RESUMO
Members of the Plasmodium falciparum var gene family encode clonally variant adhesins, which play an important role in the pathogenicity of tropical malaria. Here we employ a selective panning protocol to generate isogenic P.falciparum populations with defined adhesive phenotypes for CD36, ICAM-1 and CSA, expressing single and distinct var gene variants. This technique has established the framework for examining var gene expression, its regulation and switching. It was found that var gene switching occurs in situ. Ubiquitous transcription of all var gene variants appears to occur in early ring stages. However, var gene expression is tightly regulated in trophozoites and is exerted through a silencing mechanism. Transcriptional control is mutually exclusive in parasites that express defined adhesive phenotypes. In situ var gene switching is apparently mediated at the level of transcriptional initiation, as demonstrated by nuclear run-on analyses. Our results suggest that an epigenetic mechanism(s) is involved in var gene regulation.
Assuntos
Variação Antigênica/genética , Antígenos CD , Adesão Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Plasmodium falciparum/genética , Transcrição Gênica/genética , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Sequência de Aminoácidos , Animais , Antígenos de Diferenciação/metabolismo , Encéfalo , Células CHO , Linhagem Celular , Sulfatos de Condroitina/metabolismo , Cricetinae , Endotélio/citologia , Eritrócitos/parasitologia , Genes de Protozoários , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Glicoproteínas de Membrana , Dados de Sequência Molecular , NAD+ Nucleosidase/metabolismo , Plasmodium falciparum/citologia , Plasmodium falciparum/patogenicidade , RNA Mensageiro/análise , RNA de Protozoário/análise , SaimiriRESUMO
The aim of this study was to assess the prognostic value of total serum bilirubin (TSB), gamma-glutamyl transpeptidase (GGT) and the TSB/GGT ratio in 129 consecutive cirrhotic patients, and to determine how seven other clinical and biochemical variables affect the prognostic value of these measurements. The Cox model and log rank test were used to compare survival rates at 1 year. Considered alone, encephalopathy, ascites, TSB, prothrombin time, serum albumin, GGT and the TSB/GGT ratio (TSB expressed in mumoles per liter and GGT in IU per liter were associated to the 1-year survival (p less than 0.10). The estimated per cent surviving at the end of 1 year was 20% for those with encephalopathy and 59% for those without, 46% and 62% for those with and without ascites, 28% for those with TSB greater than 3.0 mg per dl, 68% for those with TSB less than or equal to 3.0 mg per dl, 44% for those with GGT less than or equal to 100 IU per liter, 60% for those with GGT greater than 100 IU per liter, and 12% for those with TSB/GGT greater than 1, 66% for those with TSB/GGT less than or equal to 1. With the Cox model, which was used to assess the combined effect of several prognostic variables, GGT was the only biochemical variable which added significant prognostic value to TSB. The combination of TSB and GGT added significant prognostic value to encephalopathy and ascites.
