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phenotypic segregation of aedes aegypti for immune antibacterial activity and resistance to filariae.we report the phenotypic selection of two lines of aedes aegypti, from a filariae susceptible parental stock (refm). this selection was based upon the level of inducible anti-gram negative escherichia coli activity within the haemolymph following e. coli infection. these lines, denoted 'high' and 'low', demonstrated significant differences in anti-e. coli responses throughout. however no difference was observed in the anti-gram positive micrococcus luteus response following e. coli challenge. f4 ...19968858873
discrete transcripts encode multiple chitinase isoforms in brugian microfilariae.the blood-borne microfilariae of the brugian nematodes produce multiple isoforms of chitinase, whose expression is coincident with the onset of microfilarial infectivity for mosquitoes. a single cdna sequence was previously obtained by screening a brugia malayi microfilarial cdna library, yet two chitinase isozymes are readily distinguished in this species. in this paper, we present evidence for the existence of multiple transcripts encoding brugian microfilarial chitinases. using primers based ...19968892292
in vivo effect of a natural aedes aegypti defensin on brugia pahangi development. 19968994145
suppression of mitogen-induced il-2r alpha expression in pbl by serum from microfilaraemic rats chronically infected with brugia pahangi.to study immunological responses in filarial infections, interleukin-2 receptor alpha (il-2r alpha) expression in the peripheral blood lymphocytes (pbl) of lewis rats infected with brugia pahangi was observed by flow cytometry. during infection, no increase in il-2r alpha was observed in either microfilaraemic or amicrofilaraemic rats. the pbl of rats were stimulated with phytohaemagglutinin (pha) and the frequency of il-2r alpha-positivity was examined. after microfilariae appeared, the increas ...19979011075
expression of the microfilarial sheath protein 2 (shp2) of the filarial parasites litomosoides sigmodontis and brugia malayi.the microfilarial sheaths of the filarial parasites brugia malayi, brugia pahangi, and litomosoides sigmodontis consist of several parasite proteins, probably ranging between 7 and 10. the gene encoding sheath protein 2 (shp2), which is the object of this study, is transcribed in embryos and in the uterine epithelium; at least in b. malayi, it is translated in both tissues. apparently, shp2 is synthesized as a monomer, exported by the respective cells, and integrated into the microfilarial sheat ...19979085921
down-regulation of murine susceptibility to cerebral malaria by inoculation with third-stage larvae of the filarial nematode brugia pahangi.in areas where malaria is endemic, helminthic infections, caused by intestinal or filarial parasites, commonly coexist with malaria in the same individual. this study investigates the course of plasmodium berghei malaria infection in cba/j mice inoculated with irradiated attenuated 3rd-stage larvae (l3) of brugia pahangi. peripheral eosinophil counts, serum ige levels and cytokine production revealed that the filarial antigen induced t-helper type 2 (th2) cell predominance in these mice, which p ...19979107020
variation in the nature of attachment of phosphorylcholine to excretory-secretory products of adult brugia pahangi.the mechanism of linkage of phosphorylcholine (pc) to excretory-secretory products (es) of adult brugia pahangi has been investigated. biosynthetic radio-isotope labelling of es with [3h]choline followed by sds-page/fluorography revealed a smear of molecular weight approximately 40-100 kda which loses its radiolabel following exposure to n-glycosidase f, but not mild alkali. pc is thus attached to this smear of molecules via n-type glycans, a mechanism of linkage previously observed with respect ...19979139257
brugia pahangi in cats: the passive transfer of anti-microfilarial immunity from immune to non-immune cats.serum from cats (felis catus) that were repeatedly infected with brugia pahangi and had become amicrofilaraemic (mf-ve) was injected intravenously into microfilaraemic (mf+ve) cats. if more than 1 microliter of immune serum per 1000 mf was injected, microfilarial counts fell dramatically within minutes and, in some cats, mf completely disappeared. in most cases mf reappeared 21-44 days later. however, in two experiments mf never reappeared and circulating antigen (indicative of the presence of l ...19969223160
differentially expressed, abundant trans-spliced cdnas from larval brugia malayi.isolation and cloning of abundant reverse transcriptase-polymerase chain reaction (rt-pcr) products from the filarial nematode brugia malayi using the conserved nematode spliced leader sequence and poly a as amplification targets has allowed us to identify abundant, stage specific transcripts from infective and post-infective larvae. the predicted protein products of the most prominent full-length transcripts from mosquito-derived l3 parasites are: (i) bm-alt-1, a homologue of a dirofilaria immi ...19979233676
adoptive transfer of granulomatous inflammation to brugia antigens in jirds.brugia pahangi infections of jirds (meriones unguiculatus) produce a granulomatous inflammatory response within the lymphatic vessels. granulomas that form around beads coated with soluble adult antigens embolized in the lungs have been used to measure this response. similar lesions were observed in naive jirds receiving lymph node cells and splenocytes from animals with acute infections. this was not the case with cells from chronically infected jirds that were hyporesponsive to implanted antig ...19979267402
a cytidine deaminase expressed in the post-infective l3 stage of the filarial nematode, brugia pahangi, has a novel rna-binding activity.a number of genes have been identified that are highly expressed in the post-infective l3 stage of the filarial parasite, brugia pahangi. amongst these was a cdna with homology to the cytidine deaminase (cdd) gene family. phylogenetic analysis of the various cytosine nucleoside deaminases suggest that brugia pahangi cdd evolved with significant divergence from the rna editing family. in order to characterize its function, we have expressed brugia pahangi cdd in bacteria as a chimera with maltose ...19979274872
brugia pahangi: differential induction and regulation of jird inflammatory responses by life-cycle stages.it has been hypothesized that different life-cycle stages of filarial nematodes induce different host responses. this concept was examined in the brugia pahangi-jird model of lymphatic filariasis by measuring the kinetics of inflammatory responses to parasite antigens following intraperitoneal inoculation of different life-cycle stages. for this purpose, viable female or male worms, l3, l4, or microfilarial stage, were used. dead worms served as controls. worm and microfilarial burdens, pulmonar ...19979287954
