyrimidines (that is, 8-aza-7-deaza-5'-noraristeromycin derivatives, 2-11) related to 1 have been prepared. these derivatives were evaluated against bloodstream forms of trypanosoma brucei brucei and tr ...	1997	9046354
a unique transporter of s-adenosylmethionine in african trypanosomes.	african trypanosomes are pathogens of humans and livestock in equatorial africa. there is a great deal of resistance to present front line drugs for treating african trypanosomiasis such as melarsoprol (arsobal) and pentamidine. in the search for new and novel drugs against this disease, we have found a unique transporter of s-adenosylmethionine (adomet), a metabolite used in transmethylation reactions and polyamine synthesis. this transporter is distinct from those for methionine and adenosine, ...	1997	9068614
a survey of the trypanosoma brucei rhodesiense genome using shotgun sequencing.	a comparison of the efficiency of sequencing random genomic dna fragments versus random cdnas for the discovery of new genes in african trypanosomes was undertaken. trypanosome dna was sheared to a 1.5-2.5 kb size distribution, cloned into a plasmid and the sequences at both ends of 183 cloned fragments determined. sequences of both kinetoplast and nuclear dna were identified. new coding regions were discovered for a variety of proteins, including cell division proteins, an rna-binding protein a ...	1997	9084037
detection of phenoloxidase activity in the hemolymph of tsetse flies, refractory and susceptible to infection with trypanosoma brucei rhodesiense.		1997	9170349
heritability of the trait for human infectivity in genetic crosses of trypanosoma brucei ssp.		1997	9196780
in vitro trypanocidal activity of some rare tanzanian medicinal plants.	extracts prepared from 15 rare tanzanian medicinal plants were tested for their in vitro antitrypanosomal activity against human pathogenic trypanosomes (trypanosoma brucei rhodesiense). of 37 extracts investigated, two were found to have strong activity with ic50 values below 1 microgram/ml and ten extracts revealed promising activities with ic50 values between 1-5 micrograms/ml.	1997	9227800
attempt to correlate urine arsenic excretion with clinical course during melarsoprol therapy of patients with rhodesian trypanosomiasis.	this study enrolled 28 cns-involved patients with trypanosoma brucei rhodesiense at the kenya trypanosomiasis research institute (alupe, kenya) to examine treatment efficacy and toxicity of melarsoprol in relation to renal excretion/dose relationships. this study complied with world health organization treatment recommendations, initially treating with suramin followed by three courses of melarsoprol. traced study patients had a relapse rate of 4.1%. the toxicity and crude death rate was 7.1%. t ...	1997	9230794
in vitro trypanocidal activity of some rare tanzanian medicinal plants.	extracts prepared from 15 rare tanzanian medicinal plants were tested for their in vitro antitrypanosomal activity against human pathogenic trypanosomes (trypanosoma brucei rhodesiense). of 37 extracts investigated, two were found to have strong activity with ic50 values below 1 microgram/ml and ten extracts revealed promising activities with ic50 values between 1 and 5 micrograms/ml.	1997	9241382
a proposed density-dependent model of long slender to short stumpy transformation in the african trypanosomes.	a simple arithmetic model is developed that is based upon the assumption: (1) that transformation of replicating long slender trypanosoma brucei to nonreplicating short stumpy forms is parasite population density dependent; (2) that as the slender population increases there is a change in the external environment that triggers the slender to stumpy transformation; and (3) that stumpy forms of t. brucei do not induce the change in external environment that triggers slender to stumpy transformatio ...	1997	9267408
alterations in ornithine decarboxylase characteristics account for tolerance of trypanosoma brucei rhodesiense to d,l-alpha-difluoromethylornithine.	ornithine decarboxylase (odc), the target enzyme of d,l-alpha-difluoromethylornithine (dfmo), was investigated in four dfmo-tolerant trypanosoma brucei rhodesiense isolates from east africa and two dfmo-susceptible t. b. gambiense isolates from west africa. neither drug uptake nor inhibition of odc activity by dfmo in cellular extracts differed in the two trypanosome subspecies. however, the specific odc activity of the cellular extracts was three times as high in t. b. rhodesiense isolates as i ...	1997	9303385
