Expression of oestrogen receptor beta (ERβ1) protein in human breast cancer biopsies

Oestrogen action is mediated via specific receptors that act as ligand-activated transcription factors. A monoclonal antibody specific to the C-terminus of human oestrogen receptor beta has been characterized and the prevalence of expression of oestrogen receptor beta protein investigated in a well defined set of breast cancers. Reverse transcription-polymerase chain reaction analysis of RNA from tissue biopsies detected oestrogen receptor beta in all samples examined. The anti-oestrogen receptor beta antibody cross reacted specifically with both long (∼59 Kd) and short (∼53 Kd) forms of recombinant oestrogen receptor beta. Western blot analysis of breast tumours contained both forms of oestrogen receptor beta protein although in some samples lower molecular weight species (32–45 Kd) were identified. Fifty-one breast cancer biopsies were examined using immunohistochemistry; 41 (80%) were immunopositive for oestrogen receptor alpha, 48 (94%) were immunopositive for oestrogen receptor beta and 38 (74.5%) co-expressed both receptors. Expression of oestrogen receptor beta was exclusively nuclear and occurred in multiple cell types. There was no quantitative relationship between staining for the two ERs although in tumours in which both receptors were present immunoexpression of oestrogen receptor alpha was invariably more intense. The significance of oestrogen receptor beta protein expression in breast cancers to therapy remains to be determined but the availability of a well characterized antibody capable of detecting oestrogen receptor beta in archive material will facilitate the process

Medication knowledge, certainty, and risk of errors in health care: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Medication errors are often involved in reported adverse events. Drug therapy, prescribed by physicians, is mostly carried out by nurses, who are expected to master all aspects of medication. Research has revealed the need for improved knowledge in drug dose calculation, and medication knowledge as a whole is poorly investigated. The purpose of this survey was to study registered nurses' medication knowledge, certainty and estimated risk of errors, and to explore factors associated with good results.</p> <p>Methods</p> <p>Nurses from hospitals and primary health care establishments were invited to carry out a multiple-choice test in pharmacology, drug management and drug dose calculations (score range 0-14). Self-estimated certainty in each answer was recorded, graded from 0 = very uncertain to 3 = very certain. Background characteristics and sense of coping were recorded. Risk of error was estimated by combining knowledge and certainty scores. The results are presented as mean (±SD).</p> <p>Results</p> <p>Two-hundred and three registered nurses participated (including 16 males), aged 42.0 (9.3) years with a working experience of 12.4 (9.2) years. Knowledge scores in pharmacology, drug management and drug dose calculations were 10.3 (1.6), 7.5 (1.6), and 11.2 (2.0), respectively, and certainty scores were 1.8 (0.4), 1.9 (0.5), and 2.0 (0.6), respectively. Fifteen percent of the total answers showed a high risk of error, with 25% in drug management. Independent factors associated with high medication knowledge were working in hospitals (p < 0.001), postgraduate specialization (p = 0.01) and completion of courses in drug management (p < 0.01).</p> <p>Conclusions</p> <p>Medication knowledge was found to be unsatisfactory among practicing nurses, with a significant risk for medication errors. The study revealed a need to improve the nurses' basic knowledge, especially when referring to drug management.</p

Feed-Forward Microprocessing and Splicing Activities at a MicroRNA–Containing Intron

The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6–exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5′ splice site (5′SS), but not in the 3′SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5′SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs