Abstract:
:Glucocorticoid (GC) effects are mediated by the glucocorticoid receptor (GR). Several studies have demonstrated that a lower number of receptors per cell were associated with poor GC response. The regulation of GR expression is complex; the levels of GR can be autologously regulated by its ligand and also by transcriptional, post-transcriptional and post-translational mechanisms. Using three human myeloma cell lines that parallel the development of GC resistance, this work describes the mechanism involved in the downregulation of GR expression. The decreased expression was neither due to mutations in the gene encoding GR, NR3C1, nor due to methylation of the promoters. A gradual decrease in NR3C1 transcripts was seen during the development of resistance, the level of expression of exon 1 to 2 RNA fragments remained the same in sensitive and resistant cell lines but a chromatin immunoprecipitation assay demonstrated that RNA polymerase II, detectable throughout exon 2 to 3 in the sensitive cells, was undetectable on exon 3 in the resistant variant, suggesting lower or no transcription at this site. These studies demonstrated that downregulation of NR3C1 mRNA in a resistant cell line involves a block to transcriptional elongation within intron B of NR3C1. This block may represent an important element in the regulation of GR expression.
journal_name
Br J Haematoljournal_title
British journal of haematologyauthors
Sánchez-Vega B,Gandhi Vdoi
10.1111/j.1365-2141.2008.07549.xsubject
Has Abstractpub_date
2009-03-01 00:00:00pages
856-64issue
6eissn
0007-1048issn
1365-2141pii
BJH7549journal_volume
144pub_type
杂志文章abstract::We aimed to identify and classify cases of paediatric myelodysplastic syndromes (MDS) occurring in Britain to estimate the incidence of this rare group of diseases, investigate the results of therapy and identify prognostic risk factors. Patients aged below 15 years at diagnosis were collected from England, Scotland a...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.2003.04361.x
更新日期:2003-06-01 00:00:00
abstract::Aplastic anaemia (AA) is considered as an immune-mediated bone marrow failure syndrome. The mechanism is involved with a variety of immune molecules including interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α) and interleukins (ILs). IL-27 is a novel member of the IL-12 family, which mediates T cell response and e...
journal_title:British journal of haematology
pub_type: 杂志文章
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abstract::To explore the potential efficacy of l-asparaginase treatment in acute myeloid leukaemia (AML) patients, we studied the in vitro resistance of French-American-British (FAB) subtypes of childhood AML to l-asparaginase using a methyl-thiazol-tetrazolium assay. We tested leukaemic cells obtained from 177 common acute lym...
journal_title:British journal of haematology
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doi:10.1046/j.1365-2141.2003.04703.x
更新日期:2003-12-01 00:00:00
abstract::The specific sodium pump antagonist ouabain was used to study the effect of sodium pump inhibition on granulopoietic colony formation by normal human bone marrow cells cultured in soft agar for 7 d. Suppression of colony formation was dose-dependent and occurred at a low and reproducible concentration. The use of an e...
journal_title:British journal of haematology
pub_type: 杂志文章
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abstract::Thirty-four patients with refractory multiple myeloma were treated with 4-d continuous infusions of vincristine and adriamycin in combination with 4-d pulsed high-dose dexamethasone (VAD). Of 31 evaluable patients, 16 entered a complete remission (50%) and three a partial remission (10%). No difference in response rat...
journal_title:British journal of haematology
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abstract::Heparin binding on polymorphonuclear leucocytes (PMNL) was characterized. Heparin binding was specific, rapid, saturable and reversible. One single class of heparin binding sites was found with a dissociation constant of 1.22 mumol/l and 7.7 x 10(6) sites per PMNL. The binding was independent of the anticoagulant acti...
journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
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更新日期:2005-09-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
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更新日期:1975-01-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
pub_type: 杂志文章
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abstract::Iron chelators are increasingly combined clinically but the optimal conditions for cellular iron mobilization and mechanisms of interaction are unclear. Speciation plots for iron(III) binding of paired combinations of the licensed iron chelators desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) suggest co...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/bjh.13512
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abstract::Canine cyclic haematopoiesis (CH) appears to be a multipotential stem cell defect, possibly due to an intrinsic marrow defect. The in vitro adherent marrow cells of the cyclic haematopoietic (CH) dog were cultured as underlayers beneath normal dog nonadherent marrow cells. The marrow granulocyte-committed colony formi...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1982.tb01961.x
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abstract::The prevalence of obesity has increased substantially over recent years. Clinicians are increasingly being challenged with making uncertain anticoagulant dosing decisions, as the optimal dosing strategy for most anticoagulants in the obese patient population remains unknown. Research published to date suggests that th...
journal_title:British journal of haematology
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journal_title:British journal of haematology
pub_type: 杂志文章,meta分析
doi:10.1046/j.1365-2141.1997.4453255.x
更新日期:1997-12-01 00:00:00
abstract::Of 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0.5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive educ...
journal_title:British journal of haematology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2004-08-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章,多中心研究
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
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doi:10.1046/j.1365-2141.2001.02637.x
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journal_title:British journal of haematology
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journal_title:British journal of haematology
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doi:10.1046/j.1365-2141.1996.00725.x
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journal_title:British journal of haematology
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journal_title:British journal of haematology
pub_type: 杂志文章,评审
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journal_title:British journal of haematology
pub_type: 杂志文章
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更新日期:2002-01-01 00:00:00
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journal_title:British journal of haematology
pub_type: 杂志文章
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journal_title:British journal of haematology
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更新日期:2000-03-01 00:00:00
abstract::The polymerase chain reaction (PCR) assay was used to detect human parvovirus B19 DNA in 38 blood products and start plasma pools from five different manufacturers. The products examined were albumin, factor VIII, intravenous (i.v.) and intramuscular (i.m) immunoglobulin batches. The majority of pools from all the man...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1046/j.1365-2141.1996.d01-1679.x
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abstract::We report a series of 20 patients with the myelodysplastic syndrome (MDS) each with a coexistent lymphoid or plasmacytic neoplasm. In none of the patients did chemotherapy play a part in the pathogenesis. The possible reasons for the coincidence of these conditions are discussed. The frequency and variety of associate...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.1986.tb07505.x
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abstract::Steady-state haemoglobin (Hb) desaturation is a common finding in sickle cell anaemia (Hb SS) that could predispose to stroke by limiting oxygen delivery to the brain. To determine its association with the risk of overt stroke, we examined the relationship between daytime Hb saturation measured by pulse oximetry (SpO(...
journal_title:British journal of haematology
pub_type: 杂志文章
doi:10.1111/j.1365-2141.2009.07652.x
更新日期:2009-05-01 00:00:00