| the capacity to produce ifn-gamma rather than the presence of interleukin-4 determines the resistance and the degree of susceptibility to leishmania donovani infection in mice. | the immune response against leishmania donovani infection has been investigated in one resistant mouse strain (c3h/hej) and three susceptible mouse strains (c57bl/6, balb/c, and b10d2/n). in order to correlate the strain-specific course of infection with the individual t cell response phenotype, the ex vivo cytokine secretion patterns of splenic lymphocytes were assessed by elisa (interferon-y [ifn-gamma], interleukin-4 [il-4], il-10) or by bioassay (il-2). the strain-dependent differences in th ... | 2000 | 10670653 |
| kala-azar in a high transmission focus: an ethnic and geographic dimension. | in 1994-1996, we studied a group of 58 game wardens stationed in an area known to be highly endemic for visceral leishmaniasis (kala-azar) for evidence of infection with leishmania donovani. leishmania dna was detected by the polymerase chain reaction in the peripheral blood of cases of active kala-azar, former patients with visceral leishmaniasis, patients, and asymptomatic subjects. using the cloned antigen rk39, antibodies were detected in 44.2% of the game wardens while leishmanin skin test ... | 1999 | 10674674 |
| epidemiologic aspects of american visceral leishmaniasis in an endemic focus in eastern venezuela. | an endemic focus of american visceral leishmaniasis (avl) in eastern venezuela has been evaluated in terms of patients (n = 48), immunologic reactivity to leishmania in household contacts (n = 187) and neighborhood controls (n = 170), detection of leishmania (l. donovani complex) in dogs and wild animals by the polymerase chain reaction (pcr) and characteristics of the sandfly population. the male:female ratio of patients was 1.18:1; 89.6% were < or =12 years old. serologic reactivity was signif ... | 1999 | 10674675 |
| four conserved cytoplasmic sequence motifs are important for transport function of the leishmania inositol/h(+) symporter. | the protozoan leishmania donovani has a myo-inositol/proton symporter (mit) that is a member of a large sugar transporter superfamily. active transport by mit is driven by the proton electrochemical gradient across the parasite membrane, and mit is a prototype for understanding the function of an active transporter in lower eukaryotes. mit contains two duplicated 6- or 7-amino acid motifs within cytoplasmic loops, which are highly conserved among 50 members of the sugar transporter superfamily a ... | 2000 | 10681553 |
| leishmania donovani infection of bone marrow stromal macrophages selectively enhances myelopoiesis, by a mechanism involving gm-csf and tnf-alpha. | alterations in hematopoiesis are common in experimental infectious disease. however, few studies have addressed the mechanisms underlying changes in hematopoietic function or assessed the direct impact of infectious agents on the cells that regulate these processes. in experimental visceral leishmaniasis, caused by infection with the protozoan parasite leishmania donovani, parasites persist in the spleen and bone marrow, and their expansion in these sites is associated with increases in local he ... | 2000 | 10688819 |
| the development of post-kala-azar dermal leishmaniasis (pkdl) is associated with acquisition of leishmania reactivity by peripheral blood mononuclear cells (pbmc). | pkdl develops in about 50% of sudanese patients treated for visceral leishmaniasis (kala-azar). patients with kala-azar were entered into this study and followed for a period of up to 2 years. during follow up 12 patients developed pkdl and eight did not. proliferative responses and cytokine production to leishmania donovani and control antigens were measured in vitro using pbmc isolated at the time of diagnosis of kala-azar, after treatment of visceral leishmaniasis, during follow up, and at th ... | 2000 | 10691926 |
| modulation of cd11c+ splenic dendritic cell functions in murine visceral leishmaniasis: correlation with parasite replication in the spleen. | balb/c mice resolve leishmania donovani infection in the liver over an 8-12-week period. however, after an initial phase of 2-4 weeks where increases in parasite load are not readily detectable, parasite numbers in the spleen begin to increase reaching maximum levels at 16 weeks post-infection. thereafter, parasite replication in the spleen is controlled and balb/c mice maintain this residual parasite load in the spleen for many months, without further increase. we evaluated functions of cd11c+ ... | 2000 | 10692051 |
| calcium mobilization by arachidonic acid in trypanosomatids. | a recent report (eintracht j, maathai r, mellors a, ruben l. calcium entry in trypanosoma brucei is regulated by phospholipase a, and arachidonic acid, biochem j 1998:336:659-66) provided evidence that calcium entry in trypanosoma brucei bloodstream trypomastigotes is regulated via a signaling pathway involving phospholipase a2-mediated generation of arachidonic acid and stimulation of a plasma membrane-located calcium channel. here we show that ca2+ influx in t. brucei procyclic trypomastigotes ... | 2000 | 10693748 |
| isolation and characterization of leishmania mutants defective in glycosomal protein import. | kinetoplastid parasites contain a unique microbody organelle called the glycosome. several important metabolic pathways found in the cytoplasm of higher eukaryotes are compartmentalized within the glycosome in these pathogens. this fundamental difference between the host and parasite has led to consideration of the glycosome as a potential chemotherapeutic target. the genetic basis of glycosome biogenesis is therefore of great interest. this report describes the isolation of multiple leishmania ... | 2000 | 10699252 |
| nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against leishmania infected macrophages. | a series of labdans and their derivatives have been identified as novel potential antileishmanial drugs using an in vitro test system against extracellular promastigotes and intracellular amastigotes of leishmania donovani in murine macrophages (kayser, o., kiderlen, a.f., 1998. in vitro activity of leishmanicidal labdanes and related compounds. proceedings of the ninth international congress of parasitology, monduzi editore, bologna, 925-929). of these compounds, aphidicolin, a tetradecanhydro- ... | 2000 | 10699730 |
| use of an attenuated leishmanial parasite as an immunoprophylactic and immunotherapeutic agent against murine visceral leishmaniasis. | the ability of the leishmanial parasite ur6 to act as an immunoprophylactic and immunotherapeutic agent against leishmania donovani infection in balb/c mice was investigated. unlike the virulent l. donovani ag83 (mohom/in/1983/ag83), ur6 given through intracardiac route failed to induce visceral infection, but when it was injected subcutaneously, ur6 induced a short-lived and localized self-healing skin lesion. priming of peritoneal macrophages with ur6 in vitro induced superoxide (o(2)(-)) gene ... | 2000 | 10702498 |