co-duplication of a variant surface glycoprotein gene and its promoter to an expression site in african trypanosomes.	activation of the metacyclic variant antigen type 7 (mvat7) variant surface glycoprotein (vsg) gene in bloodstream trypanosoma brucei rhodesiense involves a duplicative transposition of the gene. the dna transposition unit extends from a site approximately 3.0 kilobases upstream of the vsg gene through the coding region and includes a 73-base pair sequence that possesses promoter activity in transient transfections. this mvat7 promoter has 80% identity to a previously characterized promoter for ...	1997	9305933
in vivo efficacies of 5'-methylthioadenosine analogs as trypanocides.	5'-deoxy-5'-(methylthio)adenosine (mta), a key by-product of polyamine biosynthesis, is cleaved by mta phosphorylase and is salvaged as adenine and, through conversion of the ribose moiety, methionine. an analog of mta, 5'-deoxy-5'-(hydroxyethylthio)adenosine (heta), is a substrate for trypanosome mta phosphorylase and is active in vitro and in vivo against trypanosoma brucei brucei, an agent of bovine trypanosomiasis. in this study, heta and three o-acylated heta derivatives were examined for t ...	1997	9333033
african trypanosomes have differentially expressed genes encoding homologues of the leishmania gp63 surface protease.	the genomes of various leishmania parasites contain tandemly arrayed genes encoding an abundant 63-kda surface glycoprotein called gp63. leishmania gp63s are metalloproteases that play an important role in the invasion and survival of the parasites within the macrophage, and their presence on the leishmania surface has been correlated with resistance to complement-mediated lysis. here we report the identification of gp63-like genes in african trypanosomes. the predicted trypanosome and leishmani ...	1997	9334260
human african trypanosomiasis: mri.	we report a case of human african trypanosomiasis caused by trypanosoma brucei rhodesiense. after the febrile period of parasite dissemination, the patient had meningeal involvement but normal ct. mri showed the appearances of meningitis. after two periods of arsenical treatment, a severe encephalopathy occurred suggesting post-therapeutic reactive encephalitis (ptre). nevertheless, t2-weighted mri showed no oedema, but focal bilateral high signal areas in the white matter. ptre was excluded and ...	1997	9351106
the alamar blue assay to determine drug sensitivity of african trypanosomes (t.b. rhodesiense and t.b. gambiense) in vitro.	alamar blue, an indicator for metabolic cell function, was evaluated as a fluorescent and as a colorimetric dye in drug sensitivity assays for human pathogenic african trypanosomes, trypanosoma brucei rhodesiense and t.b. gambiense. the experimental conditions were adjusted to find those where the relationship between trypanosome number and alamar blue signal was linear over the widest possible range. fluorescent signals correlated to trypanosome numbers from 10(4) trypanosomes/ml (t.b. rhodesie ...	1997	9386789
tryptect ciatt--a card indirect agglutination trypanosomiasis test for diagnosis of trypanosoma brucei gambiense and t. b. rhodesiense infections.	a simple and rapid test, the card indirect agglutination trypanosomiasis test (tryptect ciatt) is described, for detecting circulating antigens in persons suffering from trypanosoma brucei gambiense and t. b. rhodesiense infection by latex agglutination. the sensitivity of the test (95.8% for t. b. gambiense and 97.7% for t. b. rhodesiense) was significantly higher than that of lymph node puncture, microhaematocrit centrifugation and cerebrospinal fluid examination after single and double centri ...	1997	9463665
genetic diversity among trypanosoma brucei rhodesiense isolates from tanzania.	we compared 19 stocks of trypanosoma brucei rhodesiense collected in 1991 and 1994 from tanzania with representative stocks from other foci of rhodesian sleeping sickness in zambia, kenya and uganda. stocks were characterized by isoenzyme electrophoresis, restriction fragment length polymorphisms in variant surface glycoprotein genes and random amplification of polymorphic dna; the banding patterns obtained were coded for numerical analysis. in addition, the tanzanian stocks were compared by pul ...	1997	9488868
