RESUMO
Disruption of gene silencing by Polycomb protein complexes leads to homeotic transformations and altered developmental-phase identity in plants. Here we define short genomic fragments, known as Polycomb response elements (PREs), that direct Polycomb repressive complex 2 (PRC2) placement at developmental genes regulated by silencing in Arabidopsis thaliana. We identify transcription factor families that bind to these PREs, colocalize with PRC2 on chromatin, physically interact with and recruit PRC2, and are required for PRC2-mediated gene silencing in vivo. Two of the cis sequence motifs enriched in the PREs are cognate binding sites for the identified transcription factors and are necessary and sufficient for PRE activity. Thus PRC2 recruitment in Arabidopsis relies in large part on binding of trans-acting factors to cis-localized DNA sequence motifs.
Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/genética , Repressão Epigenética/genética , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Complexo Repressor Polycomb 2/fisiologia , Proteínas do Grupo Polycomb/fisiologia , Elementos de Resposta/genética , Motivos de Aminoácidos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/biossíntese , Proteínas de Arabidopsis/genética , Sítios de Ligação , DNA de Plantas/genética , DNA de Plantas/metabolismo , Flores/crescimento & desenvolvimento , Ontologia Genética , Ensaios de Triagem em Larga Escala , Família Multigênica , Folhas de Planta/ultraestrutura , Plantas Geneticamente Modificadas , Ligação Proteica , Mapeamento de Interação de Proteínas , Fatores de Transcrição/metabolismoRESUMO
Persistent infection with the hepatitis B virus (HBV) [as indicated by chronic HBV surface antigenemia (HBsAg)] continues to be an important problem in end-stage renal disease (ESRD) patients and specifically in those receiving maintenance hemodialysis (HD). Patients on HD who are HBsAg-positive for a year have little chance of ever eliminating the virus; hence, clearance of HBsAg is a rare event in long-term HD patients. We report the case of a 62-year-old diabetic woman who was HBsAg-positive at the time she started HD and remained so until 10 years later when she became HBsAg-negative followed by the development of hepatitis B surface antibody (anti-HBs). Prior to her seroconversion, she suffered a persistent infection of her HD arteriovenous graft (AVG) that required prolonged antibiotics and several surgical procedures. We speculate that this immune stimulation contributed to her seroconversion.
Assuntos
Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Diálise Renal , Insuficiência Renal Crônica/terapia , Antibacterianos/uso terapêutico , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Bacteriemia/tratamento farmacológico , Feminino , Hepatite B/imunologia , Humanos , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/etiologiaRESUMO
Monitoring the quality of dialysis care has long been a component of the Medicare ESRD program. As part of the 2008 Medicare Improvements for Patients and Providers Act (MIPPA), Congress mandated the Quality Incentive Program (QIP), which linked measures of care quality to payments. The legislation embraced the idea that this linkage of federal money to performance would encourage the purchase of greater 'value.' The first 2 program years for the QIP use a simple scoring methodology and a limited scope of quality metrics. For payment year 2014 (performance period calendar year 2012), the program changes substantially, with an expanded number of quality measures and a more complex scoring methodology. In this article, we describe the program structure, quality measures, scoring system, and financial impact.
Assuntos
Centers for Medicare and Medicaid Services, U.S./economia , Atenção à Saúde/economia , Falência Renal Crônica/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde/economia , Melhoria de Qualidade/economia , Indicadores de Qualidade em Assistência à Saúde/economia , Reembolso de Incentivo , Diálise Renal/economia , Benchmarking/economia , Centers for Medicare and Medicaid Services, U.S./legislação & jurisprudência , Centers for Medicare and Medicaid Services, U.S./normas , Atenção à Saúde/legislação & jurisprudência , Atenção à Saúde/normas , Financiamento Governamental , Regulamentação Governamental , Custos de Cuidados de Saúde , Política de Saúde/economia , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/economia , Avaliação de Processos e Resultados em Cuidados de Saúde/legislação & jurisprudência , Avaliação de Processos e Resultados em Cuidados de Saúde/normas , Guias de Prática Clínica como Assunto , Desenvolvimento de Programas , Melhoria de Qualidade/legislação & jurisprudência , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/legislação & jurisprudência , Indicadores de Qualidade em Assistência à Saúde/normas , Reembolso de Incentivo/legislação & jurisprudência , Reembolso de Incentivo/normas , Diálise Renal/normas , Resultado do Tratamento , Estados UnidosRESUMO
Drug-induced acute renal failure is a commonly encountered mode of renal injury in the hospitalized patient. Vancomycin is a frequently used antibiotic in patients with Gram-positive bacterial infections. In the present study, we evaluated an index case of a patient who developed severe acute granulomatous interstitial nephritis and provided a review of the reported cases of vancomycin-induced acute renal failure in the literature. A Medline search revealed a total of 11 cases of vancomycin-induced interstitial nephritis. In 2 reported cases, interstitial nephritis has been reported with associated granuloma formation. However, the role of T cells in the formation of interstitial nephritis and in the choice of therapeutic modalities in this scenario has not been evaluated in the past. In the index case, we have evaluated the effect of treatment on the basis of the type of cellular infiltrates and provided a follow-up by carrying out the repeat biopsy.