the use of inhibitors of n-linked glycosylation and oligosaccharide processing to produce monoclonal antibodies against non-phosphorylcholine epitopes of brugia pahangi excretory-secretory products.adult brugia pahangi were cultured with [3h]-choline in both the absence and the presence of either tunicamycin or 1-deoxymannojirimycin (dmm), inhibitors of n-linked glycosylation and n-linked oligosaccharide processing, respectively. excretory-secretory products (es) were recovered from the spent medium and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/fluorography. both inhibitors were found to prevent radiolabeling of es, a result consistent with blockage of the addit ...19979342749
a member of the tgf-beta receptor gene family in the parasitic nematode brugia pahangi.the full length cdna sequence of a type i transforming growth factor-beta (tgf-beta) receptor has been isolated from the filarial parasitic nematode brugia pahangi. this new gene, designated bp-trk-1, encodes a predicted 645 amino acid sequence with an n-terminal hydrophobic stretch which may act as a signal peptide. the extracellular portion (residues 15-187) is cysteine-rich and has three potential n-glycosylation sites. at positions 250-255 the protein contains the glycine-serine rich motif c ...19979358045
plasma levels of diethylcarbamazine and their effects on implanted microfilariae of brugia pahangi in rats.plasma level of diethylcarbamazine (dec) was measured by using gas chromatography and was compared to the changes of microfilaremia after an intraperitoneal injection with 200 mg/kg of dec in rats. the microfilaremia was induced artificially by an intravenous implantation with 2 x 10(5) brugia pahangi microfilariae (mf) 1 day before dec treatment. the rats treated with dec showed a rapid and significant decrease in mf number in the circulation within 30 min, continued for 4 hr, and then increase ...19979362054
effect of gamma radiation on brugia l3 development in vivo and the kinetics of granulomatous inflammation induced by these parasites.previous studies have shown that the downregulation of parasite-specific cellular immune response in brugia-infected jirds requires viable worms but is not dependent on microfilariae (mf) for either induction or maintenance of this phenomenon. to clarify further which life cycle stages induce filarial hyporesponsiveness, jirds were infected intraperitoneally with third stage larvae (l3) exposed to 0, 15, 25, 35, 45, or 90 krad of gamma radiation to differentially alter l3 development. necropsies ...19979406789
characteristics of nucleotide sequences flanking the trans-spliced leader sl1 exon in dirofilaria immitis, brugia malayi, and brugia pahangi.nucleotide sequences surrounding the trans-spliced leader sl1 exon in the 5s rrna gene spacer regions of dirofilaria immitis, brugia malayi, and b. pahangi were determined after pcr amplification, aligned with the genus onchocerca for comparison, and used for the prediction of secondary structures. the nucleotide sequence of this region in b. pahangi was first shown in the present study. hypothetical secondary structures of the spacer region suggested that the sl1 transcript is capable to form a ...19979450246
modelling variability in lymphatic filariasis: macrofilarial dynamics in the brugia pahangi--cat model.a striking feature of lymphatic filariasis is the considerable heterogeneity in infection burden observed between hosts, which greatly complicates the analysis of the population dynamics of the disease. here, we describe the first application of the moment closure equation approach to model the sources and the impact of this heterogeneity for macrofilarial population dynamics. the analysis is based on the closest laboratory equivalent of the life cycle and immunology of infection in humans--cats ...19989474798
down regulation of macrophage activation in brugia pahangi-infected jirds (meriones unguiculatus).the macrophage is a major component of the inflammatory response induced by lymphatic tissue-dwelling filariae. intraperitoneal (i.p.) infections with brugia pahangi in mongolian gerbils, or jirds (meriones unguiculatus), induce a peritoneal inflammatory response characterized by accumulation of numerous macrophages and fewer eosinophils. this inflammatory response is associated with the release of microfilariae by female worms. the aim of this study was to investigate the activation state of th ...19989488396
variability among tunisian populations of culex pipiens: genetic structure and susceptibility to a filarial parasite, brugia pahangi.culex pipiens pipiens is a common mosquito found in north africa and is the primary vector of bancroftian filariasis in egypt. experimental infections with c. p. pipiens have demonstrated that this species supports brugia pahangi development (parasitic yield 6.3%). in addition, the genetic variation among c. p. pipiens populations from ben arrous (in the suburb of tunis) estimated from isoenzyme polymorphism of five neutral genes (pgm, gpi, hk1, got-1, and got-2) was slight (fst = +0.083). c. p. ...19989493214
dirofilaria immitis: molecular cloning and expression of a cdna encoding a selenium-independent secreted glutathione peroxidase.a cdna clone, di29, encoding a homolog of glutathione peroxidase, was isolated from a dirofilaria immitis adult female cdna expression library by a combination of polymerase chain reaction amplification with primers designed from the brugia pahangi glutathione peroxidase gene sequence and hybridization screening of d. immitis cdna libraries. the di29 nucleotide and deduced amino acid sequences were very similar to those described for lymphatic filariae and predicted a secreted form of glutathion ...19989501847
a novel member of the transforming growth factor-beta (tgf-beta) superfamily from the filarial nematodes brugia malayi and b. pahangi.transforming growth factor-beta (tgf-beta) superfamily genes encode products controlling pattern formation, cell differentiation, and immune-mediated inflammation. members of this superfamily are known in multicellular organisms from mammals to the model nematode caenorhabditis elegans. using pcr with oligonucleotides complementary to highly conserved motifs in the tgf-beta superfamily, we first isolated a genomic clone from the filarial nematode brugia malayi. this gene, termed bm-tgh-1 (tgf-be ...19989562423
cloning and characterization of cdnas encoding beta-tubulin from dirofilaria immitis and onchocerca volvulus.beta-tubulin is the target for the benzimidazole anthelmintics. unfortunately, none of these drugs is clinically useful against adult filariae. however, beta-tubulin has been shown to be a target for antibody-based toxicity to brugia pahangi. we cloned and characterized cdnas encoding beta-tubulin from 2 filariae, dirofilaria immitis and onchocerca volvulus, to explore possible explanations for benzimidazole insensitivity among adult filariae and the likelihood that epitopes of beta-tubulin coul ...19989576511