| use of urine samples from healthy humans, nephritis patients or other animals as an alternative to foetal calf serum in the culture of leishmania (l.) donovani in vitro. | the effect of supplementing in-vitro cultures of leishmania donovani with urine was investigated. the parasites were isolated from bangladeshi patients with visceral leishmaniasis. the urine samples used were collected from healthy human donors, patients with nephrotic syndrome, diabetic nephritis (dn) or diabetes mellitus, a dog and a cow. promastigotes from blood-agar cultures were inoculated into rpmi-1640 basal medium with 10% heat-inactivated foetal calf serum (fcs) and/or 1%-20% urine. the ... | 1999 | 10707106 |
| aetiology of visceral leishmaniasis in mexico. | two children with visceral leishmaniasis (vl), were studied by dna analysis. dna from liver biopsy samples from both patients, was amplified by pcr with broad primers specific for the leishmania subgenus. dna from the patient from chiapas was also amplified with primers specific for the leismania donovani complex and hybridised with a probe specific for l. donovani complex. the second patient, who is the first reported case of visceral leishmaniasis in the mexican state of tabasco, where localis ... | 2000 | 10708655 |
| uniform distribution of transcription complexes over the entire leishmania donovani clpb (hsp 100) gene locus. | we have analyzed the rna polymerase density on the leishmania donovani clpb gene locus. our results show an even distribution of rna polymerase over the clpb locus indicating an undiscriminative transcription. we conclude that, unlike the hsp70 genes, the clpb gene is not transcribed individually, but rather as part of a larger, polycistronic transcription unit. | 1999 | 10714771 |
| evaluation of a standardized direct agglutination test (dat) for the diagnosis of visceral leishmaniasis in kenya. | a prototype test kit being developed, by the world health organization (who), for the diagnosis of visceral leishmaniasis (vl) was evaluated in the baringo district of rift valley province in kenya. the screening of approximately 10,000 individuals for the signs of vl produced 305 suspected cases. these cases and 304 controls matched for sex and age (+/- 2 years) were then tested with the kit, which is based on a direct agglutination test (dat). the evaluation was a three-stage process. the firs ... | 1999 | 10715698 |
| heat-stress induced modulation of protein phosphorylation in virulent promastigotes of leishmania donovani. | in parasites such as leishmania, the study of molecular events induced in response to heat stress is of immense interest since temperature increase is an integral part of the life cycle. protein phosphorylation is known to control major steps of proliferation and differentiation in eukaryotic cells. studies on intracellular signaling systems in protozoa are relatively recent. we have examined the effect of heat shock on the protein phosphorylation status in promastigotes of leishmania donovani. ... | 2000 | 10716628 |
| cross-species homologous recombination in leishmania donovani reveals the sites of integration. | | 2000 | 10717308 |
| inhibition of interferon-gamma signaling by leishmania donovani. | leishmania infection causes marked down-regulation of interferon (ifn)-gamma-induced gene activity in macrophages, but the mechanism of the blockade has not been fully defined. the ifn-gamma signal transduction pathway was analyzed in leishmania donovani-infected phorbol-differentiated u937 human promonocytic cells. ifn-gamma stimulation induced marked phosphorylation of its own receptor (ifn-gammar)-alpha chain. phosphorylation of the receptor subunit was significantly inhibited after 24 h of i ... | 2000 | 10720539 |
| enhanced hematopoietic activity accompanies parasite expansion in the spleen and bone marrow of mice infected with leishmania donovani. | in this study, we have analyzed hematopoietic activity in the spleen, bone marrow, and blood of balb/c and scid mice infected with leishmania donovani. our analysis demonstrates that infection induces a rapid but transient mobilization of progenitor cells into the circulation, associated with elevated levels of granulocyte/macrophage colony-stimulating factor (gm-csf) and mip-1alpha. from 14 to 28 days postinfection, when parasite expansion begins in the spleen and bone marrow, both the frequenc ... | 2000 | 10722572 |
| nitric oxide induced expression of stress proteins in virulent and avirulent promastigotes of leishmania donovani. | intracellular survival and replication of leishmania donovani inside macrophage is essential for establishment of the disease. cytokines play an important role in this process through activation or inhibition of macrophage antimicrobial activity. nitric oxide (no) has been demonstrated to be the principal effector molecule mediating intracellular killing of leishmania. we have examined the effect of no and various other cytokines on stress protein synthesis by promastigotes of l. donovani virule ... | 2000 | 10722869 |
| altered calcium homeostasis and membrane destabilization in erythrocytes of hamsters infected with leishmania donovani. | homeostatic mechanisms regulating intracellular concentrations of ca2+ at a low level are prerequisites for maintaining the integral and cytoskeletal structure of erythrocytes under normal physiological conditions. the present study was undertaken to assess the contribution of ca2+ homeostasis in modifying red-cell stability in hamsters, during the anaemia caused by leishmania donovani. erythrocytes from the infected animals became increasingly fragile as infection progressed. this fragility may ... | 2000 | 10723523 |
| b cell-deficient mice are highly resistant to leishmania donovani infection, but develop neutrophil-mediated tissue pathology. | resolution of leishmania infection is t cell-dependent, and b lymphocytes have been considered to play a minimal role in host defense. in this study, the contribution of b lymphocytes to the response against leishmania donovani was investigated using genetically modified igm transmembrane domain (mumt) mutant mice, which lack mature b lymphocytes. when compared with wild-type mice, mumt mice cleared parasites more rapidly from the liver, and infection failed to establish in the spleen. the rapid ... | 2000 | 10725726 |
| macrophage protein kinase c: its role in modulating membrane microviscosity and superoxide in leishmanial infection. | pretreatment of macrophages with, an agonist of pkc, showed diverse effects on degradation and survival of two virulent strains of leishmania donovani promastigotes. treatment of macrophages with pma for 45 min at 37 degrees c generated significant amounts of superoxide anions and reduced the parasite burden of macrophages by up to 48 and 43% when ag83 and ge-1 strains were used for infection. staurosporine, an inhibitor of pkc, inhibited pma-dependent killing of the parasites, while tyrphostin ... | 2000 | 10731683 |