duration of symptoms and case fatality of sleeping sickness caused by trypanosoma brucei rhodesiense in tororo, uganda.	although there have been recent molecular biological studies for evidence of possible changes in trypanosome biochemistry, such studies are not yet complemented by parallel clinical studies to determine the possible implications to the sleeping sickness patient. the study of the duration of symptoms and the case fatality of t. b. rhodesiense showed that the disease progressed to the stage of central nervous system involvement between three weeks to two months of infection. most (> 80%) deaths oc ...	1997	9557424
programmed cell death in procyclic trypanosoma brucei rhodesiense is associated with differential expression of mrnas.	procyclic trypanosoma brucei rhodesiense have a cell death mechanism which can be activated by an external signal, the lectin cona, in vitro. cona has been shown to cause profound changes in cellular morphology and induce fragmentation of nuclear dna in t.b. rhodesiense which are characteristic of apoptosis, a form of programmed cell death (pcd) in other eukaryotic cells. rna analysis of trypanosomes induced to undergo pcd revealed that rna remains intact up to 48 h into the process, a time when ...	1997	16465255
a multi-centre evaluation of the card indirect agglutination test for trypanosomiasis (tryptect ciatt).	a version of the card indirect agglutination test for trypanosomiasis, the tryptect ciatt, was evaluated for the diagnosis of trypanosoma brucei gambiense and t. b. rhodesiense sleeping sickness. the results of this antigen-detection test indicated high relative sensitivity (99.3%) and specificity (99.4%), and also much higher prevalences of infection in the general population of endemic foci (27.9% for t. b. gambiense and 21.8% for t. b. rhodesiense) than detected by parasitological diagnosis ( ...	1998	10396343
antitrypanosomal effects of traditional chinese herbal medicines on bloodstream forms of trypanosoma brucei rhodesiense in vitro.	the antitrypanosomal activity of traditional chinese herbal medicines and these crude drug ingredients were determined using axenic cultured bloodstream forms of trypanosoma b. rhodesiense which is one of the two causative agents of african sleeping sickness in man. the drugs tested were 8 traditional chinese herbal medicines and these 14 crude drug ingredients. of these traditional chinese medicines examined, san'o-shasin-to and oren-gedoku-to showed most potent antitrypanosomal effect. the min ...	1998	10437965
characterization of a relatively rare class b, type 2 trypanosome variant surface glycoprotein gene.	the variant surface glycoprotein (vsg) gene of trypanosoma brucei rhodesiense loutat 1.5, a defined african trypanosome variant antigenic type, was cloned and sequenced. southern blot analysis revealed 2 dna restriction fragments in both vsg 1.5 expressor and nonexpressor populations, suggesting that there are 2 genomic copies of the vsg 1.5 gene and no expression-linked copies. pulsed-field gel electrophoresis followed by southern blot analysis showed that each copy of the vsg 1.5 gene exists o ...	1998	9576500
total synthesis and biological activities of (+)- and (-)-boscialin and their 1'-epimers.	natural (-)-boscialin [(-)-1] has recently been described as one of the constituents of various medicinal plants. to obtain more material for investigations of its biological activities, we carried out the synthesis of (-)-1 and its isomers. starting from the chiral building block 2, the key steps of the synthesis involved a regioselective reduction and a nucleophilic addition. the enantiomer of the natural product, (+)-boscialin [(+)-1], could be obtained via acid-catalyzed epimerization of hyd ...	1998	9599255
trypanosoma brucei: comparison of circulating strains in an endemic and an epidemic area of a sleeping sickness focus.	human sleeping sickness in east africa is characterized by periods of long-term endemicity interspersed with short-term epidemics. the factors generating these huge changes are largely uncharacterized but probably reflect complex interactions among socioeconomic factors, ecological factors, and the movement and diversity of trypanosome strains. to investigate the role of trypanosome strains in the generation of these epidemics, we addressed two important questions. (1) are the trypanosome strain ...	1998	9603485