formation of basement membrane-like structure terminates the cellular encapsulation of microfilariae in the haemocoel of anopheles quadrimaculatus.the encapsulation of microfilariae in the haemocoels of mosquitoes combines both humoral and cellular reactions: the microfilariae are first encased in an acellular layer of melanin, followed by a cellular encapsulation by plasmatocytes. in this study, we demonstrated that cellular encapsulation of brugia pahangi microfilariae in the haemocoel of the mosquito anopheles quadrimaculatus was terminated by the formation of a basement membrane-like structure on the outermost surface of the cellular c ...19989651933
characterisation of tc-cpl-1, a cathepsin l-like cysteine protease from toxocara canis infective larvae.cysteine proteases play vital biological roles in both intracellular and extracellular environments. a cysteine protease migrating at 30 kda was identified in somatic extracts of toxocara canis larvae (tex), by its binding to the biotinylated inhibitor phe-ala-ch2f. tex proteases readily cleaved the cathepsin l- and b-specific peptide substrate z-phe-arg-amc and to a lesser extent, the cathepsin b-specific peptide z-arg-arg-amc. excretory/secretory (tes) products of t. canis larvae did not cleav ...19989657332
association of elevated lymph node cell release of histamine and tumor necrosis factor with genetic predisposition to limb edema formation in dogs infected with brugia pahangi.brugia pahangi infection in the canine rear limb results in marked lymphatic duct and popliteal lymph node pathologic changes. limb edema is variably associated with infection and does not correlate well with duct or node lesions. to understand the mechanisms of limb edema, lymph node cells were collected by sequential biopsy following infection and examined for production of inflammatory mediators. lymph node cells from a litter of dogs selectively bred with a high incidence of edema formation ...19989660448
dirofilaria immitis and brugia pahangi: filarial parasites make nitric oxide. 19989709039
in vitro antifilarial activity of organometallic complexes against infective larvae of molinema dessetae and adult females of brugia pahangi.new organometallic complexes having protozoocidal properties were evaluated for their in vitro antifilarial activity using two models: infective larvae of molinema dessetae and adult females of brugia pahangi. the compound most active on the m. dessetae model was ir(i)-cod-pentamidine tetraphenylborate with an ec50 = 6 +/- 1 microm after 7-day-incubation. in the 2-aminobenzothiazole series, ruthenium was more potent than iridium for antifilarial activity. a dithiocarbamate function significantly ...19989762575
bis-cationic heteroaromatics as macrofilaricides: synthesis of bis-amidine and bis-guanylhydrazone derivatives of substituted imidazo[1,2-a]pyridines.a series of guanylhydrazone, amidine, and hydrazone derivatives of 2-phenylimidazo[1,2-a]pyridine have been prepared and evaluated for macrofilarial activity against acanthocheilonema viteae and brugia pahangi in jirds. compounds with 4',6-bis-substitution by cyclic guanylhydrazone groups show activity. 4',6-bis-amidines show some activity but are more toxic; 4'- or 6-monosubstituted compounds are inactive. 2,6-bis-substituted compounds lacking the phenyl ring are inactive. 4',6-bis-substituted ...19989784107
rapid purification and characterization of l-dopachrome-methyl ester tautomerase (macrophage-migration-inhibitory factor) from trichinella spiralis, trichuris muris and brugia pahangi.macrophage-migration-inhibition factor (mif) is an essential stimulator of mammalian t-lymphocyte-dependent adaptive immunity, hence mif orthologues might be expressed by infectious organisms as an immunosubversive stratagem. since mif actively catalyses the tautomerization of the methyl ester of l-dopachrome (using dopachrome tautomerase), the occurrence of mif orthologues in several parasitic helminths was investigated by assaying and characterizing such activity. evidence of mif orthologues ( ...19989794786
the l3 of brugia induces a th2-polarized response following activation of an il-4-producing cd4-cd8- alphabeta t cell population.lymphatic filariasis in man is characterized by a profound bias in the immune response. parasite-specific th1 responses are dramatically down-regulated while th2 responses dominate. we have used the infective larval stage of the nematode parasite brugia pahangi, a potent th2 inducer in naive mice, to examine cytokine production during the initiation phase of the response. for comparative purposes, the early cytokine transcription pattern elicited by microfilariae (mf), another life cycle stage o ...19989796925
granulomatous inflammatory response to recombinant filarial proteins of brugia species.the lymphatic inflammatory response in brugia-infected jirds peaks early during primary infections and then decreases in severity as judged by the numbers of lymph thrombi present within these vessels. antigen-specific hypersensitivity reactions in these animals was measured by a pulmonary granulomatous inflammatory response (pgrn) induced by somatic adult worm antigen (sawa)-coated beads, and by cellular proliferative responses of renal lymph node cells. the kinetics of these responses temporal ...199910072145
interleukin-10 and antigen-presenting cells actively suppress th1 cells in balb/c mice infected with the filarial parasite brugia pahangi.infection with the third-stage larvae (l3) of the filarial nematode brugia results in a th2-biased immune response in mice and humans. previously we have shown that the production of interleukin 4 (il-4) is critical for down-regulating polyclonal th1 responses in l3-infected mice. however, the in vitro neutralization of il-4 did not fully recover the defective polyclonal th1 responses, nor did it result in the production of any antigen (ag)-specific th1 cytokines, suggesting that perhaps infecti ...199910084992
16s rdna phylogeny and ultrastructural characterization of wolbachia intracellular bacteria of the filarial nematodes brugia malayi, b. pahangi, and wuchereria bancrofti. 199910092480
identification of a molecular marker for the y chromosome of brugia malayi.random amplification of polymorphic dna (rapd) was used to analyse genomic dna from virgin females and males of brugia malayi, with a view to identifying sex-specific differences predicted by an xx/xy system of chromosomal sex determination. a product of 2338 bp, amplified with the arbitrary primer 5' gttgcgatcc 3', was obtained exclusively from males. primers based on the sequence of this product amplified a dna fragment of the expected size from each of two independent isolates of b. malayi (f ...199910215019
effects of tetracycline on the filarial worms brugia pahangi and dirofilaria immitis and their bacterial endosymbionts wolbachia.wolbachia endosymbiotic bacteria have been shown to be widespread among filarial worms and could thus play some role in the biology of these nematodes. indeed, tetracycline has been shown to inhibit both the development of adult worms from third-stage larvae and the development of the microfilaraemia in jirds infected with brugia pahangi. the possibility that these effects are related to the bacteriostatic activity of tetracycline on wolbachia symbionts should be considered. here we show that te ...199910221636