| outbreak of kala-azar in bombay. | a chance diagnosis of kala-azar in a patient referred from acworth leprosy home in bombay was followed up, resulting in an investigation of a total of 25 patients (inpatients and residents) for the presence of the disease. 30.3% of the patients investigated were found to be suffering from the disease. this confirms the earlier suspicion that bombay and especially the acworth leprosy home is an endemic area for kala-azar. | 1995 | 10740690 |
| il-12 gene-deficient c57bl/6 mice are susceptible to leishmania donovani but have diminished hepatic immunopathology. | to determine the in vivo role of il-12 in the development of protective immunity in visceral leishmaniasis caused by leishmania donovani, we examined the course of l. donovani infection in il-12-deficient c57bl/6 (il-12-/-) mice. il-12-/- mice displayed significantly higher parasite burdens in their livers and spleens than wild-type c57bl/6 mice throughout the course of infection. despite high parasite burdens, the onset of hepatosplenomegaly was significantly delayed in l. donovani-infected il- ... | 2000 | 10741399 |
| dissection of the functional domains of the leishmania surface membrane 3'-nucleotidase/nuclease, a unique member of the class i nuclease family. | class i nucleases are a family of enzymes that specifically hydrolyze single-stranded nucleic acids. recently, we characterized the gene encoding a new member of this family, the 3'-nucleotidase/nuclease (ld3'nt/nu) of the parasitic protozoan leishmania donovani. the ld3'nt/nu is unique as it is the only class i nuclease that is a cell surface membrane-anchored protein. currently, we used a homologous episomal expression system to dissect the functional domains of the ld3'nt/nu. our results show ... | 2000 | 10748102 |
| detection of antibodies to leishmania donovani in animals in a kala-azar endemic region in eastern sudan: a preliminary report. | the prevalence of antibodies against leishmania donovani in selected domestic and wild animal species in 2 villages in sudan with active l. donovani transmission in humans was investigated. screening of domestic animals (donkeys, cows, sheep, goats, camels and dogs) with the direct agglutination test (dat) detected reaction rates above the cut-off titres in donkeys (68.7%), cows (21.4%) and goats (8.5%), and which were also found in wild rats (5.5%). sera of sheep, camels and dogs had a weak agg ... | 2000 | 10748894 |
| a simple and inexpensive medium for culture of splenic aspirates in visceral leishmaniasis. | | 1999 | 10750528 |
| a comparison of the activities of three amphotericin b lipid formulations against experimental visceral and cutaneous leishmaniasis. | the polyene antibiotic, amphotericin b, the gold standard for systemic fungal infections is also a recommended second line treatment for visceral, cutaneous and mucocutaneous leishmaniasis. acute toxicity has limited the use of amphotericin b but less toxic lipid formulations, ambisome, amphocil and abelcet, have shown potential for the treatment of clinical visceral and mucocutaneous leishmaniasis. this study compares the in vitro and in vivo anti-leishmanial activity of fungizone and the three ... | 2000 | 10755238 |
| expression and subcellular localization of cpn60 protein family members in leishmania donovani. | we have identified two diverged members of the cpn60 gene family in leishmania donovani, causative agent of indian kala azar. one of the genes, cpn60.1, although actively transcribed, is not expressed to detectable levels of protein in cultured l. donovani. the other gene, cpn60.2, which, compared with cpn60.1, shows a higher sequence conservation with the hsp60 genes from trypanosoma brucei and trypanosoma cruzi is expressed constitutively in cultured promastigotes. the abundance of the gene pr ... | 2000 | 10760571 |
| short report: occurrence of leishmania donovani dna in donated blood from seroreactive brazilian blood donors. | human visceral leishmaniasis (kala-azar) transmitted by blood transfusion has been described in previous reports. seroprevalence of antibodies to leishmania donovani was shown to be related to prior blood transfusions in multiply transfused hemodialysis patients in natal, rio grande do norte, brazil. in this study, a possible correlation between seroreactivity and the presence of l. donovani dna was investigated in asymptomatic healthy blood donors. sera were tested using the fucose mannose liga ... | 2000 | 10761737 |
| membrane surface of mycobacterium microti-infected macrophages antigenically differs from that of uninfected macrophages. | identification of the antigenic changes in mycobacteria-infected macrophage may be important in understanding the mechanisms responsible for the intracellular survival of the bacteria. in the present study, mycobacterium microti-infected macrophages were utilized to investigate the possibility of differentiating the infected cells from normal cells, based on the antigenic changes occurring in the membranes. antisera were generated against bacterial extract, heat-killed bacteria and crude prepara ... | 2000 | 10767610 |
| exploitation of host cell signaling machinery: activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis. | intracellular pathogens, particularly those that target host mononuclear phagocytes, have evolved strategies to either evade or inhibit cellular mechanisms of host defense. mycobacterium tuberculosis and leishmania donovani exemplify a diverse group of microorganisms that have developed the ability to invade and replicate within host macrophages, leading to disease expression. recent studies have suggested that the pathogenesis of intracellular infection may involve interference with host cell s ... | 2000 | 10770277 |
| analysis of antisense and double stranded rna downregulation of a2 protein expression in leishmania donovani. | | 2000 | 10779609 |
| cloning of a novel inosine-guanosine transporter gene from leishmania donovani by functional rescue of a transport-deficient mutant. | purine transport is an indispensable nutritional function for protozoan parasites, since they are incapable of purine biosynthesis and must, therefore, acquire purines from the host milieu. exploiting a mutant cell line (fbd5) of leishmania donovani deficient in inosine and guanosine transport activity, the gene encoding this transporter (ldnt2) has been cloned by functional rescue of the mutant phenotype. ldnt2 encodes a polypeptide of 499 amino acids that shows substantial homology to other me ... | 2000 | 10783393 |
| an experimental vaccine providing heterologous protection for leishmania species in murine model. | five groups each of 20 balb/c mice were immunized by heat killed l. donovani promastigotes. two groups served as control. each group of mice was subdivided into 2 equal subgroups and challenged with either l. donovani or l. major. the results revealed a high cross reactivity paralleled by a high cross protection between l. donovani and l. major. heat killed l. donovani promastigotes super-passed other tested sds-page fractionated and eluted l. d. fractions identified by immune balb/c mice in pro ... | 2000 | 10786026 |