response of a t. b. rhodesiense stock with reduced drug susceptibility in vitro to treatment in mice and cattle.	in vivo drug susceptibility tests involving treatment of infected mice and cattle were performed on two trypanosome stocks, a t. brucei brucei and a t.b. rhodesiense, isolated in south eastern uganda. the t. b. rhodesiense stock had expressed reduced susceptibility to diminazene aceturate and isometamidium chloride in vitro, while the other, a t. b. brucei stock was susceptible. diminazene aceturate at 14 mg/kg was not sufficient to cure all t. b. rhodesiense infected mice. similarly, in the cas ...	1998	9638278
arrest of trypanosoma brucei rhodesiense and t. brucei brucei in the s-phase of the cell cycle by (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine ((s)-hpmpa).	african trypanosomes are incapable of purine de novo synthesis. they use salvage pathways to meet their purine requirements. therefore, purine analogues appear as potential candidates to interfere in trypanosome metabolism. the acyclic adenosine analogue (s)-9-(-3-hydroxy-2-phosphonylmethoxypropyl)adenine ((s)-hpmpa) expressed antitrypanosomal activity in vitro and vivo. when exposed to 20 microm (s)-hpmpa, trypanosomes were arrested in the s-phase of the cell cycle and were unable to enter g2-p ...	1998	9662031
trypanosome infections and survival in tsetse.	the effect of trypanosome infection on vector survival was observed in a line of glossina morsitans selected for susceptibility to trypanosome infection. the differential effects of midgut and salivary gland infections on survival were examined by exposing flies to infection with either trypanosoma congolense which colonizes midgut and mouthparts or trypanosoma brucei rhodesiense which colonizes midgut and salivary glands. a comparison of the survival distributions of uninfected flies with those ...	1998	9695107
effects of intermediates of methionine metabolism and nucleoside analogs on s-adenosylmethionine transport by trypanosoma brucei brucei and a drug-resistant trypanosoma brucei rhodesiense.	the effects of purine nucleoside analogs, polyamines, and established trypanocidal agents on the uptake of [8-14c]adenosine and s-[methyl-3h]adenosylmethionine (adomet) by bloodform trypanosomes of drug-susceptible trypanosoma brucei brucei and a drug-resistant trypanosoma brucei rhodesiense clinical isolate were compared. adomet uptake was not antagonized by omithine or methionine (500 microm), adenosine (100 microm), or other purine nucleosides, including methylthioadenosine (mta) at 500 micro ...	1998	9698093
bioassay-guided isolation of a diastereoisomer of kolavenol from entada abyssinica active on trypanosoma brucei rhodesiense.	bioassay-guided fractionation of the dichloromethane rootbark extract of entada abyssinica (leguminosae), a plant used by traditional healers in uganda for the treatment of sleeping sickness, led to the isolation of a diastereoisomer of the clerodane type diterpene kolavenol. this is the first report on this compound. it showed a trypanocidal activity with an ic50 value of 2.5 microg/ml (8.6 microm) against trypanosoma brucei rhodesiense, the causing agent of the acute form of human african tryp ...	1998	9705008
antitrypanosomal activity of a new triazine derivative, sipi 1029, in vitro and in model infections.	a recently developed diaminotriazine derivative [o,o'-bis(1, 2-dihydro-2,2-tetramethylene-4,6-diamino-s-triazin-1-yl)-1, 6-hexanediol dihydrochloride; t-46; sipi 1029] was examined for activity against african trypanosomes in in vitro and in vivo model systems. in vitro, sipi 1029 was 50% inhibitory for growth of bloodstream trypomastigotes of four strains of trypanosoma brucei brucei and trypanosoma brucei rhodesiense at 0.15 to 2.15 nm (50% inhibitory concentrations). in in vivo mouse laborato ...	1998	9756783
molecular cloning and expression of a purine-specific n-ribohydrolase from trypanosoma brucei brucei. sequence, expression, and molecular analysis.	n-ribohydrolases, including the inosine-adenosine-guanosine-preferring (iag) nucleoside hydrolase, have been proposed to be involved in the nucleoside salvage pathway of protozoan parasites and may constitute rational therapeutic targets for the treatment of these diseases. reported is the complete sequence of the trypanosoma brucei brucei iagnh gene, which encodes iag-nucleoside hydrolase. the 1.4-kilobase iagnh cdna contains an open reading frame of 981 base pairs, corresponding to 327 amino a ...	1998	9442052
