RESUMO
The PML protein localizes to regions of the nucleus known as nuclear bodies or PODs. However, in t(15;17) Acute Promyelocytic Leukemia (APL) blasts, PML is found in a micro-punctate pattern. In order to test the hypothesis that delocalization of PML from PODs is necessary for APL, we investigated the interaction of the t(5;17) APL fusion protein NPM-RAR with PML. NPM-RAR localizes diffusely throughout the nucleoplasm. NPM-RAR does not alter the localization of PML in transfected HeLa cells, and does not associate with PML in vitro. These studies suggest that NPM-RAR does not interact with PML.
Assuntos
Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 5/genética , Leucemia Promielocítica Aguda/genética , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Proteínas Supressoras de Tumor/genética , Animais , Células COS , Chlorocebus aethiops , Células HeLa , Humanos , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/imunologia , Proteínas Nucleares/metabolismo , Proteínas de Fusão Oncogênica/imunologia , Reação em Cadeia da Polimerase/métodos , Proteína da Leucemia Promielocítica , Ligação Proteica , Sensibilidade e Especificidade , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/imunologia , Proteínas Supressoras de Tumor/metabolismoRESUMO
Haemophilia A and B are X-linked disorders resulting from deficiency of Factor VIII and IX, respectively. Clinical sequellae of Factor VIII or IX deficiency include spontaneous and traumatic haemorrhages into joints, soft tissues, and muscles. The cornerstone of therapy has been replacement of the deficient factor, historically with pooled-plasma derivatives. The unfortunate blood-borne infection transmission (such as HIV, hepatitis B and C viruses), inhibitor formation, immunosuppression, and, in certain cases, thrombosis by these products has spawned major advances and innovations in the manufacture of clotting products. Recombinant technology has virtually eliminated transmissible disease risk; yet, the presence of albumin in second and third generation recombinant products raises, at the least, theoretical risk of prions and parvovirus B19. Other non-infectious complications, including inhibitor formation, allergic reactions, and thrombosis, remain formidable concerns. Despite this, recombinant factors remain the most attractive treatment approach for haemophilia. Future improvement awaits the development of safe and effective gene transfer technology.
Assuntos
Fator IX , Fator VIII , Fator VII , Hemofilia A , Hemofilia B , Proteínas Recombinantes , Fator IX/efeitos adversos , Fator IX/economia , Fator IX/uso terapêutico , Fator VII/efeitos adversos , Fator VII/economia , Fator VII/uso terapêutico , Fator VIII/efeitos adversos , Fator VIII/economia , Fator VIII/uso terapêutico , Fator VIIa , Feminino , Hemofilia A/tratamento farmacológico , Hemofilia A/genética , Hemofilia A/fisiopatologia , Hemofilia B/tratamento farmacológico , Hemofilia B/genética , Hemofilia B/fisiopatologia , Humanos , Masculino , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/economia , Proteínas Recombinantes/uso terapêuticoRESUMO
Despite improved survival after liver transplantation (OLTX) in HIV-positive individuals treated with highly active antiretroviral therapy (HAART), some transplant candidates do not survive to OLTX. To determine if pretransplant outcome is related to severity of liver disease and/or HIV infection, we prospectively evaluated 58 consecutive HIV-positive candidates seen at a single center from 1997-2002. Of the 58, 15 (25.9%) were transplanted, whereas 21 (36.2%) died before OLTX, a median one month of evaluation, with more than half of those (12 of 21, 57.1%) dying from infection. By contrast, of 1,359 HIV-negative candidates, 860 (63.3%) were transplanted, whereas 211 (15.5%) died before OLTX (P < 0.001). The cumulative survival following initial evaluation was significantly shorter among HIV-positive than HIV-negative candidates (880 vs. 1,427 days, P = 0.035, Breslow) but was not related to the initial pretransplant MELD score (16 vs. 15), INR (1.5 vs. 1.5), creatinine (1.3 vs. 1.3 mg/dL), or total bilirubin (6.6 vs. 5.7 mg/dL), respectively, all P > 0.05. Among untransplanted HIV-positive candidates, the 21 who died did not differ from the 22 surviving in initial MELD (15 vs. 13), CD4 (230 vs. 327/microL), HIV load (both < 400 copies/mL), HAART intolerance (10/21, 47.6% vs. 10/22, 45.4%), or HCV infection (16/21, 76.2% vs. 16/22, 72.3%), all P > 0.05. Further, the 21 did not differ from the 15 transplanted in pre-OLTX CD4, HIV load, or MELD score, all P > 0.05. In conclusion, pretransplant survival appears shorter in HIV-positive OLTX candidates and is unrelated to severity of liver or HIV disease. Further study is warranted to determine risk factors for poorer pretransplant outcomes.