| peroxisomal targeting signal-1 receptor protein pex5 from leishmania donovani. molecular, biochemical, and immunocytochemical characterization. | the human pathogens of the leishmania and trypanosoma genera compartmentalize glycolytic and other key metabolic pathways in unique subcellular microbodies called glycosomes, organelles related to the peroxisomes of mammals and yeast. the molecular machinery that carries out the specific targeting of glycosomal proteins to the organelle has not been characterized, although the bulk of glycosomal proteins contain the cooh-terminal tripeptide glycosomal peroxisomal targeting signal-1 (pts-1) simil ... | 2000 | 10788481 |
| immunoblot analysis of the antibody response to antigens of leishmania donovani in indian kala-azar. | when infected with leishmania donovani, patients develop specific antibodies that constitute the basis of serodiagnosis. using immunoblot analysis, we examined the antibody response to antigens of l. donovani in 35 kala-azar (ka) patients and 67 controls. sera from ka patients recognised numerous antigens with molecular weights ranging from 14-110 kda. antigens of 40 kda, 55 kda, 65 kda, 70 kda and 82 kda were recognised most frequently. all ka patients produce an antibody response to one or mor ... | 1999 | 10795370 |
| kala azar. | although visceral leishmaniasis (vl) or kala-azar caused by leishmania donovani (ld) is globally, a public health problem and its eradication is of high priority, yet until now, no animal reservoir has been found in india and transmission of kala-azar occurs from man to man through the recognised vector p. argentipes. the cutaneous or dermal leishmaniasis is caused by l. tropica and this is restricted to rajasthan where it is zoonotic. investigation by sharma et al revealed the presence of zoono ... | 1999 | 10798109 |
| stage-specific development of a novel adenosine transporter in leishmania donovani amastigotes. | leishmania donovani, like all other kinetoplastida, is a purine auxotroph. comparative studies of adenosine transport in l. donovani amastigotes and promastigotes revealed that, unlike the promastigote stage, the amastigote possesses two distinct adenosine transporters (t(1) and t(2)) both with high affinities (k(m), 1.14+/-0.05 and 2. 09+/-0.13 microm, respectively). one of these transporters (t(1)) appears to be identical with the adenosine/pyrimidine nucleoside transporter of the promastigote ... | 2000 | 10802321 |
| ldarl-3a, a leishmania promastigote-specific adp-ribosylation factor-like protein, is essential for flagellum integrity. | the small g protein-encoding ldarl-3a gene, a homologue of the human arl-3 gene, was isolated from leishmania donovani, and its protein product characterised. it is unique in the leishmania genome and expressed only in the extracellular promastigote insect form, but not in the intracellular amastigote mammalian form, as shown by northern blots and western blots developed with a specific anti-c terminus immune serum. indirect immunofluorescence microscopy revealed distinct labelled spots regularl ... | 2000 | 10806117 |
| a new focus of visceral leishmaniasis in sub-himalayan (kumaon) region of northern india. | a localised focus of visceral leishmaniasis is reported for the first time from kumaon region of north india. during a period of 18 months from july 1997 to december 1998 several cases of pyrexia of unknown origin with unresponsiveness to antibiotics and anti-tubercular treatments were referred to the all india institute of medical sciences, new delhi. five of these were diagnosed to have visceral leishmaniasis. one of these was also co-infected with hiv-1. all the five cases came from an adjoin ... | 1999 | 10810593 |
| presence of a na(+)/h(+) exchanger in acidocalcisomes of leishmania donovani and their alkalization by anti-leishmanial drugs. | acidocalcisomes are acidic vacuoles present in trypanosomatids that contain most of the cellular calcium. the data presented here demonstrate that leishmania donovani acidocalcisomes possess a na(+)/h(+) exchanger. 3,5-dibutyl-4-hydroxytoluene, in the concentration range of 0-20 microm, inhibited the na(+)/h(+) exchanger, and strongly stimulated the activity of the vacuolar h(+)-atpase responsible for vacuolar acidification. as occurs with na(+), the cationic anti-leishmanial drugs pentamidine, ... | 2000 | 10812075 |
| putative p-glycoprotein expression in arsenite-resistant leishmania donovani down-regulated by verapamil. | western immunoblots of whole cell lysate and crude membrane extract of an in vitro selected sodium m-arsenite-resistant l. donovani strain revealed a 230-kda protein identified by an anti-p-glycoprotein (pgp) antibody. immunofluorescence microscopy, using the same antibody, detected putative pgp on resistant parasites. overexpression of the putative pgp was down-regulated by verapamil. these results provided, possibly, the first evidence that (i) overexpression of pgp-like protein occurs in arse ... | 2000 | 10814510 |
| bronchopulmonary and mediastinal leishmaniasis: an unusual clinical presentation of leishmania donovani infection. | we describe a case of unusual leishmaniasis in a sudanese man with a history of progressively enlarging granulomatous mediastinal lymphadenopathy, worsening hemoptysis, and an intense mucosal granulomatous inflammatory response in the large bronchi. leishmania donovani dna was detected in bronchial biopsies by polymerase chain reaction. this is a novel description of human leishmanial infection in an immunocompetent patient involving this anatomical site. the patient's condition improved clinica ... | 2000 | 10816146 |
| activity of the novel immunomodulatory compound tucaresol against experimental visceral leishmaniasis. | tucaresol, a novel immunomodulator, was inactive against leishmania donovani amastigotes in both peritoneal and bone marrow macrophages in vitro at concentrations between 100 and 1 microm, with toxicity to macrophages and parasites at 300 microm. however, against l. donovani in balb/c mice at doses between 80 and 1.25 mg/kg of body weight administered once daily by the oral route during days 7 to 11 of infection, an optimal dose of 5 mg/kg produced a 43.8 to 62.4% suppression of liver amastigote ... | 2000 | 10817698 |
| antileishmanial activities of stearylamine-bearing liposomes. | here we report the activity of liposomes comprising egg phosphatidylcholine (pc) and stearylamine (sa) against leishmania donovani parasites. both promastigotes and intracellular amastigotes in vitro and in vivo were susceptible to sa-pc liposomes. a single dose of 55 mg of sa-pc liposomes/animal could significantly reduce the hepatic parasite burden by 85 and 68% against recent and established experimental visceral leishmaniasis, respectively, suggesting their strong therapeutic potential. | 2000 | 10817745 |
| structure-activity study on the in vitro antiprotozoal activity of glutathione derivatives. | a series of n-, s-, and cooh-blocked glutathione derivatives were evaluated against the pathogenic parasites trypanosoma brucei, trypanosoma cruzi, and leishmania donovani in vitro, to identify the determinants necessary for activity and for further development into an active lead structure. the results show that n,s-blocked glutathione diesters are the most effective inhibitors of t. brucei with structures 14-16 being the most active, 14 having an ic(50) approximately 1.9 microm. the toxicity e ... | 2000 | 10821719 |