interleukin-4-dependent immunoglobulin g1 isotype switch in the presence of a polarized antigen-specific th1-cell response to the trypanosome variant surface glycoprotein.	this study examines b-cell immunoglobulin (ig) class-switching events in the context of parasite antigen-specific th-cell responses in experimental african trypanosomiasis. inbred mice were infected with trypanosoma brucei rhodesiense, and the coordinate stimulation of th-cell cytokine responses and b-cell responses to the trypanosome variant surface glycoprotein (vsg) was measured. the cytokines produced by t cells in response to vsg, at both the transcript and protein levels, were gamma interf ...	1998	9453595
prohibitin and rack homologues are up-regulated in trypanosomes induced to undergo apoptosis and in naturally occurring terminally differentiated forms.	two genes have been identified as up-regulated late during cona-induced apoptosis in procyclic form trypanosoma brucei rhodesiense. the first represents a homologue of prohibitin, a proto-oncogene originally described in mammals and subsequently in yeast, which is involved in cell-cycle control and senescence. the trypanosoma prohibitin homologue appears to contain within it a putative death domain. the second gene, homologous to a family of regulatory proteins which are receptors for activated ...	1998	10200516
in vitro and in vivo activities of trybizine hydrochloride against various pathogenic trypanosome species.	trybizine hydrochloride [o,o'-bis(4,6-diamino-1,2-dihydro-2, 2-tetramethylene-s-triazine-1-yl)-1,6-hexanediol dihydrochloride] was active in vitro against the sleeping sickness-causing agents trypanosoma brucei subsp. rhodesiense and t. brucei subsp. gambiense; against a multidrug-resistant organism, t. brucei subsp. brucei; and against animal-pathogenic organisms trypanosoma evansi, trypanosoma equiperdum, and trypanosoma congolense; but not against the intracellular parasites trypanosoma cruzi ...	1998	9797216
human african trypanosomiasis: an emerging public health crisis.	there is a dramatic resurgence of human african trypanosomiasis (hat) in sub-saharan africa. t.b. gambiense is spreading epidemically in large areas of central africa, especially the southern sudan, congo-zaire, angola, uganda and the central african republic. devastating epidemics of t.b. rhodesiense have occurred in south-eastern uganda. the causes of the re-emergence of sleeping sickness as a public health problem include widespread civil disturbance and war, declining economies, reduced heal ...	1998	9830201
treatment of late stage rhodesiense trypanosomiasis using suramin and eflornithine: report of six cases.		1998	9850406
generation of expressed sequence tags as physical landmarks in the genome of trypanosoma brucei.	previous molecular genetic studies on the african trypanosome have focused on only a few genes and gene products, the majority of which are concerned with surface antigenic variation; consequently, an insignificant number of the genes of this organism have been characterized to date. in order to: (1) identify new genes and analyze their expression profile, (2) generate expressed sequence tags (ests) for derivation of a physical map of the trypanosome genome, and (3) make available the partial se ...	1998	9852954
resistance to the african trypanosomes is ifn-gamma dependent.	the role of variant surface glycoprotein (vsg)-specific th cell responses in determining resistance to the african trypanosomes was examined by comparing th cell responses in relatively resistant and susceptible mice as well as in cytokine gene knockout mice infected with trypanosoma brucei rhodesiense. resistant b10.br and c57bl/6 mice expressed th1 cell cytokine responses to vsg stimulation during infection, while susceptible c3h mice produced weak or no th1 cell cytokine responses. neither re ...	1998	9862708
a vsg expression site-associated gene confers resistance to human serum in trypanosoma rhodesiense.	infectivity of trypanosoma brucei rhodesiense to humans is due to its resistance to a lytic factor present in human serum. in the etat 1 strain this character was associated with antigenic variation, since expression of the etat 1.10 variant surface glycoprotein was required to generate resistant (r) clones. in addition, in this strain transcription of a gene termed sra was detected in r clones only. we show that the etat 1.10 expression site is the one selectively transcribed in r variants. thi ...	1998	9865701
