Expression of luminal and basal cytokeratins in human breast carcinoma

We have examined basal and luminal cell cytokeratin expression in 1944 cases of invasive breast carcinoma, using tissue microarray (TMA) technology, to determine the frequency of expression of each cytokeratin subtype, their relationships and prognostic relevance, if any. Expression was determined by immunocytochemistry staining using antibodies to the luminal cytokeratins (CKs) 7/8, 18 and 19 and the basal markers CK 5/6 and CK 14. Additionally, assessment of alpha-smooth muscle actin (SMA) and oestrogen receptor status (ER) was performed. The vast majority of the cases showed positivity for CK 7/8, 18 and 19 indicating a differentiated glandular phenotype, a finding associated with good prognosis, ER positivity and older patient age. In contrast, basal marker expression was significantly related to poor prognosis, ER negativity and younger patient age. Multivariate analysis showed that CK 5/6 was an independent indicator for relapse free interval. We were able to subgroup the cases into four distinct phenotype categories (pure luminal, mixed luminal/basal, pure basal and null), which had significant differences in relation to the biological features and the clinical course of the disease. Tumours classified as expressing a basal phenotype (the combined luminal plus basal and the pure basal) were in a poor prognostic subgroup, typically ER negative in most cases. These findings provide further evidence that breast cancer has distinct differentiation subclasses that have both biological and clinical relevance.     

Primary care funding, contract status, and outcomes: an observational study

BACKGROUND: The introduction of the Quality and Outcomes Framework (QOF) provides a quantitative way of assessing quality of care in general practice. We explore the achievements of general practice in the first year of the QOF, with specific reference to practice funding and contract status. AIM: To determine the extent to which differences in funding and contract status affect quality in primary care. DESIGN OF STUDY: Cross-sectional observational study using practice data obtained under the Freedom of Information Act 2000. SETTING: One hundred and sixty-four practices from six primary care trusts (PCTs) in England. METHOD: Practice data for all 164 practices were collated for income and contract status. The outcome measure was QOF score for the year 2004-2005. All data were analysed statistically. RESULTS: Contract status has an impact on practice funding, with Employed Medical Services (EMS) and Personal Medical Services (PMS) practices receiving higher levels of funding than General Medical Services (GMS) practices (P<0.001). QOF scores also vary according to contract status. Higher funding levels in EMS practices are associated with lower QOF scores (P=0.04); while GMS practices exhibited the opposite trend, with higher-funded practices achieving better quality scores (P<0.001). CONCLUSION: GMS practices are the most efficient contract status, achieving high quality scores for an average of pound 62.51 per patient per year. By contrast, EMS practices are underperforming, achieving low quality scores for an average of pound 105.37 per patient per year. Funding and contract status are therefore important factors in determining achievement in the QOF.     

The human ovarian teratocarcinoma cell line PA-1 demonstrates a single translocation: analysis with fluorescence in situ hybridization, spectral karyotyping, and bacterial artificial chromosome microarray

Cell lines derived from tumors contain numerous chromosomal aberrations and are the focus of study in tumor evolution. The ovarian teratocarcinoma cell line PA-1 demonstrates a single chromosomal aberration: a reciprocal t(15;20)(p11.2;q11.2). A complete molecular genetic analysis was undertaken to characterize this cell line. The PA-1 cell line was studied with fluorescence in situ hybridization (FISH), spectral karyotyping (SKY), bacterial artificial chromosome (BAC) microarray, and Western blotting. Amplification of 20q is frequently implicated in both breast and ovarian cancer; this region contains a number of oncogenes including MDM2, ZNF217, and the ovarian tumor marker WFDC2 (alias HE4). FISH revealed gene amplification of AIB1 (now known as NCOA3) but not STK15 (now known as AURKA). Immunoblot analysis demonstrated 3.6-fold overexpression of the AIB1 protein product, but no elevation of the STK15. BAC cancer gene microarray analysis showed gene amplification of > or =1.20 for five oncogenes. The presence of a consistent single change in PA-1, the t(15;20)(p11.2;q11.2), suggests that the aberration is significant with respect to the transformation status of the cell line. This translocation appears to cause overexpression of AIB1 (and perhaps other proteins), which may provide an immortalizing effect on this cell line.     