| interleukin 1alpha activity of peritoneal and bone marrow macrophages infected with leishmania major and leishmania donovani in vitro. | in this study, the pattern of interleukin-1alpha (il-1alpha) production by both peritoneal (pm) and bone marrow macrophages (bmm) from resistant (c3h/hej) and susceptible (balb/c) mice was investigated, using a bioassay and an il-1alpha-specific elisa kit. pm from normal uninfected mice showed either an initial high (c3h/hej) or a neglected (balb/c) level of il-1alpha activity, respectively, probably due to thioglycollate stimulation. infection with leishmania major induced only a marginal effec ... | 2000 | 10831379 |
| pathogenic leishmania secrete antigenically related chitinases which are encoded by a highly conserved gene locus. | recently, we identified and characterized a single-copy chitinase gene (ldcht1) from leishmania donovani, a protozoan pathogen of humans. it has been hypothesized that this parasite enzyme plays a critical role in the survival of all leishmania species within their sandfly vectors and for their transmission to humans. thus, in the current study, pulse-field gel electrophoresis and southern hybridization with the ldcht1 gene probe were used to demonstrate that this chitinase gene has been conserv ... | 2000 | 10831391 |
| cloning and characterization of leishmania donovani telomeres. | we describe here the cloning and sequence characterization of the absolute termini of several telomeres from the human parasite leishmania donovani using a vector-adapter protocol. the 3' protruding strand of l. donovani telomeres terminates with the sequence 5'-ggttagggt-oh 3'. this single-stranded sequence is adjacent to tandemly repeated blocks of double-stranded sequence consisting of variable numbers of the hexameric repeat 5'-tagggt-3', variable numbers of an octameric repeat 5'-tggtcatg-3 ... | 2000 | 10831393 |
| development of an immunoenzymatic assay for the detection of human antibodies against trypanosoma cruzi calreticulin, an immunodominant antigen. | we have developed an indirect immunoenzymatic assay (elisa) for the detection of human antibodies against calreticulin (formerly known as tc45), a dimorphic trypanosoma cruzi antigen, described in our laboratory. pvc microtitration plates were sensitized with the monoclonal anti-calreticulin antibody (moab) and reacted with calreticulin present in a partially purified preparation. the presence of anti-t. cruzi calreticulin igg in sera from infected individuals was tested. the data generated with ... | 2000 | 10838212 |
| blasticidin resistance: a new independent marker for stable transfection of leishmania. | | 2000 | 10838227 |
| the length of the combined 3' untranslated region and poly(a) tail does not control rates of glyceraldehyde-3-phosphate dehydrogenase mrna translation in three species of parasitic protists. | experimental observations suggested that the length of the glyceraldehyde-3-phosphate dehydrogenase (gapdh) mrna 3' end has a role in regulating rates of translation in the parasitic protists trypanosoma brucei, leishmania donovani, and trichomonas vaginalis. using a pcr assay for poly(a) tail length, we measured the size of the rna 3' end under different growth conditions in all three species. our results showed that the combined 3' untranslated region and poly(a) tail of gapdh mrna do not vary ... | 2000 | 10852893 |
| hiv-1 alters t helper cytokines, interleukin-12 and interleukin-18 responses to the protozoan parasite leishmania donovani. | to investigate the in vitro and in vivo effect of hiv-1 on lymphoproliferative and t helper (th) cytokine responses in leishmaniasis. | 2000 | 10853973 |
| hunters hounded as leishmaniasis is diagnosed in foxhounds. | | 2000 | 10863579 |
| synthesis and evaluation of 9,9-dimethylxanthene tricyclics against trypanothione reductase, trypanosoma brucei, trypanosoma cruzi and leishmania donovani. | derivatives of 9,9-dimethylxanthene were synthesised and evaluated against trypanothione reductase (tr) and in vitro against parasitic trypanosomes and leishmania. high in vitro antiparasitic activity was observed for some derivatives with one compound showing high activity against all three parasites (ed50 values of 0.02, 0.48 and 0.32 microm, for trypanosoma brucei, trypanosoma cruzi, and leishmania donovani, respectively). the lack of correlation between inhibitory activity against tr and ed5 ... | 2000 | 10866368 |
| squalamine analogues as potential anti-trypanosomal and anti-leishmanial compounds. | this paper concerns the synthesis of various simplified analogues of the novel anti-microbial agent, squalamine. the compounds were then investigated for activity against trypanosoma brucei, the causative agent of african trypanosomiasis, trypanosoma cruzi, the causative agent of chagas disease and leishmania donovani, the causative agent of visceral leishmaniasis. several compounds showed in vitro activity, especially against t. brucei and l. donovani. however, one compound showed poor in vivo ... | 2000 | 10866389 |
| visceral leishmaniasis and other severe infections in an adult patient with p47-phox-deficient chronic granulomatous disease. | we report a rare case of a male patient without known immunodeficiency consecutively diagnosed with visceral leishmaniasis, brain abscess and cavitating pneumonia in the 3rd decade of life. chronic granulomatous disease (cgd) was diagnosed by a nitroblue tetrazolium test. a p47-phox mutation of the nadph oxidase of the leukocytes was suspected by immunoblotting and confirmed by dna analysis. the patient was homozygous for this mutation while his mother and sister were heterozygous asymptomatic c ... | 2000 | 10879644 |
| novel methods for the encapsulation of meglumine antimoniate into liposomes. | the antimonial drug, meglumine antimoniate, was successfully encapsulated in dehydration-rehydration vesicles and in freeze-dried empty liposomes (fdels). high encapsulation efficiencies (from 28 to 58%) and low weight ratios of lipids to encapsulated antimony (from 1:0.15 to 1:0.3) were achieved. these formulations, contrary to those obtained by conventional methods, can be stored as intermediate lyophilized forms and reconstituted just before use. the efficacy of fdel-encapsulated meglumine an ... | 2000 | 10881061 |
| characterisation of bangladeshi leishmania isolated from kala-azar patients by isoenzyme electrophoresis. | to identify the prevalent leishmania species in bangladesh, a total of nine patients aged 4-35 years, were studied; six (66.7%) of them were below 20 years of age. all the patients were clinically diagnosed to have visceral leishmaniasis; their haematological profile was in accordance with leishmaniasis and all were improved after treatment with sodium stibogluconate. all the aspirated materials (eight bone marrows and one splenic aspirate) yielded growth of leishmania parasite in nnn media; lei ... | 2000 | 10882903 |