metabolic effects of a methylthioadenosine phosphorylase substrate analog on african trypanosomes.	the effects of 5'-deoxy-5'-(hydroxyethylthio)adenosine (heta), a trypanocidal analog of 5'-deoxy-5'-(methylthio)adenosine (mta), on polyamine synthesis and s-adenosylmethionine (adomet) metabolism were examined in bloodstream forms of trypanosoma brucei brucei. heta was cleaved by trypanosome mta phosphorylase at the same rate as the natural substrate, mta, in a phosphate-dependent reaction. fluorine substitution at the 2-position of the purine ring increased activity by approximately 50%, where ...	1999	9920289
ifn-gamma-dependent nitric oxide production is not linked to resistance in experimental african trypanosomiasis.	resistance to african trypanosomes is dependent on b cell and th1 cell responses to the variant surface glycoprotein (vsg). while b cell responses to vsg control levels of parasitemia, the cytokine responses of th1 cells to vsg appear to be linked to the control of parasites in extravascular tissues. we have recently shown that ifn-gamma knockout (ifn-gamma ko) mice are highly susceptible to infection and have reduced levels of macrophage activation compared to the wild-type c57bl/6 (wt) parent ...	1999	10066343
kinetics of s-adenosylmethionine cellular transport and protein methylation in trypanosoma brucei brucei and trypanosoma brucei rhodesiense.	african trypanosomes of the trypanosoma brucei group are agents of disease in man and animals. they present unique biochemical characteristics such as the need for preformed purines and have extensive salvage mechanisms for nucleoside recovery. in this regard we have shown that trypanosomes have a dedicated transporter for s-adenosylmethionine (adomet), a key metabolite in transmethylation reactions and polyamine synthesis. in this study we compared the apparent kinetics of adomet transport, cyt ...	1999	10087160
programmed cell death in procyclic form trypanosoma brucei rhodesiense --identification of differentially expressed genes during con a induced death.	trypanosoma brucei rhodesiense can be induced to undergo apoptosis after stimulation with con a. as cell death in these parasites is associated with de novo gene expression we have applied a differential display technique, randomly amplified differential expressed sequence-polymerase chain reaction (rades-pcr) to the study of gene expression during con a induced cell death in these organisms. twenty-two differentially displayed products have been cloned and sequenced. these represent the first e ...	1999	10224534
the anatomy and transcription of a monocistronic expression site for a metacyclic variant surface glycoprotein gene in trypanosoma brucei.	african trypanosomes evade the immune response of their mammalian hosts by switching the expression of their variant surface glycoprotein genes (vsg). the bloodstream trypanosome clone mvat4 of trypanosoma brucei rhodesiense expresses a metacyclic vsg as a monocistronic rna from a promoter located 2 kilobases (kb) upstream of its start codon. determination of 23 kb of sequence at the metacyclic variant antigen type 4 (mvat) vsg expression site (es) revealed an es-associated gene (esag) 1 precede ...	1999	10358033
inhibition of succinyl coa synthetase histidine-phosphorylation in trypanosoma brucei by an inhibitor of bacterial two-component systems.	recent drug screenings for new antibacterial drugs directed against histidine phospho-relay signalling pathways in bacteria have resulted in compounds which potently inhibit the histidine kinase activity of bacterial two-component systems. the present study demonstrates that one of these compounds, ly266500, is also a potent inhibitor of histidine phosphorylation in the unicellular eukaryotic parasite trypanosoma brucei, both in vitro and in whole cells. in vitro, it inhibits histidine phosphory ...	1999	10376993
[melarsoprol].		1999	10816741
trypanosomosis agglutination card test for trypanosoma brucei rhodesiense sleeping sickness.	to develop a simple field test for diagnosis of trypanosoma brucei rhodesiense in man.	1999	10442147
plasma nitrate and interferon-gamma in trypanosoma brucei rhodesiense infections: evidence that nitric oxide production is induced during both early blood-stage and late meningoencephalitic-stage infections.		1999	10450441