Assuntos
Antibacterianos/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/terapia , Vancomicina/efeitos adversos , Doença Aguda , Adulto , Biópsia , Humanos , Rim/patologia , Masculino , Nefrite Intersticial/patologiaRESUMO
Most forms of renal disease associated with monoclonal gammopathy result from deposition of monoclonal immunoglobulins or their subunits in different compartments of the kidney. Renal monoclonal immunoglobulin deposition disease (MIDD) is defined by linear deposits of monoclonal light-chain components in renal basement membranes, often producing a nodular sclerosing glomerulopathy. Clinical features of renal MIDD include proteinuria, with or without renal failure, and an association with dysproteinemias. Three types of renal MIDD have been reported, namely, light-chain deposition disease (LCDD), light- and heavy-chain deposition disease (LHCDD), and heavy-chain deposition disease (HCDD). Reports on LHCDD are rare. At present, follow-up data are limited on the management of renal monoclonal protein deposition disease. We present a case of monoclonal protein deposition in the kidney containing both heavy and light chains with unique characteristics that did not conform to any of the above previous established classes. Its follow-up revealed an unusual relapsing and remitting course in response to treatment.
Assuntos
Síndrome Nefrótica , Paraproteinemias , Feminino , Glomerulonefrite Membranoproliferativa/imunologia , Humanos , Cadeias Pesadas de Imunoglobulinas/imunologia , Cadeias Leves de Imunoglobulina/imunologia , Pessoa de Meia-Idade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/imunologia , Síndrome Nefrótica/patologia , Síndrome Nefrótica/terapia , Paraproteinemias/diagnóstico , Paraproteinemias/imunologia , Paraproteinemias/patologia , Paraproteinemias/terapia , Insuficiência RenalRESUMO
Chromatin remodeling is emerging as a central mechanism for patterning and differentiation in multicellular eukaryotes. SWI/SNF chromatin remodeling ATPases are conserved in the animal and plant kingdom and regulate transcriptional programs in response to endogenous and exogenous cues. In contrast with their metazoan orthologs, null mutants in two Arabidopsis thaliana SWI/SNF ATPases, BRAHMA (BRM) and SPLAYED (SYD), are viable, facilitating investigation of their role in the organism. Previous analyses revealed that syd and brm null mutants exhibit both similar and distinct developmental defects, yet the functional relationship between the two closely related ATPases is not understood. Another central question is whether these proteins act as general or specific transcriptional regulators. Using global expression studies, double mutant analysis, and protein interaction assays, we find overlapping functions for the two SWI/SNF ATPases. This partial diversification may have allowed expansion of the SWI/SNF ATPase regulatory repertoire, while preserving essential ancestral functions. Moreover, only a small fraction of all genes depends on SYD or BRM for expression, indicating that these SWI/SNF ATPases exhibit remarkable regulatory specificity. Our studies provide a conceptual framework for understanding the role of SWI/SNF chromatin remodeling in regulation of Arabidopsis development.
Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Arabidopsis/genética , Montagem e Desmontagem da Cromatina , Regulação da Expressão Gênica de Plantas , Proteínas Nucleares/metabolismo , Adenosina Trifosfatases/genética , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Perfilação da Expressão Gênica , Genes Reporter , Dados de Sequência Molecular , Mutação , Proteínas Nucleares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transcrição GênicaRESUMO
Pim-2 is a transcriptionally regulated oncogenic kinase that promotes cell survival in response to a wide variety of proliferative signals. Deregulation of Pim-2 expression has been documented in several human malignancies, including leukemia, lymphoma, and multiple myeloma. Here, we show that the ability of Pim-2 to promote survival of cells is dependent on nuclear factor (NF)-kappaB activation. Pim-2 activates NF-kappaB-dependent gene expression by inducing phosphorylation of the oncogenic serine/threonine kinase Cot, leading to both augmentation of IkappaB kinase activity and a shift in nuclear NF-kappaB from predominantly p50 homodimers to p50/p65 heterodimers. Blockade of NF-kappaB function eliminates Pim-2-mediated survival in both cell lines and primary cells, and both Cot phosphorylation and expression are required for the prosurvival effects of Pim-2. Although Pim-2 cooperates with Myc to promote growth factor-independent cell proliferation, this feature is abrogated by NF-kappaB blockade. The ability of Pim-2 to serve as an oncogene in vivo depends on sustained NF-kappaB activity. Thus, the transcriptional induction of Pim-2 initiates a novel NF-kappaB activation pathway that regulates cell survival.
Assuntos
Ativação Linfocitária/fisiologia , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Animais , Sequência de Bases , Primers do DNA , Ensaio de Desvio de Mobilidade Eletroforética , Humanos , Hidrólise , Proteínas I-kappa B/metabolismo , Células Jurkat , Camundongos , Camundongos Transgênicos , FosforilaçãoRESUMO
The collapsing variant of focal segmental glomerulosclerosis is a fulminant lesion characterized by rapid progression to end-stage renal disease. Substantial in vivo and in vitro evidence suggests that lipids, particularly low density lipoprotein (LDL), can contribute to the progression of glomerulosclerosis as they do in atherosclerosis. The nephrotic syndrome is typically associated with marked elevation of LDL and suppression of high density lipoprotein (HDL), abnormalities which may, accelerate both of these lesions. We report the case of a patient who presented with heavy proteinuria and hypertension and was found to have collapsing focal segmental glomerulosclerosis as well as, surprisingly, a markedly elevated HDL level. Despite the poor prognosis of this lesion, over a 3-year period the patient maintained normal renal function and has experienced a decline in her proteinuria to below-nephrotic levels while maintaining an elevated HDL level. Though this is only a single report, it may nevertheless be worthwhile to consider the possibility that HDL levels could potentially modulate the course of glomerular disease.