| in vivo antileishmanial action of ir-(cod)-pentamidine tetraphenylborate on leishmania donovani and leishmania major mouse models. | ir-(cod)-pentamidine tetraphenylborate which has previously been studied on promastigote forms of leishmania, was investigated for its antileishmanial properties compared with pentamidine used as reference compound. in vitro, the iridium complex had the same ic50 value on intracellular forms of leishmania as pentamidine (15 microm). in vivo, the compound could not be injected intravenously due to the dmso excipient so that the treatments were performed intraperitoneally or subcutaneously. on the ... | 2000 | 10887656 |
| visceral leishmaniasis in sudan: first identifications of leishmania from dogs. | | 2000 | 10897352 |
| evaluation of a 200-kda amastigote-specific antigen of l. donovani by enzyme-linked immunosorbent assay (elisa) for the diagnosis of visceral leishmaniasis. | a purified 200-kda antigenic fraction from leishmania donovani axenic amastigotes was evaluated by elisa for the detection of antibody response in visceral leishmaniasis (vl) patients, post kala-azar dermal leishmaniasis (pkdl) patients and controls, for the diagnosis of visceral leishmaniasis. a positive antibody response to the 200-kda amastigote fraction and to leishmania amastigote soluble antigen (lasa) was found in 29 (96.6%) and 30 ((100%) confirmed vl patients, respectively, by the use o ... | 2000 | 10897360 |
| in vitro reversion of amphotericin b resistance in leishmania donovani by poloxamer 188. | a micellar formulation of amphotericin b (amb) solubilized with poloxamer 188 was evaluated against an amb leishmania donovani-resistant line. a concave isobologram showed a synergistic effect of this association against promastigotes. this result was confirmed with amastigotes since the 50% effective concentration of the new formulation was 100 times less than that of the control amb formulation. | 2000 | 10898700 |
| cases of kala-azar without any hepatosplenomegaly. | | 2000 | 10902492 |
| bioactive compounds from celaenodendron mexicanum. | bioactivity-directed fractionation of the chcl3-meoh extract of the leaves of celaenodendron mexicanum by means of the brine shrimp lethality test and chromatographic techniques led to the isolation of three carboxylic acid triterpenes, the new tirucalla-type triterpene, 3 alpha-hydroxytirucalla-7,24z-dien-26-oic acid, 3-oxotirucalla-7,24z-dien-26-oic acid, and epi-oleanolic acid, and three biflavonoids amentoflavone, podocarpusflavone a, and podocarpusflavone b. four non-active compounds friede ... | 2000 | 10909269 |
| oxoaporphine alkaloids and quinones from stephania dinklagei and evaluation of their antiprotozoal activities. | bioactivity-guided fractionation of stephania dinklagei yielded six compounds including, two zwitterionic oxoaporphine alkaloids, n-methylliriodendronine, and 2-o,n-dimethylliriodendronine, two oxoaporphine alkaloids, liriodenine, and dicentrinone, one aporphine alkaloid, corydine, and one anthraquinone, aloe-emodin. apart from corydine, the isolates have not been reported as constituents of s. dinklagei. n-methylliriodendronine, and 2-o,n-dimethylliriodendronine are reported for the first time ... | 2000 | 10909274 |
| inhibitory and lytic effects of phenothiazine derivatives and related tricyclic neuroleptic compounds, on entamoeba histolytica hk9 and hm1 trophozoites. | it has been shown previously that tricyclic neuroleptics like clomipramine and chlorpromazine have lethal effects on leishmania donovani and l. major, and other studies indicate that the phenothiazine inhibitors of trypanothione reductase are potential anti-trypanosomal and anti-leishmanial drugs. with this in mind and our original observation on the presence of trypanothione in entamoeba histolytica hk9, we examined the possible inhibitory effects of various phenothiazine and tricyclic derivati ... | 2000 | 10918039 |
| putrescine and spermidine transport in leishmania. | the transport of putrescine and spermidine into leishmnania donovani promastigotes and leishmania mexicana promastigotes and amastigotes has been characterised. polyamine transport was shown to be saturable and temperature-sensitive for both developmental stages of leishmania. transport was ph-dependent with ph optima of 7.4 and 5.5 for promastigotes and amastigotes, respectively. the uptake process was independent of extracellular na+, but inhibited by protonophores and h+-atpase inhibitors. ki ... | 2000 | 10924755 |
| expression of the am gene locus in infective stages of leishmania. | | 2000 | 10924759 |
| inhibition of glutathione synthesis as a chemotherapeutic strategy for leishmaniasis. | this study focuses on the use of buthionine sulphoximine (bso), a gamma-glutamylcysteine synthetase inhibitor, on leishmania donovani growth. the effect of bso on amastigote multiplication within macrophages showed that 5 mm bso decreased infectivity by about 50% and the mean number of amastigotes per 100 infected macrophages by 21%. the mechanism may be that bso resulted in enhanced nitric oxide (no) levels within macrophages, probably due to inhibition of gsh content since gsh (10 mm) given af ... | 2000 | 10929144 |
| susceptible hosts: a resort for parasites right in the eye of the immune response. | trypanosomatid protozoan parasites express an aggressive strategy of parasitism by infecting host macrophages and inducing extensive t-lymphocyte activation. one goal of such strategy is to drive the immune response of genetically susceptible hosts to a state of unresponsiveness regarding parasite killing. unresponsiveness is achieved through different mechanisms, depending on the parasite species. in this brief review, recent findings on the molecular and cellular bases of the parasites' exploi ... | 2000 | 10932108 |
| in vitro leishmanicidal activity of monomeric and dimeric naphthoquinones. | a series of monomeric and dimeric naphthoquinones with potential for treatment of leishmania infections was identified in vitro using both a direct cytotoxicity assay against extracellular promastigotes of leishmania donovani, leishmania infanturn, leishmania enriettii, and leishmania major and a test against intracellular amastigote l. donovani residing within murine macrophages. several naphthoquinones proved to be active at concentrations in the microgram range (ec(50) 0.9-17.0 microg/ml). wh ... | 2000 | 10936572 |
| leishmania donovani in blood smears of asymptomatic persons. | leishmania amastigotes have been detected in the peripheral blood smears of indian kala-azar patients mostly during night. it was, therefore, thought worthwhile to find out whether such amastigotes could be shown in healthy subjects who did not have any symptoms by history or signs on clinical examination. leishmania-stained blood smears of 450 asymptomatic healthy individuals residing in an endemic village in bihar (india) were examined by oil-immersion microscopy for the detection of amastigot ... | 2000 | 10936579 |
| effects of elevated temperature and lower ph on infectivity of leishmania donovani promastigotes. | | 1999 | 10937304 |
