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Leishmania Major (leishmania + major)
Terms modified by Leishmania Major Selected AbstractsEvidence for a sliding-resistance at the tip of the trypanosome flagellumCYTOSKELETON, Issue 12 2006David Woolley Abstract Motility in trypanosomes is achieved through the undulating behaviour of a single "9 + 2" flagellum; normally the flagellar waves begin at the flagellar tip and propagate towards the base. For flagella in general, however, propagation is from base-to-tip and it is believed that bend formation, and sustained regular oscillation, depend upon a localised resistance to inter-doublet sliding - which is normally conferred by structures at the flagellar base, typically the basal body. We therefore predicted that in trypanosomes there must be a resistive structure at the flagellar tip. Electron micrographs of Crithidia deanei, Herpetomonas megaseliae, Trypanosoma brucei and Leishmania major have confirmed that such attachments are present. Thus, it can be assumed that in trypanosomes microtubule sliding at the flagellar tip is resisted sufficiently to permit bend formation. Cell Motil. Cytoskeleton 2006. © 2006 Wiley-Liss, Inc. [source] Notch1 expression on T,cells is not required for CD4+ T,helper differentiationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2004Fabienne Tacchini-Cottier Abstract Notch1 proteins are involved in binary cell fate decisions. To determine the role of Notch1 in the differentiation of CD4+ Th1 versus Th2 cells, we have compared T,helper polarization in vitro in naive CD4+ T,cells isolated from mice in which the N1 gene is specifically inactivated in all mature T,cells. Following activation, Notch1-deficient CD4+ T,cells transcribed and secreted IFN-, under Th1 conditions and IL-4 under Th2 conditions at levels similar to that of control CD4+ T,cells. These results show that Notch1 is dispensable for the development of Th1 and Th2 phenotypes in vitro. The requirement for Notch1 in Th1 differentiation in vivo was analyzed following inoculation of Leishmania major in mice with a T,cell-specific inactivation of the Notch1 gene. Following infection, these mice controlled parasite growth at the site of infection and healed their lesions. The mice developed a protective Th1 immune response characterized by high levels of IFN-, mRNA and protein and low levels of IL-4 mRNA with no IL-4 protein in their lymph node cells. Taken together, these results indicate that Notch1 is not critically involved in CD4+ T,helper,1 differentiation and in resolution of lesions following infection with L.,major. [source] Efficacy of glucantime in the treatment of Old World cutaneous leishmaniasisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2009Rukhsana Firdous MPhil Background, Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. Depending on the parasite species and host response, the disease presents itself in different clinical forms. The cutaneous form of the disease is most common in the Old World. Pentavalent antimonials in the form of an injection represent the most widely used therapy for all clinical forms of the disease. As a result of reports on the development of resistance from various parts of the world, we thought it pertinent to determine its response in our region. Methods, Two hundred and seven military personnel with cutaneous leishmaniasis, caused by Leishmania major, were treated with glucantime according to the World Health Organization (WHO) recommended protocol. All patients were nonindigenous to the area and had moved from a nonendemic area to a highly endemic area. Results, Thirty-seven per cent of patients were cured within 15 days. The cure percentage reached 81% when 20 mg/kg/day was continued to 20 days. Twenty-five patients who failed to respond were subjected to a further course of glucantime injection. Sixteen responded by the 10th day of treatment, and the remaining nine were cured by completion of the second course, i.e. within 40 days. The drug was administered intramuscularly. The common side-effects noted were vertigo, headache, anorexia, temperature, and joint pain. Conclusion, Glucantime is still effective against Old World cutaneous leishmaniasis when used in the doses recommended by WHO. [source] Phlebotomus (Adlerius) halepensis vector competence for Leishmania major and Le. tropicaMEDICAL AND VETERINARY ENTOMOLOGY, Issue 3 2003J. Sádlová Abstract., In Eurasia, phlebotomine sandflies of the