L Carrera

National Institute of Allergy and Infectious Diseases, Maryland, United States

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Publications (9)31.04 Total impact

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    ABSTRACT: Few experimental studies on Leishmania tropica have been undertaken despite the importance of this parasite as the cause of cutaneous leishmaniasis, and now visceral disease, in the Old World. In part, this is due to the absence of convenient animals models, especially mice, for L. tropica infections. An anti-lipophosphoglycan (LPG) monoclonal antibody XCIV 1H2-A8 (T11), specific for L. tropica, was found to distinguish between culture-derived procyclic and metacyclic promastigotes. The antibody was used to negatively select for nonagglutinated metacyclic forms in stationary cultures, and the exceptional virulence of the purified metacyclics was verified by their infectivity for mouse macrophages in vitro and by their ability to produce cutaneous lesions in footpads of BALB/c mice. The lesions produced by three cutaneous isolates of L. tropica were nonulcerative and nonprogressive. Nonetheless, the lesions failed to heal, and high numbers of parasites could be recovered from footpads and draining lymph nodes up to 9 months after infection. Infections using L. tropica metacyclics purified from cutaneous, visceral and viscerotropic (Desert Storm) isolates of L. tropica were compared in both mouse and hamster models. Differences in disease progression were found that may reflect the parasite tissue tropism and virulence displayed by these strains in their human hosts. These findings suggest a role for parasite-related determinants in the clinical spectrum of disease.
    Experimental Parasitology 08/1998; 89(3):331-42. · 2.15 Impact Factor
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    ABSTRACT: Five-month-old beagle dogs were experimentally infected with amastigotes of Leishmania infantum and kept for 14 months. Infection course was monitored by clinical examination, serum protein variations, and levels of specific antibodies against Leishmania estimated by indirect immunofluorescence test and Western blotting (WB). Infected animals developed notable changes in serum protein levels reaching maximum protein concentrations 2-3 months postinfection (p.i.) related to the gamma-globulin fraction. Specific antibody titers were in good agreement with the serum protein rise, reaching immunofluorescence values of over 1:800 3 months p.i. Serial Western blotting analysis with L. infantum promastigotes protein showed a strong response against immunodominant antigens of 50-57, 42, and 29 kDa during most of the studied period with immunofluorescence titers of over 1:100 and in addition the response was remarkably homogeneous among the infected dogs. Immunoreactivity patterns displayed time-related variations; the response against 29 and 50-57 kDa was seen very early, followed by the reaction around 42, 76, and 86 kDa. In addition the recognition of peptides around 34-35.4 and 26 kDa was restricted to the acute phase of the experimental infection. Preliminary results obtained in naturally infected dogs seem to support the predictive value of the WB.
    Experimental Parasitology 04/1996; 82(2):139-46. · 2.15 Impact Factor
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    ABSTRACT: Leishmania major promastigotes were found to avoid activation of mouse bone marrow-derived macrophages (BMM0) in vitro for production of cytokines that are typically induced during infection with other intracellular pathogens. Coexposure of BMM0 to the parasite and other microbial stimuli resulted in complete inhibition of interleukin (IL) 12 (p40) mRNA induction and IL-12 release. In contrast, mRNA and protein levels for IL-1(alpha), IL-1(beta), tumor necrosis factor (TNF) alpha, and inducible NO synthase (iNOS) were only partially reduced, and signals for IL-10 and monocyte chemoattractant protein (MCP-1/JE) were enhanced. The parasite could provide a detectable trigger for TNF-alpha and iNOS in BMM0 primed with interferon (IFN) gamma, but still failed to induce IL-12. Thus IL-12 induction is selectively impaired after infection, whereas activation pathways for other monokine responses remain relatively intact. Selective and complete inhibition of IL-12(p40) induction was observed using BMM0 from either genetically susceptible or resistant mouse strains, as well as IL-10 knockout mice, and was obtained using promastigotes from cutaneous, visceral, and lipophosphoglycan-deficient strains of Leishmania. The impaired production of the major physiological inducer of IFN-gamma is suggested to underlie the relatively prolonged interval of parasite intracellular survival and replication that is typically associate with leishmanial infections, including those producing self-limiting disease.