| ld body-negative bone marrow cases of kala-azar in dharan, nepal. | | 1999 | 10937305 |
| leishmania donovani promastigotes evade the activation of mitogen-activated protein kinases p38, c-jun n-terminal kinase, and extracellular signal-regulated kinase-1/2 during infection of naive macrophages. | the protozoan parasite leishmania fails to activate naive macrophages for proinflammatory cytokines production, and selectively impairs signal transduction pathways in infected macrophages. because mitogen-activated protein kinases (mapk)- and nf-kappab-dependent signaling pathways regulate proinflammatory cytokines release, we investigated their activation in mouse bone marrow-derived macrophages (bmm) exposed to leishmania donovani promastigotes. in naive bmm, the parasite failed to induce the ... | 2000 | 10940915 |
| ligation of fc receptor of macrophages stimulates protein kinase c and anti-leishmanial activity. | fc receptors are known to express on the surface of mature monocytes, macrophages and lymphocytes. in this study a ligand e.g. liposomal igg (human igg coupled to pe-liposome via carbodimide reaction) was developed to ligate the fc receptor of macrophages. when liposomal igg was incubated with macrophages at 37 degrees c for 5 min, it induced the macrophage activation which suppress the parasite burden approximately to an extent of 60%, 50% and 45%, when macrophages were infected with ur6, ag83 ... | 2000 | 10942195 |
| ril-2-stimulated splenocytes reactivate the no2-producing ability of macrophages infected by leishmania donovani. | infection with l. donovani down-regulates immunity and parasite clearance by macrophages. treatment with il-2-stimulated-splenocytes activate parasiticidal action in vitro in peritoneal macrophages of c57bl/6 (lsh(s)) mice and also was effective in stimulating infected macrophages to produce no2-. | 2000 | 10946826 |
| arsenite-resistant leishmania donovani promastigotes express an enhanced membrane p-type adenosine triphosphatase activity that is sensitive to verapamil treatment. | an arsenite-resistant strain of leishmania donovani was generated in vitro by sequential exposure to higher concentrations of sodium m-arsenite. the resistant strain displayed a low level of cross-resistance to structurally unrelated drugs such as doxorubicin and pentamidine. this cross-resistance was sensitive to the calcium-channel blocker verapamil. the membrane-associated p-type adenosine triphosphatase (atpase) activity detected in crude membrane fractions of the resistant strain was 3-fold ... | 2000 | 10952266 |
| preformed membrane-associated stores of interleukin (il)-12 are a previously unrecognized source of bioactive il-12 that is mobilized within minutes of contact with an intracellular parasite. | the prevailing paradigm is that production of the interleukin (il)-12 p70 heterodimer, a critical t helper cell type 1 (th1)-inducing cytokine, depends on the induced transcription of the p40 subunit. concordant with this paradigm, we found that dendritic cells (dcs) produced il-12 p70 only after at least 2-4 h of stimulation with lipopolysaccharide plus interferon gamma. however, using several complementary experimental approaches, including electron and confocal microscopy, we now show that re ... | 2000 | 10952720 |
| use of an additional hydrophobic binding site, the z site, in the rational drug design of a new class of stronger trypanothione reductase inhibitor, quaternary alkylammonium phenothiazines. | improved rationally designed lead drug structures against african trypanosomiasis, chagas disease, and leishmaniasis were obtained against trypanothione reductase from trypanosoma cruzi. substituted-benzyl [3-(2-chloro-4a, 10a-dihydrophenothiazin-10-yl)propyl]dimethylammonium salts, synthesized by menschutkin quaternization of the tertiary alkylamine omega-nitrogen atom of chlorpromazine, were linear, competitive inhibitors of recombinant trypanothione reductase from t. cruzi, with either trypan ... | 2000 | 10956223 |
| induction of partial protection against leishmania donovani by promastigote antigens in negatively charged liposomes. | negatively charged liposomes, proposed as potential vaccine adjuvants, have been extensively studied in association with various antigens. in the present study, we investigated the adjuvanicity of negatively charged liposomes to enhance the protective immunity of membrane antigens of leishmania donovani promastigotes (lag). in comparison to the control mice immunized with phosphate-buffered saline and empty liposomes, immunization with free lag led to significant levels of protection against inf ... | 2000 | 10958448 |
| sequencing a specific kinetoplast dna fragment of leishmania donovani for polymerase chain reaction amplification in diagnosis of leishmaniasis in bone marrow and blood samples. | a set of oligonucleotide primers i and ii was developed by analyzing the specificity of a cloned kinetoplast dna (kdna) fragment of leishmania donovani and sequencing the fragment. polymerase chain reaction (pcr) was conducted with the primers to amplify a minicircle kdna fragment (297 bp) to detect l. donovani in the bone marrow (22 samples), whole blood (16 samples), and serum (17 samples) of 22 patients with visceral leishmaniasis. all of 22 patients were diagnosed by microscopic identificati ... | 2000 | 10958464 |
| small-scale isolation of high molecular weight dna from leishmania braziliensis. | in this paper, we report a method for isolation of high molecular weight dna from leishmania promastigotes. this technique is especially indicated for small-scale purification of dna suitable for the construction of highly representative genomic libraries. in our protocol, lysis buffer is compatible with rnase treatment, avoiding an additional precipitation step and consequent shearing of dna. in order to prove the quality of the dna isolated by this method, a leishmania braziliensis genomic lib ... | 2000 | 10958468 |
| the immunologically protective p-4 antigen of leishmania amastigotes. a developmentally regulated single strand-specific nuclease associated with the endoplasmic reticulum. | the purified membrane-associated leishmania pifanoi amastigote protein p-4 has been shown to induce protective immunity against infection and to elicit preferentially a t helper 1-like response in peripheral blood mononuclear cells of patients with american cutaneous leishmaniasis. as this molecule is potentially important for future vaccine studies, the l. pifanoi gene encoding the p-4 membrane protein was cloned and sequenced. southern blot analyses indicate the presence of six tandemly arraye ... | 2000 | 10969068 |
| luteolin, an abundant dietary component is a potent anti-leishmanial agent that acts by inducing topoisomerase ii-mediated kinetoplast dna cleavage leading to apoptosis. | plant-derived flavonoids, which occur abundantly in our daily dietary intake, possess antitumor, antibacterial, and free radical scavenging properties. they form active constituents of a number of herbal and traditional medicines. several flavonoids have been shown to exert their action by interacting with dna topoisomerases and promoting site-specific dna cleavage. therefore, flavonoids are potential candidates in drug design. we report here that, although the flavonoids luteolin and quercetin ... | 2000 | 10972088 |
