RESUMO
Metacyclic trypomastigotes of Trypanosoma cruzi express a developmentally regulated 82 kDa surface glycoprotein (gp82) that has been implicated in the mammalian cell invasion. When the non-infective epimastigote stage of the parasite was transfected with a vector containing the gp82 gene, an 82 kDa surface glycoprotein, which was indistinguishable from the metacyclic stage protein, was expressed. In contrast, when the same gene was expressed in transfected mammalian cells, although a large amount of protein was produced, it was not imported into the endoplasmic reticulum and glycosylated. This blockage in targeting and processing could be partially compensated for by the addition of a virus haemagglutinin signal peptide to the amino terminus of gp82. Thus, the requirements for membrane protein processing are distinct in mammals and T. cruzi, and an intrinsic feature of the gp82 prevents subsequent sorting to the mammalian cell surface. These results could be useful in the development of new DNA vaccines against T. cruzi employing parasite genes encoding immunodominant surface glycoproteins.
Assuntos
Glicoproteínas de Membrana/genética , Processamento de Proteína Pós-Traducional , Sinais Direcionadores de Proteínas , Trypanosoma cruzi/genética , Sequência de Aminoácidos , Animais , Chlorocebus aethiops , Clonagem Molecular , Cães , Glicosilação , Mamíferos , Glicoproteínas de Membrana/metabolismo , Dados de Sequência Molecular , Transfecção , Células VeroRESUMO
As part of a survey of human leishmaniasis in Nicaragua we examined phenotypic and genotypic characteristics of 40 Leishmania isolates. We identified 3 distinct parasites associated with cutaneous disease in this area; Leishmania panamensis (40% of cases), Leishmania braziliensis (33%), and a strain which exhibits the heterozygous isoenzyme and DNA fingerprinting patterns expected of a L. panamensis/L. braziliensis hybrid (27%). There was complete correlation between the isoenzyme and DNA data for each of the putative hybrids examined. All of the 'hybrids' were obtained from foci in the northern region of the country where L. panamensis and L. braziliensis occur sympatrically. These observations provide strong evidence for sexual reproduction in New World Leishmania populations and suggest that it is of taxonomic and epidemiological significance.
Assuntos
Leishmania braziliensis/patogenicidade , Leishmania/patogenicidade , Leishmaniose Cutânea/etiologia , Animais , Impressões Digitais de DNA , DNA de Protozoário/genética , Feminino , Genes de Protozoários , Genética Populacional , Genótipo , Humanos , Hibridização Genética , Isoenzimas/genética , Leishmania/genética , Leishmania/isolamento & purificação , Leishmania braziliensis/genética , Leishmania braziliensis/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Masculino , NADH NADPH Oxirredutases/genética , Nicarágua , Fenótipo , Reprodução/genéticaRESUMO
STUDY OBJECTIVE: To determine whether acyclovir administered orally affects the duration and severity of varicella in otherwise normal children. DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Patients' residence and university hospital clinic. PATIENTS: One hundred five children between 5 and 16 years of age with laboratory-confirmed varicella entered the study. Of the 102 who were included in the final analysis, 50 received acyclovir and 52 received placebo. INTERVENTION: Placebo or acyclovir was given orally four times daily, for 5 to 7 days. The acyclovir dose was adjusted as follows: 5 to 7 years of age, 20 mg/kg; 7 to 12 years, 15 mg/kg; and 12 to 16 years, 10 mg/kg. MEASUREMENTS AND MAIN RESULTS: Acyclovir recipients, compared with the placebo group, defervesced sooner (median, 1 day vs 2 days; p = 0.001), experienced onset of cutaneous healing sooner, as reflected by a decrease in number of lesions (median, 3 days vs 2 days; p = 0.002), and had fewer skin lesions (median, 500 vs 336; p = 0.02). Acyclovir did not significantly change the rate of complications of varicella (10% in the acyclovir group vs 13.5% among placebo subjects). Adverse drug effects were not observed. Acyclovir recipients had lower geometric mean serum antibody titers to varicella-zoster virus than their placebo counterparts 4 weeks after the onset of illness, but antibody titers in both groups were similar 1 year later. CONCLUSIONS: These results provide evidence that acyclovir is useful and well tolerated for treatment of varicella in otherwise healthy children.