Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
modification of telomeric dna in trypanosoma brucei; a role in antigenic variation?expression of surface antigen genes in trypanosoma brucei occurs at expression sites located near telomeres. since only one antigen is produced at a time, a mechanism must exist to prevent the simultaneous activity of multiple expression sites. here we report that psti and pvuii restriction sites in silent telomeric antigen genes are partially uncleavable , presumably as a consequence of dna modification. the modification, which is absent in transcribed genes but returns after gene inactivation, ...19846328412
characterization of the 1.35 kilobase dna repeat unit containing the conserved 35 nucleotides at the 5'-termini of variable surface glycoprotein mrnas in trypanosoma brucei.we have cloned and determined the sequence of the 1.35 kb trypanosome dna repeat unit that contains the conserved 35 nucleotides found at the 5'-ends of variable surface glycoprotein (vsg) mrnas and present in many other trypanosome rnas. our data indicate that the genomic repeats, estimated by others to be present in 200-250 copies in the haploid genome (18, 21), are structurally very highly conserved but with dispersed point changes. the 1.35 kb repeat unit has an unusual stretch of multiple r ...19846330689
expression of a trypanosoma brucei brucei variant antigen in escherichia coli.a cdna library derived from antigenically homogeneous bloodstream stage trypanosoma brucei brucei was screened with an antiserum directed against the variant surface antigen (vsa) using an enzyme-linked filter immunoassay. several recombinant clones were detected and the clone giving the most intense reaction was further analyzed. it contained a vsa-specific cdna insert and synthesized a protein of the expected molecular weight bearing vsa determinants. the nucleotide sequence of the insert was ...19846366543
the 5'-limit of transposition and upstream barren region of a trypanosome vsg gene: tandem 76 base-pair repeats flanking (taa)90.we have cloned and sequenced a portion of the region upstream of an expressed vsg gene of trypanosoma brucei. this "expression-linked copy" arose through the duplication and transposition of a silent, "basic copy" of the gene to an expression site. comparison of the sequences surrounding the 5'-end of the transposed segment in the two loci indicates the 5'-limit of transposition lies within the first (3'-most) of three repeated segments found at this position in the basic copy locus. these highl ...19846324125
two mechanisms of expression of a predominant variant antigen gene of trypanosoma brucei.african trypanosomes evade the host immune response by periodically switching their variant surface glycoprotein (vsg) coat. the resulting, serologically distinct variant antigenic types (vats) appear in a loosely ordered sequence and those arising early in infections are termed predominant vats. vat switching reflects the successive transcriptional activation of single vsg genes from a large repertoire. activation of some vsg genes is accomplished by duplication of a previously silent basic cop ...19846325951
complete nucleotide sequence of an unusual mobile element from trypanosoma brucei.the complete nucleotide sequence of a mobile element from trypanosoma brucei is presented along with the sequence of its target site, which shows that the insertion has generated a 7 base pair direct repeat. the cloned copy of the element is a dimeric structure, one end of each monomer consisting of a stretch of 14 a residues preceded by a putative trypanosome polyadenylation signal. six base pairs of dna of unknown origin are found in the dimer between the two copies of the element. evidence su ...19846327058
arsenic and old taxa: subspeciation and drug sensitivity in trypanosoma brucei.resistance to the trypanocidal drugs atoxyl and tryparsamide was traditionally considered to be a diagnostic feature of rhodesian sleeping sickness and, consequently, of trypanosoma rhodesiense. in examining the tryparsamide sensitivity of 13 isoenzymically defined stocks of the subgenus trypanozoon, typical west african stocks showed no greater drug sensitivity than did those of east and central africa. the greatest resistance to tryparsamide was shown by two stocks isolated in the ivory coast. ...19846241967
the acquisition of human serum resistance during cyclical passage of a trypanosoma brucei brucei clone through glossina morsitans morsitans maintained on human serum. 19846464124
histopathological findings in mini-pigs infected with different strains of trypanosoma brucei.two pigs infected with trypanosoma brucei gambiense developed low parasitemia which became undetectable after 6 months; on autopsy 13 months after infection they showed no histopathological alterations. --five of six pigs infected with a trypanosoma brucei brucei strain from the ivory coast developed low parasitemia (up to about antilog 6.5 per ml of blood) which became progressively lower but was detectable up to one year after infection. on autopsy they showed interstitial myocarditis and meni ...19846464185
behaviour of a trypanosoma brucei brucei stock (stib 348c) in mice. 4. different course of primary parasitemia in trypanosome variants of different virulence.in three types of trypanosomes with low virulence, trypanosome numbers increased by a factor of 18-21 per day on average during prepatency and by a factor of 70-219 on average from the first to second day of patency. by contrast, a very virulent trypanosome variant showed an average increase of trypanosome numbers per day by 32 and 28 during prepatency and early patency, respectively. --in detailed studies, trypanosomes of low virulence exhibited a rapidly rising parasitemia in early patency whi ...19846464186
the in vitro trypanocidal activity of n-substituted p-benzoquinone imines: assessment of biochemical structure-activity relationships using the hansch approach.it has previously been found that naphthoquinones can potentiate the rate of hydrogen peroxide production by mitochondrial preparations of trypanosoma brucei brucei and that organisms treated with naphthoquinones are more susceptible to lysis, especially in the presence of compounds such as heme, which promote the homolytic cleavage of hydrogen peroxide. we have evaluated the lytic effect of various n-substituted p-benzoquinone imines both in vitro and in vivo and have attempted to correlate the ...19846470049