brugia pahangi: quantitative analysis of infection in several inbred rat strains.we report a comprehensive study of the infectivity of brugia pahangi in male and female rats of eight different inbred strains. a single infection of any inbred rat strain will produce rats that become microfilaremic, have occult infection, or clear the primary infection. the proportion belonging to any category is determined by the basic susceptibility level of that strain. patency rates (blood microfilaria+) ranged from 24% (ao rats) to 73% (wka rats). the period for which microfilaria were in ...199910366537
preliminary results on the effect of tetracycline on the embryogenesis and symbiotic bacteria (wolbachia) of dirofilaria immitis. an update and discussion.the distribution and phylogeny of wolbachia in filarial species suggests that these endosymbiotic bacteria may be important in the biology of their filarial hosts. an experiment to falsify this hypothesis would be to treat filarial worms with antibiotics which are active against intracellular bacteria. indeed, it has already been shown that tetracycline treatment inhibits development in a model filarial species (brugia pahangi) at different stages of the life cycle, in both mosquito and mammalia ...199810376278
cut-1-like genes are present in the filarial nematodes, brugia pahangi and brugia malayi, and, as in other nematodes, code for components of the cuticle.a fragment of a cut-1 like gene from the filarial nematode brugia pahangi (designated bp-cut-1) was isolated by pcr from genomic dna. the sequence was used to design primers for use in rt-pcr and resulted in the isolation of a cdna fragment from larvae in the process of the l3-l4 moult. screening of a b. malayi genomic library identified a single clone, bm-cut-1. using primers designed from the brugia sequences, semi-quantitative rt-pcr was carried out on 11 different life cycle stages chosen to ...199910413052
the isolation of differentially expressed cdna clones from the filarial nematode brugia pahangi.a cdna library constructed from 3 day post-infective l3 of the filarial nematode brugia pahangi was screened by differential hybridization with cdna probes prepared from different life-cycle stages. five cdna clones hybridizing selectively to the mosquito-derived l3 probe were isolated and characterized. northern blot analysis of 4 of the clones confirmed that each was most highly expressed in the mosquito-derived l3. the expression of each mrna during parasite development in the mosquito vector ...199910466127
cloning and characterization of two nuclear receptors from the filarial nematode brugia pahangi.nuclear receptors (nrs) encompass a superfamily of cytoplasmic/nuclear localized receptors that on ligand binding (or by phosphorylation) directly regulate the transcription of target genes. nrs are involved in many developmental processes, including moulting in insects and dauer larva formation in caenorhabditis elegans. here we report the isolation of two genes related to nrs from the filarial nematode brugia pahangi. bp-nhr-1 is a member of the ngf1-b subfamily of nrs and is expressed at very ...199910548557
up-regulation of extracellular copper/zinc superoxide dismutase mrna after transmission of the filarial parasite acanthocheilonema viteae in the vertebrate host meriones unguiculatus.the gene encoding the cytoplasmic copper/zinc superoxide dismutase (avsod1) from the filarial parasite acanthocheilonema viteae was isolated from a genomic dna library using a degenerate oligonucleotide probe. additionally, cdnas of the avsod1 and the secreted extracellular sod (avsod2) were both cloned by rt-pcr, and the avsod2 was expressed at high levels in e. coli. the amino acid sequence of the avsod1 is 89.5 and 87.5% identical to that of the corresponding enzymes of brugia pahangi and onc ...199910579430
development of a pcr- and probe-based test for the sensitive and specific detection of the dog heartworm, dirofilaria immitis, in its mosquito intermediate host.the mosquito-borne filarial worm, dirofilaria immitis, causes heartworm disease in dogs. detection of this parasite in its mosquito intermediate host currently involves dissection and microscopic examination for larval stages. although this method is used commonly as a screening tool for epidemiological surveys, it lacks both sensitivity and specificity. in this study, a more efficient pcr- and probe-based diagnostic assay was developed. the target selected for this assay is a segment of the 16 ...199910657147
b1 b lymphocytes play a critical role in host protection against lymphatic filarial parasites.host defense against multicellular, extracellular pathogens such as nematode parasites is believed to be mediated largely, if not exclusively, by t lymphocytes. during our investigations into the course of brugia malayi and brugia pahangi infections in immunodeficient mouse models, we found that mice lacking b lymphocytes were permissive for brugian infections, whereas immunocompetent mice were uniformly resistant. mice bearing the btk(xid) mutation were as permissive as those lacking all b cell ...200010684864
polyamines: agents with macrofilaricidal activity.there is a need for effective macrofilaricidal drugs. the polyamine metabolism of filarial worms has been recognized as a possible target for effective drug action. in an attempt to identify agents that might provide leads in developing an effective macrofilaricide, 78 polyamine compounds were selected from among > 250,000 structures that have been amassed by the walter reed army institute of research, in the u.s.a. these thousands of agents have been chosen principally for drug-development prog ...199910715679
hmg-coa reductase inhibitor induces a transient activation of high affinity nerve growth factor receptor, trk, and morphological differentiation with fatal outcome in pc12 cells.the present study was aimed at investigating the possible toxicity of simvastatin on a neuronal cell line, pc12 cells. simvastatin clearly induced a transient morphological differentiation as evidenced by the occurrence of neurite outgrowth with a transient activation of the high affinity nerve growth factor receptor, trk, but died at 36 h after its addition. tyrosine autophosphorylation of the trk protein also disappeared at 36 h after addition. during the morphological differentiation, ngf mrn ...200010720627
differential diagnosis of human lymphatic filariasis using pcr-rflp.filariasis is still a public health problem in tropical countries. the most common causative agents of human filariasis are wuchereria bancrofti and brugia malayi. traditional methods used to detect filarial parasites in human, animal and vector populations are tedious, time consuming, and confer little guarantee of sensitivity and species specificity. we have developed a rapid and specific method to detect filarial parasite dnas in blood and mosquito samples using the polymerase chain reaction ...200010722791