subgenus Adlerius (Diptera: Psychodidae) comprise about 20 known species. Some are suspected vectors of visceral leishmaniasis (VL) and at least one species has been implicated as a vector of cutaneous leishmaniasis (CL). We tested Phlebotomus (Adlerius) halepensis Theodor (Jordan strain) for CL vector competence, compared with three standard vectors: Phlebotomus (Phlebotomus) duboscqi N-L. from Senegal, Phlebotomus (Paraphlebotomus) sergenti Parrot from Turkey and the Neotropical Lutzomyia longipalpis (L. & N) (Jacobina strain). Sandfly females were membrane-fed on amastigote suspensions of Leishmania major Y. & S. and Le. tropica (Wright) (Kinetoplastida: Trypanosomatidae) and examined for parasite development 3, 6 and 10 days post-infection. Phlebotomus halepensis showed high susceptibility to both leishmanias, supporting typical suprapylarian parasite development similar to the other vectors. Phlebotomus halepensis infection rates were ,90% for Le. major and ,80% for Le. tropica, with high parasite densities. Development of infections was relatively fast, colonizing the thoracic midgut by 6 days post-bloodmeal in every case and reaching the stomodeal valve in >80% of flies. In late-stage infections, 10 days post-bloodmeal, nearly all P. halepensis females had cardia and stomodeal valve filled with very high numbers of parasites and some Le. tropica -infected females had promastigotes in the pharynx and proboscis. Host choice experiments in the laboratory showed that P. halepensis females fed readily on rat or rabbit and preferred the human forearm. In view of its vector competence and partial anthropophily, we infer that P. halepensis is a potential vector of cutaneous as well as visceral leishmaniases. [source] Rhesus monkey model for Leishmania major transmitted by Phlebotomus papatasi sandfly bitesMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2001R. J. Probst Summary Leishmaniasis research needs a near-human model for investigations of natural infection processes, immunological responses and evaluation of treatments. Therefore, we developed a reproducible system using Leishmania major Yakimoff & Schokhor (Trypanosomatidae: Kinetoplastida), the cause of Old World zoonotic cutaneous leishmaniasis (ZCL), transmitted to rhesus monkeys Macaca mulatta (Zimmerman) (Primates: Cercopithecidae) by sandfly bites of experimentally infected Phlebotomus papatasi (Scopoli) (Diptera: Psychodidae). Eight monkeys of presumed Indian origin (Leishmania naïve) were exposed to bites of female sandflies that had been infected with L. major by membrane-feeding on human blood seeded with amastigotes isolated from hamster footpad lesions. Infection rates of membrane-fed sandflies averaged >,85% seven days after the infective feed, with uniformly high numbers of promastigotes in the stomodaeal valve region of the sandfly gut. Nodules and ulcerating dermal lesions developed on 7/8 monkeys 2,4 weeks post-bite and persisted for 3,7 months. Monkeys also developed satellite lesions beyond the area of sandfly bites on the head, but not on the chest. Three re-challenged monkeys developed lesions that healed faster than lesions from their primary challenges. After infection, monkeys developed delayed type hypersensitivity (DTH) responses to a panel of Leishmania skin test antigens (LSTA) and, when tested by ELISA and IFA, showed significant post-infection antibody titres which typically rose for ,170 days and then gradually receded during the next 100 days following the first challenge. After the second challenge, antibody titres spiked higher within ,50 days and receded more rapidly. In contrast, four rhesus macaques of Chinese origin developed no lesions following infected sandfly bites, although they raised antibodies and LSTA reactions, indicating subclinical infection. [source] Glycosomes: parasites and the divergence of peroxisomal purposeMOLECULAR MICROBIOLOGY, Issue 3 2004Marilyn Parsons Summary Peroxisomes are membrane-bounded organelles that compartmentalize a variety of metabolic functions. Perhaps the most divergent peroxisomes known are the glycosomes of trypanosomes and their relatives. The glycolytic pathway of these organisms resides within the glycosome. The development of robust molecular genetic and proteomic approaches coupled with the completion of the genome sequence of the pathogens Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major provides an opportunity to determine the complement of proteins