6 a-resolution x-ray structure of a variable surface glycoprotein from trypanosoma brucei.the variable surface glycoprotein (vsg) is the predominant component of the surface coat of the african trypanosome. the expression of antigenically distinct vsgs on minor populations during infection allows the parasite to escape the host immune response. purification of the protein is facilitated by the enzymatic release of a soluble form of vsg (svsg) which occurs on cell lysis. the soluble form is a dimer with an approximate molecular weight of 120,000-130,000. partial proteolysis of svsg re ...19846472475
alpha-helical coiled-coil structures of trypanosoma brucei variable surface glycoproteins.we have used electron microscopy to examine purified intact variable surface glycoproteins (vsgs) from clones derived from two distinct stocks of trypanosoma brucei. the vsg molecule from mitat 1.2 has a large elongated domain consistent with the shape of the dimeric n-terminal domain determined by x-ray analysis (see preceding paper), and a heretofore unseen short, thin fibrous tail presumed to be the c-terminal domain. electron microscopy on ditat 1.3, however, indicates a morphology quite dis ...19846472476
the role of the spleen in trypanosoma brucei brucei infection in dogs. 19846475405
pyruvate kinase: a carnitine-regulated site of atp production in trypanosoma brucei brucei.pyruvate kinase activity in trypanosoma brucei brucei is stimulated in the presence of l-carnitine and is inhibited by acetyl coa, atp or the atp-mg2+ complex. increased pyruvate kinase activity is associated with stimulation of atp synthesis in the presence of l-carnitine. there is evidence that carnitine stimulates pyruvate kinase activity indirectly by removing the inhibitory modulator acetyl coa as a result of the carnitine acetyl transferase (cat) also present in the trypanosomes.19846478790
messenger rna pieced together. 19846482959
[relations among 3 antigen repertoires of trypanosoma brucei brucei]. 19846486900
chromosome rearrangements in trypanosoma brucei.we have studied chromosome rearrangements in t. brucei using pulsed field gradient gel electrophoresis to separate chromosome-sized dna molecules. we detect size changes in a set of small chromosomes (200-700 kb) at a frequency of 10(-5) to 10(-6) per trypanosome division; this results in a radical difference in the size distribution of these chromosomes in different t. brucei isolates. several of these chromosome rearrangements can be related to a change in the expression of surface antigen gen ...19846488319
simultaneous purification of hexokinase, class-i fructose-bisphosphate aldolase, triosephosphate isomerase and phosphoglycerate kinase from trypanosoma brucei.a method is presented for the simultaneous purification of hexokinase, fructose-bisphosphate aldolase, triosephosphate isomerase and phosphoglycerate kinase, and the partial purification of glycerol-3-phosphate dehydrogenase (nad+), 6-phosphofructokinase, glucosephosphate isomerase, and glycerol kinase from trypanosoma brucei. as a first step, the glycosomes, microbody-like organelles of trypanosomatidae, containing almost exclusively enzymes involved in glucose and glycerol metabolism [opperdoe ...19846489338
light scattering and correlation measurement. 19846489595
the measurement of motility in micro-organisms and its biochemical significance. 19846489597
preliminary crystallographic studies of triosephosphate isomerase from the blood parasite trypanosoma brucei brucei.crystals of triosephosphate isomerase (ec 5.3.1.1) from trypanosoma brucei brucei have been grown. these crystals diffract to at least 2 a, even after 60 hours of exposure to x-rays. the space group is p212121, with cell dimensions a = 112.4 a, b = 97.8 a, c = 48.0 a. there is one dimer per asymmetric unit.19846492157
haemagglutinins and parasite agglutinins in haemolymph and gut of glossina.agglutinating activity was found in the haemolymph and in extracts of midgut and hindgut of glossina austeni against calf, guinea pig and chicken erythrocytes for the first time. trypanosoma brucei procyclic forms were also agglutinated by midgut and hindgut extracts, but not by haemolymph. the 3 fractions tested failed to react with erythrocytes of four other vertebrates and other trypanosomatids (leishmania hertigi and crithidia fasciculata) examined. the reciprocal titre of agglutinating acti ...19846495384
trypanosoma brucei-induced blockage of expulsion of echinostoma revolutum and of homologous e. revolutum resistance in mice.experiments were designed to study the effect of trypanosoma brucei on the expulsion of echinostoma revolutum and on the development and maintenance of homologous e. revolutum resistance in the mouse. t. brucei given 3, 2, and 1 wk before and 1 wk after infection with e. revolutum completely inhibited the expulsion of the e. revolutum worm burden for a period of at least 6 wk following infection, and t. brucei given 2 or 3 wk after infection with e. revolutum conferred a significant delay in the ...19846502358
enzyme variation in trypanosoma brucei spp. i. evidence for the sub-speciation of trypanosoma brucei gambiense.three groups of stocks of trypanosoma brucei ssp, defined by the criteria of host, human serum resistance and place of isolation as t. b. gambiense, t. b. brucei (nigeria) and t. b. brucei/rhodesiense (non-gambiense, uganda) were screened for electrophoretic variation at 20 enzyme loci. one enzyme (peptidase c) was found to differentiate all t. b. gambiense stocks from the other t. brucei stocks and, taken together with specific variants of 5 other enzymes, could be used to unambiguously define ...19846504561
delayed expulsion of hymenolepis diminuta in trypanosoma brucei infected mice.an experiment was conducted to study the effect of trypanosoma brucei on the expulsion of hymenolepis diminuta in the mouse. the study showed that t. brucei given 8 days before infection with h. diminuta resulted in a significant delay in the expulsion of the h. diminuta worm burden. this finding is suggested to be due to the immunosuppressive effect of the trypanosome.19846506844
serodiagnosis of trypanosomiasis in dromedary camels using a card agglutination test set (testryp catt). 19846508393