| analysis of stereoelectronic properties of camptothecin analogues in relation to biological activity. | camptothecin and four of its 10,11-methylenedioxy analogues were examined for their activity against the pathogenic protozoan leishmania donovani in vitro. the methylenedioxy analogues were 36- to 180-fold more potent than the parent camptothecin, possessing ic50 values ranging from 160 to 32 nm against the parasite. our finding that the methylenedioxy camptothecins possess greater activity than camptothecin, which is also the case for other cell types and for the generation of cleavable complex ... | 2000 | 10976522 |
| mutations in a trna import signal define distinct receptors at the two membranes of leishmania mitochondria. | nucleus-encoded trnas are selectively imported into the mitochondrion of leishmania, a kinetoplastid protozoan. an oligoribonucleotide constituting the d stem-loop import signal of trna(tyr)(gua) was efficiently transported into the mitochondrial matrix in organello as well as in vivo. transfer through the inner membrane could be uncoupled from that through the outer membrane and was resistant to antibody against the outer membrane receptor tab. a number of mutations in the import signal had dif ... | 2000 | 10982857 |
| screening sandflies for natural infection with leishmania donovani, using a non-radioactive probe based on the total dna of the parasite. | digoxigenin-labelled total, leishmania donovani dna was used as a probe to detect the parasite in indian phlebotomus argentipes. the probe was quite sensitive, detecting as little as 0.3 pg parasite dna, equivalent to approximately 100 parasites. positive signals could be detected in 12 (32%) of the 38 small (two- to 30-fly) pools of the wild-caught p. argentipes investigated and in a pool of 10 laboratory-bred p. argentipes fed on a patient with post-kala-azar dermal leishmaniasis. none of the ... | 2000 | 10983557 |
| rab5 regulates the kiss and run fusion between phagosomes and endosomes and the acquisition of phagosome leishmanicidal properties in raw 264.7 macrophages. | phagolysosome biogenesis is essential for the killing and degradation of intracellular pathogens. it involves the fusion of phagosomes with various endocytic organelles, a process known to be regulated in part by rab proteins. we generated raw 264.7 macrophages expressing an active mutant of rab5 (rab5(q79l)) to determine the role of rab5 in phagocytosis and phagolysosome biogenesis. our results indicate that rab5 stimulates phagocytosis of latex beads but not fc or c3 receptor-mediated phagocyt ... | 2000 | 10984443 |
| identification of vaccine candidates for experimental visceral leishmaniasis by immunization with sequential fractions of a cdna expression library. | visceral leishmaniasis caused by the intracellular parasite leishmania donovani is a significant public health problem in many regions of the world. because of its large genome and complex biology, developing a vaccine for this pathogen has proved to be a challenging task and, to date, protective recombinant vaccine candidates have not been identified. to tackle this difficult problem, we adopted a reductionist approach with the intention of identifying cdna sequences in an l. donovani amastigot ... | 2000 | 10992459 |
| oral miltefosine in the treatment of kala-azar. | | 2000 | 11002688 |
| therapy of visceral leishmaniasis in renal transplant recipients intolerant to pentavalent antimonials. | visceral leishmaniasis should be suspected in renal transplant recipients in whom a fever develops of unknown origin. a 53-year-old renal transplant recipient developed pyrexia, hepatosplenomegaly, and pancytopenia 4 years after transplantation. antileishmaniasis serology was negative, and the diagnosis was confirmed through bone marrow examination. treatment with glucantine (n-methylglucamine antimoniate) led to acute pancreatitis, and treatment with ketoconazole plus allopurinol for 21 days wa ... | 2000 | 11003361 |
| the effects of clofazimine, niclosamide & amphotericin b, on electron transport of leishmania donovani promastigotes. | the study was undertaken to explore the locus of interaction of clofazimine and niclosamide which showed substantial growth inhibition property in leishmania donovani promastigotes. | 2000 | 11006656 |
| interleukin-12 regulates the response to chemotherapy in experimental visceral leishmaniasis. | in experimental visceral leishmaniasis, interleukin (il)-12 initiates control over leishmania donovani via th1 cell activation, interferon (ifn)-gamma secretion, and granuloma formation. because the leishmanicidal effect of conventional therapy, pentavalent antimony (sb), also requires t cells and endogenous ifn-gamma, we tested il-12 as a determinant of host responsiveness to chemotherapy. l. donovani-challenged il-12p35 gene knockout (ko) mice permitted uncontrolled hepatic infection and faile ... | 2000 | 11023473 |
| immunization with recombinant ld1 antigens protects against experimental leishmaniasis. | the genes, orff and bt1 (previously orfg), are part of the multigenic ld1 locus on chromosome 35 which is frequently amplified in leishmania. bt1 encodes a biopterin transporter, while the function of the orff gene product is unknown, but it is localized to the nucleus. we show here that immunization of mice with recombinant orff and bt1 proteins, individually, or in combination, conferred partial protection against challenge with leishmania donovani. protection correlated with the production of ... | 2000 | 11027804 |
| biochemical and ultrastructural alterations caused by newly synthesized 1,2,4-triazole[1,5a]pyrimidine derivatives against phytomonas staheli (trypanosomatidae). | six compounds, all newly synthesized triazole-pyrimidine derivatives that proved inhibitory of in in vitro growth of epimastigotes in trypanosoma cruzi and of promastigotes of leishmania donovani and phytomonas staheli, were studied to investigate their toxic effects. as a biological model, the plant trypanosome p. staheli, which causes sudden wilt in the oil palm and hartrot in the coconut palm, was used. the six compounds markedly inhibited macromolecule synthesis (nucleic acids and proteins) ... | 2000 | 11031318 |
| cyclooxygenase-2 expression in macrophages: modulation by protein kinase c-alpha. | cyclooxygenase-2 (cox-2) is an inducible enzyme responsible for high levels of pg production during inflammation and immune responses. previous studies with pharmacological inhibitors suggested a role for protein kinase c (pkc) in pg production possibly by regulating cox-2 expression. in this study, we addressed the role of pkc-alpha in the modulation of cox-2 expression and pge2 synthesis by the overexpressing of a dominant-negative (dn) mutant of this isoenzyme in the mouse macrophage cell lin ... | 2000 | 11034408 |