pharmacokinetics of umf-078, a candidate antifilarial drug, in infected dogs.the pharmacokinetics of the filaricidal benzimidazole compounds umf-078 and umf-289 were evaluated in beagle dogs experimentally infected with brugia pahangi. twenty-four infected microfilaremic beagles were selected and randomly allocated into 4 treatment groups of 6 dogs each: oral (po) umf-078, po umf-289 (the hcl salt form of umf-078), intramuscular (im) umf-078, and untreated controls. equivalent doses of 50 mg/kg of the free base were given twice a day for 3 days to the 3 groups of treated ...200010761730
anticancer agents suppressive for adult parasites of filariasis in mongolian jirds.eight chemical structures not previously reported to possess antifilarial activity have been identified. a total of 79 compounds with anticancer properties were evaluated for possible macrofilaricidal activity against brugia pahangi and acanthocheilonema viteae transplanted into male mongolian jirds (meriones unguiculatus). all eight active compounds were suppressive for the onchocerciasis type (acanthocheilonema viteae) of the disease. none was macrofilaricidal for the lymphatic form (brugia pa ...200010782046
in vitro antifilarial activity of extracts of the medicinal plant cardiospermum halicacabum against brugia pahangi.the in vitro effects of ethanol and aqueous extracts of the medicinal plant cardiospermum halicacabum on adult worms and microfilariae of brugia pahangi were investigated. with or without the plant extracts in culture medium, the motility of adult worms, microfilariae and microfilarial release from female worms were monitored daily. after 7 days of culture, viability or tissue damage of adult worms was assessed using the mtt assay. at > 500 microg ml-1, the aqueous extract significantly reduced ...200010953224
no contributes to proliferative suppression in a murine model of filariasis.infection of balb/c mice with microfilariae (mf) of brugia pahangi leads to the suppression of antigen (ag)-specific proliferative responses in the spleen. the proliferative defect is dependent on inducible nitric oxide synthase (inos) activity, since inhibition of inos with either l-n-monomethyl arginine (l-nmma) or aminoguanidine reversed defective proliferation. splenocytes from mf-infected animals produce high levels of gamma interferon (ifn-gamma) upon in vitro restimulation with ag, and ex ...200011035712
differential susceptibility to brugia pahangi infection in mongolian gerbils (meriones unguiculatus) of different coat colour.the influence of intraspecific host variables on the response to parasitic infections is an important aspect of host-parasite relationships, yet little is known about this aspect of filariasis for lack of a model. this study presents coat colour mutants of the mongolian gerbil (meriones unguiculatus) as potential new models for research into the effects of host genetic variation on response to filarial infection. peak level of microfilaraemia, eosinophil response, body weight and degree of splen ...200011037123
tetracycline inhibits development of the infective-stage larvae of filarial nematodes in vitro.in recent years, studies have linked tetracycline treatment of filaria-infected animals with reduced adult worm burdens and decreased levels of microfilaremia. these observations are believed to be attributable to clearance of wolbachia, intracellular rickettsial-like organisms found within filarial tissues. although maximal worm reductions were observed when treatment was initiated early in infection, it is not known whether tetracycline inhibits development of infective-stage larvae. to addres ...200011038309
identification and localization of glutathione s-transferase as a potential target enzyme in brugia species.brugia filarial nematodes are pathogenic lymphatic-dwelling parasites that, like other helminths, may modify the host's defense mechanisms by a major detoxification process involving glutathione-binding proteins such as glutathione s-transferases (gsts). in the present study, soluble extracts of third-stage larvae, adult male and female worms, microfilariae of either b. pahangi or b. malayi or the adult worm excretory-secretory products of b. malayi were used to determine gst activity. these ext ...200011097299
temperature is a cue for gene expression in the post-infective l3 of the parasitic nematode brugia pahangi.the temporal expression pattern of two genes, bp-cdd and bp-s3, was studied at defined points throughout the life cycle of brugia pahangi. both mrnas were up-regulated to coincide with the transition of the l3 from the vector to the mammalian host. bp-cdd was expressed almost exclusively in the post-infective (p.i.) l3 and l4 stages of the life cycle while bp-s3 was also expressed in adult worms, but at a much lower level than in the larval stages. immunogold labelling with an antiserum raised t ...200111166381
comparative development of brugia pahangi and variation in acid hydrolase enzyme titers in.the development of the filarial nematode brugia pahangi was monitored and compared in susceptible (black eye) and refractory (rock) strains of aedes aegypti. simultaneously, the activities of acid phosphatase, beta-glucuronidase, alpha-glucosidase, and n-acetyl-beta-glucosaminidase were measured. three- to five-day-old females of both strains were fed on infected and uninfected clawed jirds (meriones unguiculatus) then dissected or homogenized at 2 h, at 24-h intervals for 5 days, and at 8 and 1 ...200011198915
potential transition state phosphoramidate inhibitors of beta-tubulin as antifilarial agents.transition state phosphoramidate inhibitors of beta-tubulin were designed as potential antifilarial agents. the reaction of 2-aminobenzimidazole with diisopropyl phosphite and carbon tetrachloride at a low temperature gave the unexpected 1-diisopropoxyphosphoryl-2-aminobenzimidazole, which on heating gave the novel benzimidazole derivative, 2-(diisopropoxyphosphoryl)aminobenzimidazole. both products were fully characterized and the synthetic procedure to both compounds was optimized. the procedu ...200111206197
antibiotics and wolbachia in filarial nematodes: antifilarial activity of rifampicin, oxytetracycline and chloramphenicol against onchocerca gutturosa, onchocerca lienalis and brugia pahangi.the activity against filarial parasites of the antibiotics rifampicin, oxytetracycline and chloramphenicol was examined. in addition, transmission electron microscopy was used to study the effects of rifampicin and oxytetracycline on filarial tissues and on the endosymbiont bacterium, wolbachia. when tested in vitro at a concentration of 50.0 microm, each of the three antibiotics significantly reduced the motility levels of male onchocerca gutturosa. rifampicin, however, was the most active, vir ...200011214099
electrophysiological analysis of responses of adult females of brugia pahangi to some chemicals.electrophysiological techniques were used to obtain recordings of extracellular electrical activity from the anterior end of live adult females of brugia pahangi. stimulation with 100 mm, 10 mm and 1 mm acetylcholine resulted in an increase in spike activity which was concentration dependent, whereas stimulation with phosphate-buffered saline and 0.1 mm acetylcholine gave no increase in activity. the delay in response was not concentration dependent. the action of possible host cues was investig ...200111289071