subcellular localization of photoreactive ethidium analogs in trypanosoma brucei by fluorescence microscopy.to identify the in vivo targets of the trypanocide, ethidium bromide, the fluorescent staining of t. brucei was examined for a series of ethidium analogs using fluorescence microscopy. determination of the biological targets for most drugs is limited by the reversible nature of their interactions. to overcome this limitation, photoaffinity (azido) analogs of ethidium, which are capable of covalent attachment with photoactivation, were used to identify the ethidium binding sites within the parasi ...19846512635
in vitro cultivation of trypanosoma (t.) brucei bloodstream forms using cell lines and sera from african wild bovidae. 19846512650
studies on the influence of non-steroidal anti-inflammatory drugs upon trypanosomiasis in goats and sheep.the non-steroidal anti-inflammatory drug (nsaid) flurbiprofen caused a rise in parasitaemia in goats infected with trypanosoma vivax, trypanosoma congolense and trypanosoma brucei. all trypanosome-infected goats treated with flurbiprofen showed many dividing trypanosomes. this also included the short-stumpy forms of t. brucei. in t. vivax-infected goats flurbiprofen treatment resulted in 100% mortality in the acute and chronic stages of the infection. the increase in parasitaemia of t. brucei in ...19846512919
characterization of spermidine synthase from trypanosoma brucei brucei.spermidine synthase from trypanosoma brucei brucei was characterized and found to be similar to spermidine synthase from other sources. the km for putrescine was found to be 0.2 mm and the km for decarboxylated s-adenosylmethionine 0.1 microm. the approximate molecular weight of the enzyme was 74 000 as determined by a combination of molecular sieve chromatography and sucrose density gradient centrifugation. spermidine synthase activity was markedly inhibited in vitro by dicyclohexylamine (50% i ...19846513985
the maxicircle of trypanosoma brucei kinetoplast dna encodes apocytochrome b.the region of the maxicircle of trypanosoma brucei kinetoplast dna which hybridizes at low stringency with the apocytochrome b gene of saccharomyces cerevisiae has been identified and cloned. the nucleotide sequence of a 1.7 kb segment of this region is reported. this segment contains a single long open reading from capable of coding for a 350 amino acid protein with substantial homology to apocytochromes b of other species. the trypanosome protein is considerably more distantly related to other ...19846513991
alpha-amanitin-insensitive transcription of variant surface glycoprotein genes provides further evidence for discontinuous transcription in trypanosomes.many, if not all, mrnas in t.brucei start with the same sequence of 35 nucleotides, separately encoded in clustered so-called mini-exon repeats. from these mini-exon repeats a 141-nt precursor rna with the 35-nt sequence at its 5' end is transcribed. indirect evidence suggests that this rna is linked in a second step to pre-mrna transcripts. we have studied the sensitivity of rna synthesis to alpha-amanitin in isolated trypanosome nuclei. transcription of several protein coding genes is almost c ...19846514580
the use of 2-substituted 5-nitroimidazoles in the treatment of chronic murine trypanosoma brucei infections with central nervous system involvement.chronic infections of trypanosoma brucei gvr 35/2 in mice, normally relapse after conventional chemotherapy because infective trypanosomes in the brain escape the action of the drug and are able to multiply and eventually re-establish a parasitaemia. however, if treatment consists of a single dose of 1 x 20 mg/kg suramin followed 3 or 4 days later by a 2-substituted 5-nitroimidazole, given intraperitoneally, either as a single dose or as a course of daily injections, relapses rarely occur and th ...19846524019
[parasitological, clinical and serological findings in dahomey cattle experimentally infected with trypanosoma congolense and t. brucei]. 19846525154
transport of alpha-aminoisobutyrate into trypanosoma brucei brucei.the uptake of alpha-aminoisobutyrate (aib) by washed cell suspensions of bloodstream forms of trypanosoma brucei brucei has been shown to be an energy-dependent process. no metabolism of aib was detected under conditions leading to a 100-fold accumulation of aib within the organism. kinetic studies revealed that aib uptake involved two components; that operating at low substrate concentrations had an apparent km of 4.6 mm. experiments with ionophores such as gramicidin and carbonylcyanide m-chlo ...19846527126
a ph-stat method for studying glycolysis in trypanosoma brucei. 19846527180
[characterization of the vector capacity of glossinia morsitans morsitans (diptera: glossinidae) towards trypanosoma brucei brucei eatro 1125 (antar 1)]. 19846529273
detection of circulating trypanosomal antigens by enzyme immunoassay.antisera raised against trypanosoma evansi and t. congolense were used in a double antibody sandwich enzyme immunosorbent assay (elisa) to detect trypanosomal antigens in sera from experimentally infected rabbits and goats. assays quantitated using reference antigen preparations and the homologous antisera showed that antigens could be detected at protein concentrations of 1.5 microgram ml-1. the antisera also cross-reacted with soluble antigens prepared from t. brucei and t. vivax at similar pr ...19846532328
a longitudinal study of the susceptibility to normal human serum of a trypanosoma brucei rhodesiense clone non-cyclically passaged in rats. 19846535712
[antigenic variants detected after cyclic transmission of a clone of trypanosoma brucei brucei in trypanosensitive and resistant cattle]. 19846544965
many trypanosome messenger rnas share a common 5' terminal sequence.the mrnas for different variant surface antigens of trypanosoma brucei start with the same 35 nucleotides. this sequence is encoded by a separate mini-exon, located in a 1.35-kb repetitive element. we have reported that trypanosomes contain many transcripts that hybridize to mini-exon probes, even if they do not make the surface antigens. we show here that these transcripts have the mini-exon sequence at their 5' end; they do not contain other sequences from the mini-exon repeat element and are ...19846547230