within the glycosome and the function of compartmentation. Studies now suggest that regulation of glycolysis is a strong driving force for maintenance of the glycosome. [source] Characterization of the A2,A2rel gene cluster in Leishmania donovani: involvement of A2 in visceralization during infectionMOLECULAR MICROBIOLOGY, Issue 4 2001Wen-Wei Zhang The A2 gene family is present in Leishmania donovani, which causes fatal visceral leishmaniasis in human patients, but is not present in Leishmania major, which causes cutaneous leishmaniasis infections. The A2 genes in L. donovani are stage specific and are expressed at high levels in the amastigote stage in the mammalian host, but are not expressed in the promastigote stage in the insect sandfly vector. The A2 genes are tandem repeated with a distinct gene family termed the A2rel genes. In order to characterize the structure and function of the A2,A2rel gene clusters, the 5, and 3, DNA sequences flanking the A2,A2rel cluster were isolated, sequenced and used to generate mutants through gene targeting. Although it was possible to generate partial A2,A2rel gene clusters knock-out mutants, it was not possible to delete all the A2,A2rel gene clusters completely from the L. donovani genome, suggesting that, within this cluster, there are genes that are essential for survival in culture. Characterization of these mutants revealed that A2 and A2rel gene expression was compensated by amplifying the remaining intact A2 and A2rel genes, and the proliferation of these mutants in culture and their virulence in BALB/c mice were compromised. In order to explore further the biological role of A2, the L. donovani A2 gene was introduced into L. major. In comparison with the control L. major, the A2-expressing L. major parasites demonstrated an increased ability to survive in the spleen of BALB/c mice. These data suggest that A2 plays a role in the visceralization of infection associated with L. donovani. [source] Differential in vitro CD4+/CD8+ T-cell response to live vs. killed Leishmania majorPARASITE IMMUNOLOGY, Issue 2 2010M. NATEGHI ROSTAMI Summary Clinical trials of killed Leishmania vaccines showed a limited efficacy compared with leishmanization (LZ). The reason for this difference in protection against cutaneous leishmaniasis (CL) is not known and in vivo studies on T-cell function may provide valuable information. Nevertheless, there are limited studies on the nature of the stimulatory effects of live vs. killed parasites on human T cells in vitro. A total of nine Leishmanin Skin Test+ volunteers with a history of self-healing CL (HCL) and seven healthy volunteers were included in this study. 5,6-carboxyfluroescein diacetate succinimidyl ester-labelled CD4+/CD8+ lymphocytes were cultured with killed Leishmania Lysate (Killed LL) or live Leishmania major (Live LM) and analysed for proliferation using flow cytometry. Culture supernatants were used for cytokine titration. In HCL volunteers, upon stimulation with killed LL, the number of proliferated CD4+/CD8+ cells was significantly more than that of unstimulated (P < 0·001) or live LM stimulated (P < 0·05) cells, or cells from controls (CD4+/CD8+: P < 0·05/P < 0·001). Stimulation of CD4+ cells with Live LM (P < 0·001) or Killed LL (P < 0·05) induced a significantly higher IFN-, production compared with that of controls, but Live LM induced significantly (P < 0·05) more IFN-, than Killed LL. A significantly (P < 0·05) higher IFN-, production was observed when CD8+ cells were stimulated with Live LM. Cells from HCL volunteers showed significantly more IL-10 production to Live LM stimulation compared with that of controls (CD4+: P < 0·05 /CD8+: P < 0·001) or cells stimulated with Killed LL (CD4+/CD8+: P < 0·001/P < 0·0005). Whereas Killed LL induced more proliferation response in purified T cells, Live LM induced cytokine production without significant induction of proliferation. The results from healed CL volunteers in this study could be implicated in further studies on T-cell response in vaccinated individuals. [source] A new standard for the assessment of disease progression in murine cutaneous leishmaniasisPARASITE IMMUNOLOGY, Issue 5 2000Lynden J.roberts Infection of mice with Leishmania major has been used both as a model for the cutaneous disease in humans and as a model for the more general control and function of helper T cells in immunity. In both cases, disease patterns and disease progression have been