tsetse-trypanosome interactions: rites of passage.	trypanosomes that cause sleeping sickness (trypanosoma brucei rhodesiense and t. b. gambiense) are entirely dependent on tsetse for their transmission between hosts, but the flies are not easily infected. this situation has not arisen by chance - the tsetse has evolved an efficient defence system against trypanosome invasion. in this review, susan welburn and ian maudlin chart the progress of trypanosomes through the fly and identify some of the hazards faced by both parasite and fly that affect ...	1999	10481151
activity of extracts and naphthoquinones from kigelia pinnata against trypanosoma brucei brucei and trypanosoma brucei rhodesiense.	dichloromethane extracts of the root bark and stem bark of kigelia pinnata collected from zimbabwe exhibited antitrypanosomal activity against trypanosoma brucei brucei in vitro. activity-guided fractionation led to the isolation of four naphthoquinones from both the root and stem bark of the plant. the compounds were identified as 2-(1-hydroxyethyl)-naphtho[2,3-b]furan-4,9-quinone (1), isopinnatal (2), kigelinol (3), and isokigelinol (4). subsequently, the compounds were assessed for antitrypan ...	1999	10483374
rhodesian trypanosomiasis in a splenectomized patient.	we report the first apparent case of a splenectomized individual who developed severe trypanosomiasis with central nervous system involvement. the patient was a 41-year-old man who participated in an east african safari. upon his return to the united states, the patient presented with an infection with trypanosoma brucei rhodesiense that was treated successfully with suramin and melarsoprol. the onset of symptoms, laboratory studies, and disease progression did not differ from previously reporte ...	1999	10497985
a revised arithmetic model of long slender to short stumpy transformation in the african trypanosomes.	an arithmetic model that closely approximates an african trypanosome infection in immunosuppressed mice is presented. the final model was based on an examination of the following parameters: the rate of long slender to short stumpy transition, the maximum percentage of long slender to short stumpy stages that can be induced, the survival time or half life of the short stumpy stage in vivo, and the rate (%) of long slender to short stumpy stage transition following the peak in transformation. the ...	1999	10577719
molecular characterisation of trypanosoma brucei alkyl dihydroxyacetone-phosphate synthase.	alkyl dihydroxyacetone-phosphate synthase is the second enzyme of the ether-lipid biosynthetic pathway which is responsible for the introduction of the ether linkage between a fatty alcohol and a glycerol present in a subclass of phospholipids, the plasmalogens and possibly in glycolipid membrane anchors. in this study the gene coding for alkyl dihydroxyacetone-phosphate synthase was isolated from trypanosoma brucei. southern blot analysis of total genomic dna suggested the presence of a single ...	1999	10589981
expression and localization of serum resistance associated protein in trypanosoma brucei rhodesiense.	the trypanosome lytic factor (tlf) is a primate specific innate defense mechanism that restricts the host range of african trypanosomes. trypanosoma brucei rhodesiense, the causative agent of the acute form of human sleeping sickness, is resistant to the cytolytic action of tlf. by differential display pcr we have identified a gene in t. b. rhodesiense that is preferentially expressed in cell lines resistant to tlf. the protein sequence predicted from the gene shows homology to the trypanosome v ...	1999	10593181
evidence for the occurrence of trypanosoma brucei rhodesiense sleeping sickness outside the traditional focus in south-eastern uganda.	the occurrence of trypanosoma brucei rhodesiense west of the river nile, in masindi district in the mid-western part of uganda, is confirmed. masindi borders the traditional belt of t. b. gambiense infection in the north-west, gulu in the north and the democratic republic of congo in the west. of the 702 persons tested for sleeping sickness in masindi, 113 (16%) were positive by the card agglutination test for trypanosomiasis (catt). trypanosomes were observed in samples of cerebrospinal fluid ( ...	1999	10715675