antitumor phthalanilides active in acute and chronic trypanosoma brucei brucei murine infections.a series of phthalanilides and related compounds were tested on a short-term, fulminating, mouse infection of trypanosoma brucei brucei (eatro 110 isolate). the most effective compound was [4,4'-bis (4-methylimidazolin-2-yl)-terephthalanilide] which had a cure rate of 75% at 0.1 mg/kg body weight and 100% at 0.5 mg/kg when administered as three single daily intraperitoneal injections starting 24 hours post-infection. several related phthalanilides and similarly substituted ureas showed definite ...19846548337
localization of the initial steps in alkoxyphospholipid biosynthesis in glycosomes (microbodies) of trypanosoma brucei.cell fractionation of trypanosoma brucei cultured procyclic stages showed that the key enzyme of glycerol-ether lipid synthesis, dihydroxyacetone-phosphate acyltransferase (ec 2.3.1.42) was exclusively associated with the microbody fraction. these organelles contained in addition 1-acyl glycerol-3-phosphate: nadp+ oxidoreductase (ec 1.1.1.101) and acyl-coa reductase and were capable of utilizing dhap, but not g-3-p, as substrate for lysophosphatidic acid formation. it is concluded that in t. bru ...19846562019
trypanosome variant-specific glycoproteins: a polygene protein family with multiple folding patterns?infection with the african trypanosomes gives rise to relapsing waves of parasitemia in the host. a predominant population of trypanosomes is present in each wave, and such predominant populations are usually serologically distinct from each other. trypanosomes are covered by an extramembranous, highly antigenic, variant-specific glycoprotein coat that is 15 nm thick. the primary structure of a large portion of the glycoprotein molecule is different in the predominant trypanosome populations of ...19846583708
the intracellular pathway and assembly of newly formed variable surface glycoprotein of trypanosoma brucei.pulse-chase experiments using l-[35s]methionine suggest that trypanosoma brucei mitat 1.2 variable surface glycoprotein (vsg) synthesized in the rough endoplasmic reticulum, a process that takes 6-8 min, is shuttled to the golgi complex 8 min later. labeling of ultrathin frozen sections with affinity-purified anti-cross-reacting determinant (crd) igg followed by protein a-colloidal gold shows that the crd is localized in the trans-golgi region. cis-golgi is not labeled. vsg, when solubilized by ...19846595657
a quantitative ultrastructural study on the transformation of trypanosoma brucei metacyclic to bloodstream forms in vitro.the transformation of metacyclic to bloodstream forms of trypanosoma brucei brucei was studied in vitro using light and electron microscopy. the ultrastructural composition was investigated with stereological methods and the mean cell volume determined in a coulter channelyzer. the mitochondrion showed the most significant changes during transformation with a reduction in volume as well as in the membrane areas. the glycosomes remained unchanged whereas the lipid inclusions increased over the 24 ...19846147983
failure of trypanosomal membrane antigens to induce protection against tsetse-transmitted trypanosoma vivax or t. brucei in goats and rabbits.a purified protein, relative molecular weight 83 kilodalton (kd), and plasma membranes from trypanosoma brucei were tested as potential vaccines against tsetse-transmitted t. vivax and t. brucei in goats and rabbits. the 83 kd protein was found in lysates of all clones of t. brucei examined, as well as in lysates of t. vivax, t. congolense and t. rhodesiense. rabbits and goats were immunized with various amounts of antigen in freund's complete adjuvant and boosted twice with antigen in freund's ...19846150617
cerebral trypanosomiasis in cattle with mixed trypanosoma congolense and t. brucei brucei infections.six boran steers were infected simultaneously with trypanosoma congolense and t. brucei brucei while another group of 3 was inoculated with t. b. brucei one year after infection with t. congolense. three further steers were infected with t. b. brucei alone. whereas, the six animals which received simultaneous infections developed clinical signs of cerebral trypanosomiasis as evidenced by depression, ataxia and occasional circling, those infected with t. b. brucei alone did not. at necropsy, 4 ou ...19846150618
the contribution of chromosomal translocations to antigenic variation in trypanosoma brucei.genomic rearrangements influencing gene expression occur throughout nature. several of these rearrangements disrupt normal gene expression, as exemplified by the genetic alterations caused by the mobile genetic elements of maize or drosophila (see shapiro 1983). other rearrangements are part of the normal developmental programme of an organism. an understanding of the control of genomic rearrangements and their effects on gene expression should contribute to our insight into the mechanism of gen ...19846151678
structure of the variant glycoproteins and surface coat of trypanosoma brucei.the pathogenic african trypanosomes have a unique mechanism for antigenic variation. each cell is covered by a surface coat consisting of about seven million essentially identical glycoprotein molecules drawn from a large repertoire of variants, each encoded by an individual gene. amino acid sequence variation extends throughout the molecule but reduces from the amino terminus to the carboxy terminus, where certain features, especially the grouping of cysteine residues, are quite conserved. the ...19846151686
analysis by flow cytometry of dna synthesis during the life cycle of african trypanosomes.dna content, at different stages in the life cycle of the hemoprotozoan parasite trypanosoma brucei, has been analysed with a fluorescence activated cell sorter. it was observed that the long slender bloodstream form stage and procyclic culture forms (analogous to the tsetse fly midgut stage) are dividing cell populations with cells in g1, s, g2 and mitosis. short stumpy bloodstream form and metacyclic fly salivary gland form populations are composed of non-dividing parasites stabilized in g1 or ...19846152113
the acquisition of human serum resistance by a trypanosoma brucei brucei clone during non-cyclical passage and repeated exposure to normal human serum in vivo. 19846152583