assessed by two complementary methods, lesion size and parasite burden in the draining lymph nodes. We propose a much improved method for the graphical representation of lesion development which conveys more information with better accuracy. We also describe a polymerase chain reaction method for determining parasite burden, which is faster and allows the analysis of larger numbers of experimental animals than the current limiting dilution analysis. Moreover, these methods are equally applicable to other infectious diseases, an obvious one being schistosomiasis. [source] Production, purification, crystallization and preliminary X-ray diffraction studies of the nucleoside diphosphate kinase b from Leishmania majorACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 11 2009Celisa Caldana Costa Tonoli Nucleoside diphosphate kinases (NDKs; EC 2.7.4.6) play an essential role in the synthesis of nucleotides from intermediates in the salvage pathway in all parasitic trypanosomatids and their structural studies will be instrumental in shedding light on the biochemical machinery involved in the parasite life cycle and host,parasite interactions. In this work, NDKb from Leishmania major was overexpressed in Escherichia coli, purified to homogeneity and crystallized using the sitting-drop vapour-diffusion method. The NDK crystal diffracted to 2.2,Å resolution and belonged to the trigonal crystal system, with unit-cell parameters a = 114.2, c = 93.9,Å. Translation-function calculations yielded an unambiguous solution in the enantiomorphic space group P3221. [source] Structure of Lmaj006129AAA, a hypothetical protein from Leishmania majorACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 3 2006Tracy Arakaki The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD) using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (Rfree = 0.229) at 1.60,Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif. [source] Crystallization and preliminary X-ray analysis of Leishmania major glyoxalase IACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 8 2005Antonio Ariza Glyoxalase I (GLO1) is a putative drug target for trypanosomatids, which are pathogenic protozoa that include the causative agents of leishmaniasis. Significant sequence and functional differences between Leishmania major and human GLO1 suggest that it may make a suitable template for rational inhibitor design. L. major GLO1 was crystallized in two forms: the first is extremely disordered and does not diffract, while the second, an orthorhombic form, produces diffraction to 2.0,Å. Molecular-replacement calculations indicate that there are three GLO1 dimers in the asymmetric unit, which take up a helical arrangement with their molecular dyads arranged approximately perpendicular to the c axis. Further analysis of these data are under way. [source] Efficacy of short-duration (twice weekly) intralesional sodium stibogluconate in treatment of cutaneous leishmaniasis in IndiaBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2010R.A. Bumb Summary Background, Cutaneous leishmaniasis (CL) is caused by Leishmania major and L. tropica in the old world. Bikaner, the ,Thar Desert', situated in the north-western corner of India, is an endemic pocket for CL caused by L. tropica. Skin lesions of CL heal slowly, causing disfiguring scars if remaining untreated. Current recommended treatment for CL comprises systemic administration of sodium stibogluconate (SSG) for 2,3 weeks. Five to seven injections of SSG intralesionally have also been found to be effective. Objectives, To determine the efficacy of a short-duration, twice-weekly intralesional SSG treatment for CL. Methods, Two hundred and twenty patients with CL having 298 lesions were included in the present study. They were divided into groups A and B (110 patients each). Patients were treated with five to seven intralesional injections of SSG in doses of 50 mg cm,2 of lesion either once (group A) or twice (group B) weekly. Improvement was recorded at 6, 8, 10, 12, 16, 20 and 24 weeks and the rate of complete cure was compared. Results, Complete cure rate at 6, 8 and 10 weeks was higher (20%, 57% and 73%, respectively) in group B as compared with group A (12%, 36% and 62%, respectively). The differences in cure rates at these time points were statistically significant (P < 0·05). The complete cure rate at 24 weeks was similar in both groups (96% in group B and 92% in group A). The remaining 4% and 8% of patients