kinetics of methionine transport and metabolism by trypanosoma brucei brucei and trypanosoma brucei rhodesiense.	methionine is an essential amino acid for both prokaryotic and eukaryotic organisms; however, little is known concerning its utilization in african trypanosomes, protozoa of the trypanosoma brucei group. this study explored the michaelis-menten kinetic constants for transport and pool formation as well as metabolic utilization of methionine by two divergent strains of african trypanosomes, trypanosoma brucei brucei (a veterinary pathogen), highly sensitive to trypanocidal agents, and trypanosoma ...	2000	10775440
a new bioactive sesterterpene and antiplasmodial alkaloids from the marine sponge hyrtios cf. erecta.	from the ch(2)cl(2) extract of the sponge hyrtios cf. erecta, collected from fiji, two new sesterterpenes, 1 and 2, and the known compounds isodehydroluffariellolide (3), homofascaplysin a (4), and fascaplysin (5) were isolated. the structures of 1-5 were established employing 1d and 2d nmr spectroscopy and mass spectrometry. all nmr resonances of fascaplysin (5) have been unambiguously assigned. evaluation of the biological activity of the extracts and pure compounds toward plasmodium falciparu ...	2000	10869210
fulminant disease simulating bacterial sepsis with disseminated intravascular coagulation after a trip to east africa.		2000	10923746
african sleeping sickness returns to uk after four years.		2000	11073504
minisatellite marker analysis of trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures.	the african trypanosome, trypanosoma brucei, has been shown to undergo genetic exchange in the laboratory, but controversy exists as to the role of genetic exchange in natural populations. much of the analysis to date has been derived from isoenzyme or randomly amplified polymorphic dna data with parasite material from a range of hosts and geographical locations. these markers fail to distinguish between the human infective (t. b. rhodesiense) and nonhuman infective (t. b. brucei) "subspecies" s ...	2000	11078512
[value of molecular biology in the identification of trypanosomes responsible for african trypanosomiasis or sleeping sickness].		2000	11100432
cytochrome oxidase subunit vi of trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both rna and protein levels.	mitochondrial respiration in the african trypanosome undergoes dramatic developmental stage regulation. this requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. as a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit vi (coxvi). by generati ...	2001	11136449
sleeping sickness: a tale of two diseases.	sleeping sickness presents clinically as two distinct diseases, reflecting the fact that two very different trypanosomes are responsible. the african rift separating east and west africa defines the distribution of the two diseases. in this review, susan welburn, eric fèvre, paul coleman, martin odiit and ian maudlin discuss the biology and distribution of these two diseases in relation to the evolution of hominids in africa.	2001	11137736
new drugs for the treatment of human african trypanosomiasis: research and development.	chemotherapy of human african trypanosomiasis is problematic because of the high frequency of severe adverse events, the long duration and high cost of treatment, and an increasing number of treatment-refractory cases. new cost-efficient, easy-to-use drugs are urgently needed. whereas basic research on potential drug targets is anchored in academia, the complex, highly regulated and very expensive process of preclinical and clinical drug development is almost exclusively in the hands of pharmace ...	2001	11137740
in situ kinetic characterization of methylthioadenosine transport by the adenosine transporter (p2) of the african trypanosoma brucei brucei and trypanosoma brucei rhodesiense.	african trypanosomes are parasitic flagellates that live in the connective tissues of the host. trypanosomes must obtain from their host adenine/adenosine and other nucleosides that can be salvaged through enzymatic cleavage. methylthioadenosine (mta) is a byproduct of polyamine metabolism, formed from the donation of an aminopropyl moiety by decarboxylated s-adenosylmethionine (dcadomet) to form spermidine. mta is then cleaved phosphorolytically by mta phosphorylase to methylthioribose-1-phosph ...	2001	11226379
recombining trypanosome genetics.		2001	11228006