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
antigenic variation in trypanosoma brucei analyzed by electrophoretic separation of chromosome-sized dna molecules.pulsed field gradient gel electrophoresis fractionates chromosome-sized dna molecules from t. brucei. about 60% of the dna remains in or close to the gel slot (large dna). there are about three chromosomes of approximately 2 mb, at least six chromosomes of 200-700 kb, and roughly a hundred mini-chromosomes of 50-150 kb. the basic copy genes for vsgs 118 and 221 reside in large dna. their activation by duplicative transposition leads to the appearance of an additional copy in the 2 mb dna, showin ...19846202420
antigenic variation during the developmental cycle of trypanosoma brucei.during the complex life cycle of trypanosoma brucei, changes in the exposed surface antigens occur in both the mammalian host and the insect vector (glossina spp.). these antigenic changes are associated with alterations of the variant surface glycoprotein (vsg) composition or with the loss of the vsg. in the bloodstream of the mammalian host, trypanosomes successfully evade destruction by the host's immune response by continuously expressing alternative vsgs, at low frequency, which are not des ...19846204043
comparison of the genes coding for the common 5' terminal sequence of messenger rnas in three trypanosome species.messenger rnas of trypanosoma brucei share a common 5' terminal sequence of 35 nucleotides, encoded by a mini-exon located in 1.35-kb tandemly linked repeats. we show here that sequences, almost identical to the mini-exon of t. brucei, are present in mrnas from members of two other kinetoplastid subgenera: trypanosoma vivax and trypanosoma cruzi. as in t. brucei, these mini-exons are encoded by small tandemly linked repeat elements. we have determined and compared the nucleotide sequences of the ...19846204273
expression of antigenic regions of a trypanosome variable surface glycoprotein in e. coli using bal-31 nuclease digestion.we have used the expression of a trypanosome variable surface glycoprotein (vsg) in e. coli to produce vsg serotype-specific antisera which have none of the cross-reacting specificities characteristic of antisera prepared against purified vsgs. this was accomplished by treating restriction fragments of vsg cdnas with bal-31 nuclease to facilitate expression of their open reading frames in the e. coli expression vector, pmr100 (4). the resultant vsg-beta-galactosidase fusion proteins possess vari ...19846204274
cytotoxicity of monoclonal antibodies to trypanosoma brucei.monoclonal antibodies (mcabs) were raised against metacyclic variable antigen types (m-vats) of the antar 1 and etar 1 serodemes of trypanosoma brucei. two dominant m-vats, one from each serodeme, were labelled by two of the mcabs using the indirect immunofluorescence technique. these mcabs were of the igm class, and labelled exposed epitopes on living trypanosomes. they showed lytic activity in vitro towards their respective homologous vat trypanosomes, both in the presence and absence of compl ...19846207646
identification of a telomeric dna sequence in trypanosoma brucei.a simple repetitive dna sequence in the nuclear genome of trypanosoma brucei, consisting of tandem repeats of the hexanucleotide 5' ccctaa 3', was identified as being telomeric by several criteria. this sequence was specifically labeled with t. brucei genomic dna as the template for in vitro nick translation by dna polymerase i, and was present in bal 31 nuclease sensitive, genomic restriction fragments of the large sizes expected in this organism for at least some telomeric regions. the same re ...19846319025
structure of the growing telomeres of trypanosomes.we have developed a method for the molecular cloning of dna adjacent to chromosome ends (telomeres). a recombinant dna clone obtained from the telomeres of the protozoan trypanosoma brucei contains large stretches of the repeat (ccctaa)n. this repeat is flanked by a larger subtelomeric repeat (29 bp in one case). these repeats account for the presence of large dna stretches not cut by restriction enzymes downstream of telomeric vsg genes. all telomeres analyzed thus far (more than 30) grow by ap ...19846319026
subcellular distribution and partial characterization of the cyclic amp-binding proteins of trypanosoma brucei.we assayed the cyclic amp-binding activity of trypanosoma brucei by two well established methods, such as the one of gilman (proc. natl. acad. sci. u.s.a. 67, 305-312, 1970) and ueland & doskeland (biochem. j., 157, 117-126, 1976). the results indicate that the former technique underestimated the total amount of cyclic amp bound by t. brucei homogenates by up to 7.5 fold. similar results were obtained with other trypanosomatidae such as leishmania tropica, and crithidia luciliae. the bulk of the ...19846321981
variant antigen genes of trypanosoma brucei: genomic alteration of a spliced leader orphon and retention of expression-linked copies during differentiation.variant surface glycoprotein (vsg) gene expression in trypanosoma brucei involves not only the sequential activation of individual vsg genes during mammalian bloodstream stage antigenic variation but also the regulation of gene expression during cyclic transmission through alternate mammalian and insect hosts. in the bloodstream stage, transcriptional activation of many vsg genes is correlated with the appearance of an additional copy of the gene in a novel genomic location, the expression-linke ...19846322164
distinction of african trypanosome species using nucleic acid hybridization.we have performed restriction endonuclease digestion of nuclear dnas, combined with gel electrophoresis and molecular hybridization to characterize different trypanosoma brucei brucei stocks and to identify trypanosome species. cloned dna complementary to the messenger rnas (mrnas) for different variable surface glycoproteins (vsgs) of t. b. brucei stock lump 227 was used to examine differences in genomic dnas from t. b. brucei stocks and from various other trypanosome species. these cdna reagen ...19846324058
