RESUMO
A retroviral element (MSRV) defining a family of genetically inherited endogenous retroviruses (HERV-W) has recently been characterized in cell cultures from patients with multiple sclerosis (MS). To address the possible relationship with MS, direct detection of circulating virion RNA was proposed but revealed technically difficult to perform in standardized conditions, in the face of multiple endogenous HERV-W copies. A parallel approach has evaluated MSRV potential pathogenicity in relation to characteristic features of multiple sclerosis, in particular, T-lymphocyte-mediated immunopathology. We report here that MSRV particles induce T-lymphocyte response with a bias in the Vbeta16 chain usage in surface receptor, whatever the HLA DR of the donor. A recombinant MSRV envelope-but not core-protein reproduced similar nonconventional activation. Molecular analysis of Vbeta CDR3 showed that Vbeta16 expansions are polyclonal. Our results thus provide evidence that MSRV envelope protein can trigger an abnormal immune response with similar characteristics to that of superantigens.
Assuntos
Retrovirus Endógenos/imunologia , Ativação Linfocitária/imunologia , Esclerose Múltipla/virologia , Infecções por Retroviridae/imunologia , Linfócitos T/imunologia , Proteínas do Envelope Viral/imunologia , Antígenos Virais/imunologia , Células Cultivadas , Citocinas/metabolismo , Retrovirus Endógenos/genética , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Esclerose Múltipla/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Proteínas Recombinantes/imunologia , Infecções por Retroviridae/virologia , Linfócitos T/metabolismo , Células Tumorais Cultivadas , Vírion/imunologiaRESUMO
Reinfection pattern among 6- to 20-year-old subjects was studied over 24 months in two Mauritanian villages of intense Schistosoma haematobium infection after a targeted chemotherapy with praziquantel involving the whole community. Subjects received treatment according to the presence of haematuria/proteinuria and this indirect screening technique was able to identify 98-100% of the heavily infected subjects (50 + eggs/10 ml). The two villages differed with respect to their characteristics, quality of follow-up and reinfection pattern. The post-treatment 6-month cumulative incidence during the two transmission periods following the chemotherapy, estimated from a subset of 116 subjects, was 18.0% and 20.5%. Reinfection rates were higher among males (Cox-Mantel: P = 0.0015), among children 6-10 years of age than older (P = 0.0078) and among subjects with more than 50 eggs/10 ml of urine before treatment than subjects with a lower egg output (P = 0.009). A Cox proportional hazard regression model was fitted and confirmed that gender, age and pretreatment level of infection were predictors of the rate of reinfection but that there was no interaction between these predictors.
Assuntos
Esquistossomose Urinária/epidemiologia , Adolescente , Adulto , Fatores Etários , Animais , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Tábuas de Vida , Masculino , Mauritânia/epidemiologia , Contagem de Ovos de Parasitas , Praziquantel/uso terapêutico , Prevalência , Recidiva , Análise de Regressão , Fatores de Risco , Esquistossomose Urinária/tratamento farmacológico , Esquistossomose Urinária/urina , Fatores SexuaisRESUMO
Two hundred thirty-one patients with a first acute myocardial infarction were randomly allocated within 5 h after the onset of symptoms either to treatment with anisoylated plasminogen streptokinase activator complex (APSAC), 30 U over 5 min, or to conventional heparin therapy, 5,000 IU in a bolus injection. Heparin was reintroduced in both groups 4 h after initial therapy at a dosage of 500 IU/kg per day. One hundred twelve patients received APSAC and 119 received heparin within a mean period of 188 +/- 62 min after the onset of symptoms. Both groups were similar in age, location of the acute myocardial infarction, Killip functional class and time of randomization. Elective coronary arteriography was performed on an average of 4 +/- 1.2 days after initial therapy. Follow-up radionuclide angiography and thallium-201 single photon emission computed tomography were performed before hospital discharge. Infarct size was estimated from single photon emission computed tomography and expressed as a percent of total myocardial volume. The patency rate of the infarct-related artery was 77% in the APSAC group and 36% in the heparin group (p less than 0.001). Left ventricular ejection fraction determined from contrast angiography was significantly higher in the APSAC group than in the heparin group. This was true for the entire study group (0.53 +/- 0.13 versus 0.47 +/- 0.12; p = 0.002) as well as for the subgroups of patients with anterior and inferior wall infarction (0.47 +/- 0.13 versus 0.40 +/- 0.11; p = 0.04 and 0.56 +/- 0.10 versus 0.51 +/- 0.11; p = 0.02, respectively). At 3 weeks, the difference remained significant for the anterior myocardial infarction subgroup. A significant 31% reduction in infarct size was found in the APSAC group (33% for the anterior infarction subgroup [p less than 0.05] and 16% for the inferior infarction subgroup [p = NS]). A close inverse relation was found between the values of left ventricular ejection fraction and infarct size (r = -0.73, p less than 0.01). By the end of a 3 week follow-up period, seven APSAC-treated patients and six heparin-treated patients had died. In conclusion, the early infusion of APSAC in acute myocardial infarction produced a high early patency rate, significant limitation of infarct size and significant preservation of left ventricular systolic function, mainly in anterior wall infarction.