antibody responses of wuchereria bancrofti patients to recombinant brugia pahangi superoxide dismutase.lymphatic filarial parasite brugia malayi contains significant amount of cu/zn superoxide dismutase (sod) activity in the extract of different life stages and in the excretory-secretory product of adults. in the present study recombinant sod from b. pahangi has been used to see the antibody response in wuchereria bancrofti infected patients. the recombinant sod from b. pahangi reacted specifically with w. bancrofti infected sera in elisa and immunoblotting. the reactivity of igm subclass was mor ...200111349523
analysis of the sensory responses of parasitic nematodes using electrophysiology.use of the electrophysiological technique to examine the sensory perception of live, intact nematodes has provided detailed analysis of responses to known concentrations of test chemicals. the use of larger nematodes, such as the animal-parasite syngamus trachea, enabled direct extracellular recordings from individual sensilla; with smaller nematodes, the recording electrode was inserted close to the cephalic region. extracellular recordings from the cephalic region of second-stage juveniles and ...200111406140
wolbachia in filarial nematodes: evolutionary aspects and implications for the pathogenesis and treatment of filarial diseases.the presence of intracellular bacteria in the body of various species of filarial nematodes, including important parasites such as brugia malayi, dirofilaria immitis, and onchocerca volvulus, was observed as early as the mid-1970s. these bacteria were shown to be transovarially transmitted (from the female worm to the offspring) and to be present in significant amounts in the body of the nematode. as highlighted by their discoverers, the potential importance of these bacteria is fairly obvious: ...200111516587
heat shock and developmental expression of hsp83 in the filarial nematode brugia pahangi.hsp83 was cloned from the filarial nematode brugia pahangi. the mrna was constitutively expressed at 37 degrees c in life cycle stages that live in the mammalian host (microfilariae and adult worms). heat shock resulted in only a minimal increase in levels of transcription. a genomic copy of hsp83 was isolated and was shown to contain 11 introns while sequencing of the 5' upstream region revealed several heat shock elements. using a chloramphenicol acetyltransferase (cat) reporter gene construct ...200111722567
cloning and characterisation of mmc-1, a microfilarial-specific gene, from brugia pahangi.nine differentially expressed genes were cloned from brugia pahangi in a screen which sought to identify cdnas that were differentially expressed between the microfilariae from the mammalian host and the mosquito vector. one gene (mmc-1), that was up-regulated in mammalian-derived microfilariae, was characterised in detail. rt-pcr analysis demonstrated that mmc-1 was specific to the microfilarial stage of the life cycle and was not transcribed by developing microfilariae in utero, but only follo ...200211849638
interleukin-4 influences the production of microfilariae in a mouse model of brugia infection.sub-cutaneous infection of interleukin (il)-4-/- mice on the balb/c background with third stage larva (l3) of brugia pahangi revealed an altered cytokine profile consistent with the absence of the th2 promoting cytokine il-4. splenocytes from il-4-/- mice secreted significantly more antigen (ag)-specific il-2 and interferon-gamma and significantly less ag-specific il-5, compared to those from l3-infected wild-type mice. however, levels of ag-specific il-13 were similar between groups. despite th ...200211856444
infection with brugia microfilariae induces apoptosis of cd4(+) t lymphocytes: a mechanism of immune unresponsiveness in filariasis.in humans infected with lymphatic filariasis, microfilaraemia [the presence of microfilariae (mf) in the blood] is generally associated with both poor antigen (ag)-specific proliferative responses and with protection from severe disease. clonal deletion has been suggested as one possible mechanism by which parasite-reactive lymphocytes, that may be capable of mediating resistance and/or immunopathology, are silenced in asymptomatic carriers. in this study we demonstrate that splenic lymphocytes ...200211870630
nk t cells are a source of early interleukin-4 following infection with third-stage larvae of the filarial nematode brugia pahangi.infection of c57bl/6 mice with the third-stage larvae of brugia pahangi results in a rapid expansion of nk1.1(+) t cells in the spleen and draining lymph nodes. nk t cells produced interleukin-4 in the spleen within 24 h of infection, and these cells were cd4(-).200211895990
brugian infections in the peritoneal cavities of laboratory mice: kinetics of infection and cellular responses.standard, immunocompetent, inbred strains of mice are non-permissive for infection with the human filarial nematode, brugia malayi or the closely related brugia pahangi. this non-permissiveness allows one to address the mechanism(s) that might be used by mammalian hosts to eliminate large, multicellular, metazoan, extracellular invertebrate pathogens. we describe here the time course of intraperitoneal brugian infections in naïve and primed +/+ mice from two commonly used, inbred laboratory stra ...200212128050
expression of the filarial nematode phosphorylcholine-containing glycoprotein, es62, is stage specific.es62, an immunomodulatory phosphorylcholine-containing glycoprotein secreted by the rodent filarial nematode acanthocheilonema viteae, has previously been shown to be produced by l4 larvae and adult worms only. however, homologous sequences to es62 have recently been found in l1 and l3 cdna libraries of certain human filarial nematodes. therefore, the various stages of a. viteae were re-examined and it was again found that only the post-l3 stages secreted es62. synthesis but not secretion by ear ...200212211608
pharmacokinetics and dose proportionality of oral moxidectin in beagle dogs.to study the pharmacokinetics and dose proportionality of moxidectin in beagle dogs experimentally infected with the filarial parasite brugia pahangi, and to evaluate and compare the results obtained from population pharmacokinetic analysis and individual compartmental analysis.200212355577
cloning and expression analysis of two mucin-like genes encoding microfilarial sheath surface proteins of the parasitic nematodes brugia and litomosoides.in several filarial genera the first stage larvae (microfilariae) are enclosed by an eggshell-derived sheath that provides a major interface between the parasite and the host immune system. analysis of the polypeptide constituents of the microfilarial sheath from the cotton rat filaria litomosoides sigmodontis identified two abundant surface glycoproteins: shp3a and shp3. the corresponding genes and the orthologues of the human parasite brugia malayi and the rodent filaria brugia pahangi were cl ...200212356773