indomethacin promotes differentiation of trypanosoma brucei.the treatment of mice with indomethacin lowered trypanosoma brucei parasitemia 1 to 2 log10 because it quickly promoted the differentiation of rapidly dividing long, slender trypanosomes into short, stumpy forms that do not divide in the mammal but do develop a functional mitochondrion and the ability to infect the tsetse. since natural resistance correlates with the rate of differentiation, this observation may provide important information about factors that control the severity of trypanosomi ...19846690416
trypanocidal 1,3-arylene diketone bis(guanylhydrazone)s. structure-activity relationships among substituted and heterocyclic analogues.based on the antitrypanosomal activity of 1,3-diacetylbenzene bis(guanylhydrazone) (4) and 2,6-diacetylpyridine bis(guanylhydrazone) (17), a number of substituted and heterocyclic 1,3-arylene diketone bis(guanylhydrazone)s were prepared and tested against trypanosoma brucei infections in mice. a wide range of ed50 values was observed among 5-substituted derivatives of 4. the 5-amino analogue 5 and 5-acetamido analogue 6 were about twice as active as 4. 1,3,5-triacetylbenzene tris(guanylhydrazone ...19846690682
two modes of activation of a single surface antigen gene of trypanosoma brucei.several genes for variant antigens in trypanosomes are activated by duplicative translocation to a telomeric expression site. a second--nonduplicative--mode of activation is restricted to telomeric antigen genes. we show here that the single telomeric gene for antigen 221 can be activated in both ways. we also show that gene 221 is split and that the 5' 35 nucleotide sequence, common to all surface antigen mrnas, is not encoded within 8.5 kb upstream of the 221 coding region. no major rearrangem ...19846692467
anti-trypanosome specific immune responses in bovids of differing susceptibility to african trypanosomiasis.a clone of trypanosoma brucei brucei (ditat 1.1) was injected into 32 bovids of various breeds, 11 animals being kept as controls. five animals, simmental-ndama f1 crosses, were extremely sensitive. they showed overt symptoms and one died on day 18 of infection despite treatment with a trypanocidal drug. seven other animals became ill but recovered progressively and cleared the infection. twenty animals, of breeds generally considered to be trypanosensitive as well as ones from trypanotolerant b ...19846693134
resistance of cattle to tsetse-transmitted challenge with trypanosoma brucei or trypanosoma congolense after spontaneous recovery from syringe-passaged infections.groups of cattle were inoculated intravenously with cloned populations of bloodstream forms of trypanosoma brucei or trypanosoma congolense. all five steers infected with t. brucei iltat 2.1 and six of the eight steers infected with t. congolense il 13-e14 became aparasitemic within 16 and 32 weeks postinfection, respectively. examination of sera from animals infected with t. brucei by indirect immunofluorescence and neutralization assays revealed the presence of antibodies against all the metac ...19846693173
myristylation of the membrane form of a trypanosoma brucei variant surface glycoprotein.a variant surface glycoprotein (vsg) of the parasitic protozoan trypanosoma brucei was purified following the direct solubilization of trypanosomes in a boiling detergent solution. this material behaved as the amphiphilic membrane form of the glycoprotein previously described (cardoso de almeida, m. l., and turner, m. j. (1983) nature (lond.) 302, 349-352). analysis of this material showed that it contained ester-linked tetradecanoic (myristic) acid. after biosynthetic labeling of trypanosomes w ...19846699005
partial purification and characterization of microtubular protein from trypanosoma brucei.the tubulin proteins of the parasitic hemoflagellate trypanosoma brucei brucei were purified and characterized. cytoskeletal microtubules of trypanosomes do not disrupt under conditions used to solubilize brain tubulins. trypanosomal tubulins, solubilized by extensive sonication, were partially purified from the crude cell extracts by taxol-mediated polymerization. taxolinduced microtubules were identified by electron microscopy and analyzed biochemically. they consist predominantly of two prote ...19846707021
evolution of a trypanosome surface antigen gene repertoire linked to non-duplicative gene activation.african trypanosomes activate, one at a time, a large set of genes coding for different variant-specific surface antigens (vsas). these genes have been classed into two groups. in the first group a permanently silent basic gene copy is duplicated and the expression-linked copy (elc) transposed to an expression site located at a chromosome end. the process is a gene conversion which changes a variable stretch of the preceding elc. genes belonging to the second group do not give rise to an additio ...19846709043
parasite development and host responses during the establishment of trypanosoma brucei infection transmitted by tsetse fly.following inoculation of trypanosoma brucei into large mammals by the tsetse fly a local skin reaction, the 'chancre', develops due to trypanosome proliferation. we have cannulated the afferent and efferent lymphatics of the draining lymph node in goats and examined the onset of a cellular reaction, the emigration of the parasite from the chancre and the development of both antigenic variation and the specific immune response. the chancre first became detectable by day 3 post-infection, peaked b ...19846709396
isolation of phospholipase a1 from trypanosoma brucei.phospholipase a1 from trypanosoma brucei brucei has been purified 380-fold by column chromatography on phosphatidylcholine-sepharose affinity columns followed by deae-cellulose anion-exchange chromatography and sephacryl s-200 molecular exclusion chromatography. octyl-agarose hydrophobic column chromatography can be substituted for the pc-sepharose column. the molecular weight of trypanosomal plase a1 was found to be 26,000 by sds-polyacrylamide gel electrophoresis.19846710597
ribosomal rna genes of trypanosoma brucei: mapping the regions specifying the six small ribosomal rnas.there are six small ribosomal rnas in trypanosome ribosomes. srna3 and srna5 of trypanosoma brucei brucei have been partially sequenced. sequence homologies indicate that srna3 is 5.8s rna and srna5 is 5s rna of t. b. brucei. the regions specifying these two, and the remaining four small rnas, have been identified within clones of rrna genes and in the genome. five of the small rnas, 1, 2, 3, 4 and 6, hybridise exclusively within the major rrna gene repeat. a map of the regions specifying these ...19846714673
