RESUMO
We recently proposed a representation of the bivariate survivor function as a mapping of the hazard function for truncated failure time variates. The representation led to a class of estimators that includes van der Laan's repaired nonparametric maximum likelihood estimator (NPMLE) as an important special case. We proposed a Greenwood-like variance estimator for the repaired NPMLE but found somewhat poor agreement between the empirical variance estimates and these analytic estimates for the sample sizes and bandwidths considered in our simulation study. The simulation results also confirmed those of others in showing slightly inferior performance for the repaired NPMLE compared to other competing estimators as well as a sensitivity to bandwidth choice in moderate sized samples. Despite its attractive asymptotic properties, the repaired NPMLE has drawbacks that hinder its practical application. This paper presents a modification of the repaired NPMLE that improves its performance in moderate sized samples and renders it less sensitive to the choice of bandwidth. Along with this modified estimator, more extensive simulation studies of the repaired NPMLE and Greenwood-like variance estimates are presented. The methods are then applied to a real data example.
Assuntos
Funções Verossimilhança , Análise de Sobrevida , Estatísticas não Paramétricas , Estados UnidosRESUMO
The interface between luminal contents and intestinal epithelium constitutes the largest area of interaction between the host and the environment. There is now strong evidence that the gene product of the multidrug resistant pump (MDR) plays a critical role in host-bacterial interactions in the gastrointestinal tract and maintenance of intestinal homeostasis. This review highlights the efflux mechanism in the intestinal epithelium which is mediated by the multidrug resistant pump, also known as P-glycoprotein 170. Current studies promise to provide further insights into the contribution of the MDR1 gene in the pathogenesis of inflammatory and malignant disorders of the gastrointestinal tract.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Resistência a Múltiplos Medicamentos/genética , Gastroenteropatias/genética , Genes MDR/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Corticosteroides/farmacologia , Animais , Transformação Celular Neoplásica/genética , Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Doença de Crohn/genética , Sistema Enzimático do Citocromo P-450/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Humanos , Família Multigênica , Polimorfismo de Nucleotídeo Único/genética , RatosRESUMO
Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with clinically proven vasculitis have been described as reacting with proteins present in the granules of human neutrophils. We have studied sera from 59 ANCA positive patients to further characterize the antibody response. In addition to the antigens previously identified in the vasculitic syndromes (myeloperoxidase and serine proteinase 3) the majority of these sera contained antibodies that reacted with a cytosolic extract of neutrophils on Western blots. Nearly 40% of these sera had antibodies directed against a cytosolic protein(s) of molecular mass 48 kD. This protein was purified from neutrophil cytosol by ammonium sulphate fractionation, anion exchange and reverse phase chromatography. Amino acid sequence analysis of a proteolytic fragment of this protein identified it as alpha enolase. The anti-enolase antibodies only recognized the alpha isoform and were present in sera giving either a pANCA or cANCA staining pattern by indirect immunofluorescence. Antibodies to alpha enolase were also found in sera from patients with systemic lupus erythematosus, particularly those with renal disease. We conclude that the antibody response in ANCA positive vasculitis is not restricted to neutrophil granule proteins.
Assuntos
Autoanticorpos/sangue , Autoantígenos/sangue , Fosfopiruvato Hidratase/imunologia , Vasculite/imunologia , Sequência de Aminoácidos , Anticorpos Anticitoplasma de Neutrófilos , Autoantígenos/genética , Autoantígenos/isolamento & purificação , Citosol/enzimologia , Citosol/imunologia , Humanos , Nefrite Lúpica/enzimologia , Nefrite Lúpica/imunologia , Dados de Sequência Molecular , Neutrófilos/enzimologia , Neutrófilos/imunologia , Fosfopiruvato Hidratase/sangue , Vasculite/enzimologiaRESUMO
ADPase has been purified from bovine spleen. Electrophoresis revealed a minor contaminent in the preparation that may represent ADPase that has been decreased in size by limited proteolysis during extraction and purification. The native enzyme behaves on SDS/PAGE as a 100-kDa protein but ADPase is a glycoprotein and so its electrophoretic behaviour may be anomalous. The apparent molecular mass is decreased to 70 kDa after removal of carbohydrate by treatment with a glycosidase. The use of a cross-linking reagent followed by electrophoresis suggests that the enzyme is composed of a single subunit. The specific activity of the purified material was 115 U/mg protein. The enzyme catalyses the hydrolysis of nucleoside di- and tri-phosphates but nucleoside monophosphates are not acted upon. The Km for ADP (approx. 10-15 microM) is unaffected by the state of purification of the enzyme, but catalytic activity of the purified material is stimulated by inclusion of detergent in the assay system and by calcium ions. Maximum activity is seen at pH 8.0-8.5 with ADP as substrate but the optimum shifts to 7.5-8.0 for ATP hydrolysis.