infection outcome and cytokine gene expression in brugia pahangi- infected gerbils (meriones unguiculatus) sensitized with brucella abortus.filarial infections have been associated with the development of a strongly polarized th2 host immune response and a severe impairment of mitogen-driven proliferation and type 1 cytokine production in mice and humans. the role of this polarization in the development of the broad spectra of clinical manifestations of lymphatic filariasis is still unknown. recently, data gathered from humans as well as from immunocompromised mouse models suggest that filariasis elicits a complex host immune respon ...200212379668
nitric oxide limits the expansion of antigen-specific t cells in mice infected with the microfilariae of brugia pahangi.infection of balb/c mice with the microfilariae (mf) of the filarial nematode brugia pahangi results in an antigen-specific proliferative defect that is induced by high levels of no. using carboxyfluorescein diacetate succinimydl ester and cell surface labeling, it was possible to identify a population of antigen-specific t cells from mf-infected balb/c mice that expressed particularly high levels of cd4 (cd4(hi)). these cells proliferated in culture only when inducible no synthase was inhibited ...200212379675
tetracycline treatment and sex-ratio distortion: a role for wolbachia in the moulting of filarial nematodes?filarial nematodes harbour intracellular bacteria of the genus wolbachia. these bacteria are thought to be beneficial to the host nematode. indeed, tetracycline treatments reduce the population of wolbachia in filarial worms and have detrimental effects on the nematode. even though various antibiotic-curing experiments have been performed on filariae, the actual role of wolbachia in the biology of these nematodes is not yet clear. to address this issue, we designed a first experiment on a model ...200212392911
real-time pcr for quantification of the bacterial endosymbionts (wolbachia) of filarial nematodes.filarial nematodes harbour intracellular symbiotic bacteria belonging to the genus wolbachia. wolbachia is thought to play an important role in the biology of the nematode. moreover, wolbachia appears to be involved in the immunopathogenesis of filariasis and in the onset of the side-effects of antifilarial therapy. investigations in these research areas require reliable methods to quantify wolbachia both in nematodes and in vertebrate tissues. to this purpose, we designed a quantitative real-ti ...200112402526
effects of brugia pahangi infection on the cardiovascular system of stroke-prone spontaneously hypertensive rats.to determine if filarial infection causes any effect on the cardiovascular system of the host animal, stroke-prone spontaneously hypertensive rats were infected with brugia pahangi under the assumption that these rats would reveal pathological changes more clearly and in a shorter period than would ordinary rats. the infection resulted in loss of body weight, increase in heart weight, enlargement of left ventricle, and higher mortality rate.200212435117
lymphatic filariasis-specific immune responses in relation to lymphoedema grade and infection status. i. cellular responses.the filariasis-specific cellular responsiveness was assessed in 109 adult individuals from a wuchereria bancrofti-endemic area in north-east tanzania. there were 9 study groups. five groups of individuals were negative for microfilariae (mf) and specific circulating filarial antigen (cfa) and had leg lymphoedema of varying severity ranging from early to more advanced grades (pathology groups 1-5). another group comprised individuals with mixed grades of lymphoedema and positive for mf and/or cfa ...200212497986
lymphatic filariasis-specific immune responses in relation to lymphoedema grade and infection status. ii. humoral responses.the filarial-specific humoral responses (igg1, igg2, igg3, igg4 and ige) to a brugia pahangi antigen was assessed in 9 groups of adult individuals from a wuchereria bancrofti-endemic area in north-east tanzania. in 5 of the groups, individuals were negative for microfilariae (mf) and circulating filarial antigen (cfa) and had leg lymphoedema of varying severity ranging from early to more advanced grades. a 6th group had mixed grades of lymphoedema and were actively infected with mf and/or cfa. t ...200212497987
[achievements in the research on filariasis in china in the past 50 years]. 199912563852
primed peritoneal b lymphocytes are sufficient to transfer protection against brugia pahangi infection in mice.lymphatic filariasis is a tropical disease caused by the nematode parasites wuchereria bancrofti and brugia malayi. whereas the protective potential of t lymphocytes in filarial infection is well documented, investigation of the role of b lymphocytes in antifilarial immunity has been neglected. in this communication, we examine the role of b lymphocytes in antifilarial immunity, using brugia pahangi infections in the murine peritoneal cavity as a model. we find that b lymphocytes are required fo ...200312595454
pcr-based detection and identification of the filarial parasite brugia timori from alor island, indonesia.brugia timori is widely distributed on alor island, indonesia, where it causes a high degree of morbidity. the hhai tandem repeat of b. timori was found to be identical to that of b. malayi, for which sensitive pcr-based assays have already been developed. using one of these assays, a single microfilaria (mf) of b. timori, present in a spot of dry blood on filter paper, could be detected. the assay was equally sensitive in the detection of b. timori and b. malayi. when the collected mosquitoes w ...200212625936
immunohistochemical/immunogold detection and distribution of the endosymbiont wolbachia of dirofilaria immitis and brugia pahangi using a polyclonal antiserum raised against wsp (wolbachia surface protein).intracellular bacteria in filarial nematodes were described as early as the 1970s, yet it was only with the work on dirofilaria immitis, the agent of canine and feline heartworm disease, that these microorganisms were identified as belonging to wolbachia, a genus known for encompassing bacteria infecting insects and other arthropods. the implications for the presence of intracellular bacteria in filarial nematodes is now the subject of intense research, particularly regarding their role in the i ...200312632152
chemotactic response of brugia pahangi infective larvae to jird serum in vitro.the brugia pahangi infective larval response to jird serum was studied using an agar plate assay. larvae placed onto the agar remained at the same place for 60 min. once the larvae were stimulated by serum, more than 95% oriented towards the serum and reached it within few minutes. this larval response was inhibited by an activator of phosphodiesterase (imidazole), adenylate cyclase inhibitors (sq22536 and mdl-12330a) and protein kinase a inhibitor. an inhibitor of phosphodiesterase (ibmx), an a ...200312695907