purification, morphometric analysis, and characterization of the glycosomes (microbodies) of the protozoan hemoflagellate trypanosoma brucei.trypanosoma brucei glycosomes (microbodies containing nine enzymes involved in glycolysis) have been purified to near homogeneity from bloodstream-form trypomastigotes for the purpose of morphologic and biochemical analysis. differential centrifugation followed by two isopycnic centrifugations in an isotonic percoll and in a sucrose gradient, respectively, resulted in 12- to 13-fold purified glycosomes with an overall yield of 31%. these glycosomes appeared to be highly pure and contained less t ...19846715405
[from cancer cell to trypanosoma and back]. 19846717651
release and purification of trypanosoma brucei variant surface glycoprotein.conditions affecting the solubilization of variant surface glycoprotein (vsg) from trypanosoma brucei have been investigated. the results obtained form the basis for a convenient and efficient method for vsg purification. vsg release from the cell surface was temperature-dependent, following osmotic lysis at 0 degree c, and was inhibited by low concentrations of zn2+ but not by tosyl-lysine chloromethyl-ketone (tlck), phenylmethylsulfonylfluoride (pmsf), or iodoacetamide. these and other results ...19846725422
pathogenesis of trypanosoma brucei infection in deer mice (peromyscus maniculatus). ultrastructural pathology of the spleen, liver, heart, and kidney.trypanosoma brucei eatro 110 infection of the deer mice (peromyscus maniculatus) produced moderate to marked lesions in the spleen, liver, heart, and kidney seven to ten weeks after infection. splenic lesions consisted of marked splenomegaly, with infected spleens weighing 25.9 times control spleens. transmission electron microscopy of the sinuses and billroth's cords of the splenic red pulp demonstrated an increased cellularity with greater contact between cells due partly to proliferation of m ...19846730206
pathogenesis of trypanosoma brucei infection in deer mice (peromyscus maniculatus). light and electron microscopic study of testicular lesions.the results of light and electron microscopic studies demonstrated that trypanosoma brucei infection produced marked testicular degeneration in deer mice (peromyscus maniculatus) with highly significant (p less than 0.001) decreases in testicular weight, seminiferous tubular diameter, and epithelial thickness. lesions in seminiferous tubules consisted of necrosis of spermatids, spermatocytes, and sometimes the spermatogonia. sertoli's cells had marked vacuolation and accumulation of phagocytic m ...19846730207
response of the rat's hepatic drug-metabolizing enzyme system to chemotherapy of trypanosoma b. brucei infections with berenil and suramin.berenil (4,4-diamidinodiazoaminobenzene-diacetamide acetate) or suramin [sodium salt of 8-(3-benzamido-4-methylbenzamido)-naphthalene-1,3,5-trisulfonic acid] treatment of rats infected with trypanosoma b. brucei enhanced hepatic microsomal aniline hydroxylase and p-aminopyrine n-demethylase activities. while suramin inhibited significantly the activities of cytoplasmic glutamate dehydrogenase and lactate dehydrogenase, berenil had no effect. the kinetic profiles of these enzymes consistently sho ...19846734575
the role of duplication in the expression of a variable surface glycoprotein gene of trypanosoma brucei.the variable surface glycoprotein (vsg) genes of trypanosoma brucei have been classified into two groups depending upon whether or not duplication of the genes is observed when they are expressed. we report here the observation of duplication apparently linked to expression of the iltat 1.3 gene in the etar 1 trypanosome stock. in the iltar 1 stock, expression of the iltat 1.3 vsg did not involve a new duplication, but instead activation of a preexisting gene copy that had been apparently genera ...19846736139
purification and properties of the membrane form of variant surface glycoproteins (vsgs) from trypanosoma brucei.variant surface glycoproteins (vsg) of trypanosoma brucei are released in a water soluble form on impairment of membrane integrity. we have previously shown that this release is the result of an enzyme-mediated event which converts the hydrophobic membrane form vsg into the hydrophilic water-soluble form. we now present further details of the methods by which membrane form vsg ( mfvsg ) may be isolated, uncontaminated by water-soluble vsg ( svsg ). the sensitivity to different metal ions of the ...19846737318
identification of an acridine photoaffinity probe for trypanocidal action.twenty-four acridine derivatives were screened for trypanocidal activity in trypanosoma brucei in order to determine which structural features of the acridine molecule confer maximal antiparasitic activity. the synthesis of several new azidoacridine derivatives are also reported as well as an assessment of their value as possible photoaffinity probes for the study of acridine trypanocidal action. the most effective and selective acridine trypanocides, with and without irradiation, were the 3-ami ...19846737429
trypanosoma brucei: biochemical and morphological studies of cytotoxicity caused by normal human serum.the biochemical and morphological events which accompany lysis of trypanosoma brucei by normal human serum have been described. the prelytic events include loss of infectivity and rapid cation shifts across the cell membrane. this is followed by cell swelling, fraying of the surface coat of the cell, loss of intracellular organelles, and eventually cell lysis. the data presented are consistent with a colloid osmotic mechanism of lysis induced by irreversible acute damage to the normal permeabili ...19846745390
glycosyltransferase activities in golgi complex and endoplasmic reticulum fractions isolated from african trypanosomes.highly enriched golgi complex and endoplasmic reticulum fractions were isolated from total microsomes obtained from trypanosoma brucei, trypanosoma congolense, and trypanosoma vivax, and tested for glycosyltransferase activity. purity of the fractions was assessed by electron microscopy as well as by biochemical analysis. the relative distribution of all the glycosyltransferases was remarkably similar for the three species of african trypanosomes studied. the golgi complex fraction contained mos ...19846746739