in groups B and A were ,nonresponders', respectively. No major side-effects were observed in either group. In all cured cases, there were no relapses reported up to 2 years after treatment. Conclusions, A short-duration, twice-weekly intralesional SSG treatment for CL accelerates cure and is highly effective and well tolerated. [source] Determination of intracellular efficacies of azithromycin against Leishmania major infection in human neutrophils in vitroCELL BIOCHEMISTRY AND FUNCTION, Issue 1 2003Mehmet Tanyuksel Abstract Azithromycin is one of a new class of antibiotics known as azalides. Azithromycin has high tissue affinity and this feature is thought to be due to the presence of two basic tertiary amine groups. Leishmania major, one of the causative agents of cutaneous leishmaniosis, is an obligate intracellular parasite. In this in vitro study, the potential anti-leishmanial effect of azithromycin upon intracellular forms namely the amastigote of L. major in mice peritoneal macrophages was investigated. L. major promastigotes were propagated in RPMI-1640 supplemented with 20% fetal calf serum in the log phase. The percentage of phagocytosis and microbiacidal activity of azithromycin on macrophages was assessed in the control and study groups by fluorescence microscopy, using acridine orange. Our results showed that at all the concentrations used (0.05, 0.1, 0.3, 0.6,,g,ml,1) azithromycin had no inhibitory effect on the phagocytic capacity of mouse peritoneal macrophages. Although no significant difference was observed for leishmaniacidal activity between the study and the control groups at a concentration of 0.05,,g,ml,1 (p>0.05), a significant (p<0.05) increase in leishmaniacidal activity was detected at 0.1, 0.3 and 0.6,,g,ml,1. As a result, azithromycin does not provide any contribution to the phagocytosis of L. major promastigotes in macrophages in vitro, but it increases the intracellular killing rates of amastigotes. These results suggest that it has a potential anti-leishmanial effect, and may provide a significant advantage in the treatment of the disease. Copyright © 2002 John Wiley & Sons, Ltd. [source] RNA interference in protozoan parasitesCELLULAR MICROBIOLOGY, Issue 6 2004Elisabetta Ullu Summary RNA interference or RNAi is defined as the mechanism through which gene-specific, double-stranded RNA (dsRNA) triggers degradation of homologous transcripts. Besides providing an invaluable tool to downregulate gene expression in a variety of organisms, it is now evident that RNAi extends its tentacles into both the nucleus and the cytoplasm and is involved in a variety of gene silencing phenomena. Here we review the current status of RNAi in protozoan parasites that cause diseases of considerable medical and veterinary importance throughout Africa, Asia and the Americas. RNAi was first discovered in Trypanosoma brucei, a species of the family Trypanosomatidae, and it rapidly became the method of choice to downregulate gene expression in these organisms. At the same time, mechanistic studies exposed a role for RNAi in the control of retroposon transcript abundance. Whereas RNAi is also present in T. congolense, other members of the same family of organisms, namely T. cruzi and Leishmania major, are RNAi-negative. In apicomplexan parasites, there is experimental evidence for RNAi in Plasmodium, but this is not supported by their genetic make up. In contrast, the genome of Toxoplasma gondii harbours gene candidates with convincing similarity to ,classical' RNAi genes. Thus, as previously shown in fungi, protozoan parasites are genetically heterogeneous as far as the RNAi pathway is concerned. Finally, database mining predicts that Entamoeba histolytica and Giardia intestinalis have an RNAi pathway and the presence of RNAi genes in Giardia supports the view that gene silencing by dsRNA appeared very early during evolution of the eukaryotic lineage. [source] Antileishmanial Physalins from Physalis minimaCHEMISTRY & BIODIVERSITY, Issue 9 2005Iqbal Choudhary Three new physalins (1,3) and a new withanolide 7 have been isolated from the whole plant of Physalis minima, along with three known physalins: physalin H (4), isophysalin B (5), and 5,,6, -epoxyphysalin B (6). Their structures were deduced on the basis of in-depth spectroscopic analyses. Compounds 1,6 showed significant in vitro leishmanicidal activities (0.92,19.4,,g/ml) against promastigotes of Leishmania major. [source] | ||||||||||||||||