brugia pahangi and wolbachia: the kinetics of bacteria elimination, worm viability, and host responses following tetracycline treatment.wolbachia spp., first reported from filariae nearly 30 years ago, have been suggested to contribute to the pathogenesis associated with human filarial infection. tetracycline has been used to cure filariae of wolbachia, as a novel means of chemotherapeutic treatment for both ocular and lymphatic filariasis. tetracycline treatment of l4 or adult brugia pahangi in vivo resulted in wolbachia clearance. less tetracycline was required to clear wolbachia when treatment began at the l4 stage, compared ...200312810042
kinetics of cellular responses to intraperitoneal brugia pahangi infections in normal and immunodeficient mice.filarial infections evoke exuberant inflammatory responses in the peritoneal cavities of immunocompetent mice. clearance of infection appears to be dependent on complex interactions between b1 and b2 b lymphocytes, t cells, eosinophils, macrophages, and the products of these cells. in an earlier communication, we described the course of infection in normal immunocompetent mice. in this study, we utilize mice with well-characterized mutations that disable one or more effector components of adapti ...200312874313
effect of immunostimulatory oligodeoxynucleotides on host responses and the establishment of brugia pahangi in mongolian gerbils (meriones unguiculatus).infection of humans with filarial parasites has long been associated with the maintenance of a dominant th2-type host immune response. this is reflected by increases in interleukin (il)-4- and il-5-producing t cells, elevated immunoglobulin (ig)e and igg4 levels, and a pronounced eosinophilia. the mongolian gerbil (meriones unguiculatus) is permissive for the filarial nematodes brugia malayi and b. pahangi. as in humans, persistent microfilaremic infections of gerbils with brugia spp. results in ...200312880245
the effects of common salt on aedes togoi and filarial infection.the effects of salt on the development of aedes togoi and the infecton of brugia pahangi were studied. salt concentrations over 7.2% completely got rid of pupae and adults. the salt concentrations 0% to 3.6% reduced pupal development from 86.6% to 72.8% and adult from 70.3% to 53.3%. b. pahangi infestations and infection rates were also reduced in the mosquitoes reared at salt concentrations of 1.8% and 3.6%. trends of retardation in the filarial development were observed when the salt concentra ...198212902695
a preliminary account of the transmission, maintenance and laboratory vectors of brugia pahangi. 196013725689
developmental stages of brugia pahangi in the final host. 196213976564
morphology of the microfilaria of brugia pahangi and of the larval stages in the mosquito. 196213976565
comparative migration of microfilariae and development of brugia pahangi in various mosquitoes. 196514270450
exsheathment of the microfilariae of brugia pahangi in susceptible and refractory mosquitoes. 196514270451
fate of transplanted third-stage brugia pahangi larvae in normally susceptible and nonsusceptible mosquito hosts. 196514275701
the application of fluorescent-antibody test to microfilariae of brugia pahangi. 196514303094
robust parameter estimation techniques for stochastic within-host macroparasite models.we present a stochastic model of the within-host population dynamics of lymphatic filariasis, and use a simulated goodness-of-fit (gof) method to estimate immunological parameters and their confidence intervals from experimental data. a variety of deterministic moment closure approximations to the stochastic system are explored and compared with simulation results. for the maximum gof parameter estimates, none of the methods of closure accurately reproduce the behaviour of the stochastic model. ...200314615200
a new class of anti-filariasis compounds: a preliminary look.parasitic nematode worms which produce filariasis in humans place approximately one billion people at risk in more than 75 countries. more than 100 million people are infected with these diseases and are recognized as being of significant military importance. during world war ii, filariasis was among the leading causes of medical evacuation from the entire south pacific area. agents available to treat the diseases exhibit significant toxicity. better drugs are urgently needed. data are reported ...199414620403
removal of wolbachia from brugia pahangi is closely linked to worm death and fecundity but does not result in altered lymphatic lesion formation in mongolian gerbils (meriones unguiculatus).approximately 30 years ago, researchers reported intracellular bacteria in filarial nematodes. these bacteria are relatives of the arthropod symbiont wolbachia and occur in many filarial nematodes, including brugia pahangi and brugia malayi. wolbachia bacteria have been implicated in a variety of roles, including filaria development and fecundity and the pathogenesis of lymphatic lesions associated with filarial infections. however, the role of the bacteria in worm biology or filarial disease is ...200314638788
impaired clearance of primary but not secondary brugia infections in il-5 deficient mice.eosinophilia in blood and tissues has been strongly associated with helminth infections for over a century. in vivo depletion of il-5, a cytokine crucially involved in eosinophilopoiesis with an antibody or through genetic manipulation, reproducibly abrogates helminth-induced eosinophilia, but renders mice permissive only in some models of parasite infection. in the current study, we compared the ability of il-5(-/-) and b6(+/+) mice to clear intraperitoneal infections with brugia pahangi l3. il ...200314969690
stage-specific and species-specific differences in the production of the mrna and protein for the filarial nematode secreted product, es-62.previous studies have shown that the secreted phosphorylcholine-containing glycoprotein of filarial nematodes, es-62, is only present in the post-infective life-cycle stages, but that the mrna is transcribed throughout the worm's life-cycle. the aim of this current study was to investigate whether the presence or absence of protein expression simply reflects differences in mrna abundance. to this end, we investigated the relative abundance of es-62 using taqman real time rt-pcr, in different lif ...200415002908
ultrastructural evidence of the degenerative events occurring during embryogenesis of the filarial nematode brugia pahangi after tetracycline treatment.intracellular bacteria belonging to the genus wolbachia have been described in filarial nematodes and these microorganisms appear to have evolved an obligatory mutualistic association with their filarial hosts. in fact, antibiotic treatment leads to the clearance of bacteria from worms resulting in a block in embryogenesis and, eventually, death of adult filariae. currently, the antifilarial action of antibiotic treatment is interpreted as a secondary consequence of the bacteriostatic activity a ...200315267003
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