genetics of resistance to the african trypanosomes. iii. variant-specific antibody responses of h-2-compatible resistant and susceptible mice.genetically based differences in variant-specific immunity to the african trypanosomes were examined. h-2-compatible inbred mouse strains that differed in relative resistance were infected with trypanosoma rhodesiense clone loutat 1. antibody responses to exposed epitopes of the loutat 1 variant-specific surface glycoprotein (vsg) were measured. relatively resistant b10.br mice (h-2k) made predictable igm antibody responses to the vsg of loutat 1 which were associated with clearance of the louta ...19846747297
a comparison of the glycosomes (microbodies) isolated from trypanosoma brucei bloodstream form and cultured procyclic trypomastigotes.highly purified glycosomes were isolated from trypanosoma brucei bloodstream forms and cultured procyclic trypomastigotes. a comparison of the specific activities of glycosomal enzymes revealed that glycosomes from insect stages had decreased levels of hexokinase, phosphoglucose isomerase, phospho-fructokinase, fructose-bisphosphate aldolase, glyceraldehyde-phosphate dehydrogenase and phosphoglycerate kinase, but contained increased levels of adenylate kinase, malate dehydrogenase and phosphoeno ...19846749187
threonine uptake in trypanosoma brucei.threonine uptake by the parasitic protozoan trypanosoma brucei has been assessed using an oil-phase separation technique for measuring rapid amino acid fluxes. it was shown that the storage conditions for the organism were critical for the production of reproducible data. using this method it has been shown that threonine uptake occurs rapidly, being linear for less than 30 s at 37 degrees c in contrast with previous reported results. kinetic analysis of threonine uptake at 25 degrees c and at p ...19846431284
new drug combination for experimental late-stage african trypanosomiasis: dl-alpha-difluoromethylornithine (dfmo) with suramin.using a previously described mouse model of late-stage african trypanosomiasis (i.e., involvement of the central nervous system), we demonstrate that a combination of dl-alpha-difluoromethylornithine (dfmo) and suramin is curative. in the curative protocol, dfmo is given as a 2% solution in the drinking water for 14 days and suramin is administered as a single dose (20 mg/kg intravenously) on day 1 of dfmo administration. since: 1) dfmo has very low toxicity, 2) suramin is one of the least toxic ...19846439061
the istar 1 serodeme of trypanosoma brucei: development of a new serodeme.an extensive serodeme of sequentially-isolated antigenic variants of african trypanosomes has been produced from both syringe-passaged and cyclically-transmitted trypanosoma brucei of the istar 1 clone derived from eatro 164. the majority of the antigenic variants were isolated from chronically-infected deer mice (peromyscus leucopus). the pattern of parasitemias during the course of infections initiated with syringe-passaged trypanosomes differed from those initiated with cyclically-transmitted ...19846439844
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
comparison of the levels of autofluorescence caused by fixatives in fluorescence assay on trypanosomes. 19846441838
activation of genes for variant surface glycoproteins in trypanosomes. 19846400772
diverse patterns of expression of the cytochrome c oxidase subunit i gene and unassigned reading frames 4 and 5 during the life cycle of trypanosoma brucei.transcription of a maxicircle segment from trypanosoma brucei 164 that contains nucleotide (nt) sequences corresponding to cytochrome c oxidase subunit i (coi) and unassigned reading frames (urfs) 4 and 5 of other mitochondrial systems was investigated. two major transcripts that differ in size by ca. 200 nt map to each of the coi and urf4 genes, while a single major transcript maps to urf5. in total rna, the larger coi transcript is more abundant in procyclic forms (pfs) than in bloodstream for ...19852427925
the role of rna priming in viral and trypanosomal mrna synthesis. 19852408758
further characterization of the extremely small mitochondrial ribosomal rnas from trypanosomes: a detailed comparison of the 9s and 12s rnas from crithidia fasciculata and trypanosoma brucei with rrnas from other organisms.we have determined the nucleotide sequence of a maxi-circle segment from the insect trypanosome crithidia fasciculata mitochondrial dna, on which the genes for the major maxicircle transcripts of 9s and 12s are localized. the 5'-terminal sequences of these rnas were determined by wandering spot analysis. the map coordinates of the 9s and 12s rnas from trypanosoma brucei were adjusted with respect to a previous report with the aid of primer extension analysis with reverse transcriptase. this appr ...19852409531
mature mrnas of trypanosoma brucei possess a 5' cap acquired by discontinuous rna synthesis.mature mrnas of trypanosoma brucei have a common 5' terminal sequence of 35 nucleotides. this is acquired by an unknown mechanism from the 5' end of a separately transcribed precursor rna of about 140 nt called the mini-exon-derived rna or medrna. we have investigated the nature of the 5' ends of mature mrnas and of the medrna by chemical decapping and enzymic recapping. we infer that a 5' cap is present on both of these rnas and conclude that the mini-exon-derived rna donates its 5' cap along w ...19852409534
apocytochrome b and other mitochondrial dna sequences are differentially expressed during the life cycle of trypanosoma brucei.cytochromes and krebs cycle enzymes are not detected in bloodstream forms of trypanosoma brucei but are present in procyclic forms. we have analyzed transcription of mitochondrial sequences which contain the apocytochrome b gene and several other open reading frames (orfs). multiple transcripts map to individual dna sequences located on both dna strands. larger low abundance transcripts map to multiple orfs and may be precursor rnas. small abundant transcripts map to g + c rich sequences that do ...19852409537
the biochemistry of the surface antigens of the african trypanosomes. 19852411331
Refresh
firstprev
12345678910...
nextlast
Displaying items 901 - 1000 of 5727