    Journal of Experimental Medicine 03/1996; 183(2):515-26. · 13.21 Impact Factor
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    ABSTRACT: A preliminary trial on the extent of cross-antigenicity among the sheep strongylids Haemonchus contortus, Trichostrongylus colubriformis, Teladorsagia circumcincta and Nematodirus battus in 2.5- to 4-month-old lambs has been carried out using ELISA and Western blotting (WB). Cross antigenicity was tested using soluble extracts from adult and third stage larvae (L3) of H. contortus as antigenic source probed with sera from lambs with monospecific heterologous infections. There was cross-antigenicity between L3 of H. contortus and Trichostrongylus colubriformis in ELISA and WB. Immunodetection results with adult H. contortus antigen showed a closer relationship to Teladorsagia circumcincta. Certain heterologous sera reacted with H. contortus antigens more strongly than the homologous one, but sera from the H. contortus-infected animals had reactivity around the 25 kDa region from adult antigens which could have potential diagnostic use.
    Veterinary Parasitology 07/1994; 53(3-4):243-51. · 2.38 Impact Factor
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    ABSTRACT: Two isolates (skin and lymph node) of Leishmania infantum obtained from a naturally infected dog were cloned and the free pools of polyamines for both complete isolates and clones were determined. Putrescine (Put) and spermidine (Spd) levels were highly variable among the lines studied, ranging from 0.89 to 2.1 nmol Spd/10(7) promastigotes. The Put/Spd ratio was also variable (1.54-0.51) and correlated with the cell growth of the lines studied. There were important differences in the clones' sensitivities to difluoromethylornithine (DFMO) and Berenil, with some of the clones being almost refractory to the inhibitory effect of 50 microM DFMO, whereas the growth of others was reduced by 60%; similar findings were obtained with 50 microM Berenil. L. infantum sensitivities to DFMO and Berenil were correlated and apparently related to the values for the Put/Spd index.
    Parasitology Research 02/1994; 80(3):203-7. · 2.85 Impact Factor
  • Memórias do Instituto Oswaldo Cruz 01/1994; 89(4):649-50. · 1.36 Impact Factor
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    ABSTRACT: Sixteen- to eighteen-week-old lambs were infected with 2500 3rd stage larvae (L-3) of Haemonchus contortus or kept as uninfected controls. Two months later all animals were challenged with 5000 L-3 of this parasite. Soluble antigens of H. contortus L-3 and adult worms were analyzed by SDS-PAGE and Western blotting during experimental infection and challenge. Antigens from both sources, particularly of low molecular weight under reducing conditions, were recognised by the pooled sera of infected lambs. No single L-3 antigen was recognised by all infected lambs, whereas two peptides having around 25 and 26 kDa from adults were recognised by infected animals during the patency and could be of potential use in the diagnosis of lamb haemonchosis.
    Veterinary Parasitology 10/1993; 49(2-4):255-64. · 2.38 Impact Factor
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    ABSTRACT: Seven-week-old female kids of the Murciana-Granadina breed naturally infected with coccidia were superinfected with a multispecific Eimeria inoculum (300,000 oocysts) or treated to control the coccidial infection with Amprolium (50 mg kg-1 liveweight day-1; 4 days every 14 days); 80 days later both animal groups received 2500 third-stage larvae of a sheep-derived mixture of Trichostrongylus colubriformis (50%), Teladorsagia circumcincta (40%) and Haemonchus contortus (10%). Kids experimentally superinfected with Eimeria showed reduced food intake at the early patency period, higher numbers of oocysts passed at weaning time and lower liveweight gain than the Amprolium-medicated kids. In the Eimeria superinfected kids the trichostrongyle infection caused a tendency to result in chronic coccidial infections. Further, these animals had higher numbers of nematode eggs in their faeces, lower dressed weights on slaughter and inferior meat quality.
    Veterinary Parasitology 02/1993; 45(3-4):177-83. · 2.38 Impact Factor
  • Journal of Eukaryotic Microbiology 41(5):9S. · 2.16 Impact Factor