Malignant Melanoma of Soft Parts Involving the Head and Neck Region: Review of Literature and Case Report

Malignant melanoma of soft parts (MMSP) was originally described as a distinct entity by Enzinger in 1965 and was termed “clear cell sarcoma of tendons and aponeuroses” because of its association with tenosynovial structures. It has been shown immunophenotypically and ultrastructurally that this tumor is derived from neuroectoderm and shares a number of features with cutaneous melanoma. Over 95% of MMSPs present in the extremities, with the head and neck region (1.9%) being an unusual site. This study presents an additional case of MMSP of the head and neck region involving the posterior cervical region in a 15-year-old Hispanic male and reviews the literature on MMSP. Ultrastructural examination showed rudimentary cell attachments, smooth cell membranes, discontinuous basal lamina, scanty glycogen, and occasional premelanosomes in some tumor cells. Cytogenetic analysis showed a reciprocal translocation between the long arms of chromosomes 12 and 22 [t(12:22)(q13;q12.2)], characteristic for MMSP and not seen in cutaneous melanoma. Survival in MMSP has been correlated with tumor size, tumor necrosis, and ploidy status. Overall reported clinical outcome for this tumor is as follows: died of disease, 45%; alive with disease, 23%; no evidence of disease, 30%; and died of other causes, 2%. MMSP represents a distinct entity with a characteristic ultrastructural appearance and a tumor defining cytogenetic translocation.     

Binding and antimineralocorticoid activities of spirolactones in toad bladder

The role of the soluble pool (cytoplasmic or cytosolic) of [3H]-aldosterone binding sites in the toad bladder was assessed by the use of two spirolactones, prorenone and spironolactone as a reference drug. Prorenone fulfills all the criteria for a specific competitive antagonist of aldosterone for its effect on Na+ transport. Compared with spironolactone (Ki approximately equal to 1 microM), prorenone was about eightfold less potent (Ki approximately equal to 8 microM). Competition for [3H]aldosterone binding sites by spironolactone and prorenone revealed an order of potency (spironolactone greater than prorenone) that corresponded to their antagonist activities in the Na+ transport assay. There was a linear correlation between the effects of the two spirolactones on the aldosterone-stimulated Na+ transport and their ability to displace [3H]aldosterone from its binding sites in the soluble pool. Finally [3H]prorenone binding sites were detected in the soluble pool but an insignificant number of antagonist-receptor complexes were found associated with the nuclear pool. Our study indicates that the aldosterone binding sites of the soluble pool are indeed mineralocorticoid receptors, which are probably the first intracellular mediators leading to an increased Na+ reabsorption.     

How clients with religious or spiritual beliefs experience psychological help‐seeking and therapy: A qualitative study

This qualitative study explored the process of help‐seeking and therapy among clients with religious or spiritual beliefs. Ten clients who were currently in, or had recently finished, therapy were interviewed. Participants reported using their religious or spiritual beliefs to cope with their psychological problems before and during therapy. Prior to therapy, they were worried that secular‐based help might weaken their faith. However, the experience of having psychological distress and the process of receiving therapy were both perceived as strengthening to faith and ultimately part of a spiritual journey. Contrary to expectations, a match between the spirituality or religious affiliation of the therapist and client was not considered important. This implies that the ‘religiosity gap’ between secular therapists and clients with religious/spiritual beliefs is bridgeable. Copyright © 2007 John Wiley & Sons, Ltd.     

A course on the transition to adult care of patients with childhood-onset chronic illnesses.

Children with special health care needs born today have a 90% chance of surviving into adulthood, making their transition to adult systems of care an issue that will affect almost all physicians. However, many adult generalists and specialists are not familiar with the management of chronic diseases that begin in childhood. While the public health system has made transition to appropriate adult care a priority, and many specialty organizations have endorsed this concept, there are no published studies addressing how the concept of transition can be taught to medical students or residents. The authors describe a one-week course for medical students, begun in 2001 at their institution, that addresses the transition for youth with special health care needs, emphasizing patient and family-centered care, cultural competence, and decision making in end-of-life issues. Cystic fibrosis, a common genetic disease with increasing life expectancy, is used as the model for the course. Involvement of interdisciplinary faculty, interviews with youth with special health care needs and family caregivers, readings from academic and nonacademic literature, and group discussions are presented as teaching methods. Key insights based on experience with the course are the need to include the voices of patients and families, the use of faculty from various professions and specialties to model interdisciplinary care, and the insight that problems specific to transition offer into contemporary health care financing. Future studies should measure the impact of such courses on students' knowledge of transition issues, and determine essential information required for physicians in practice.     

Three highly polymorphic microsatellites at the human myelin oligodendrocyte glycoprotein locus, 100 kb telomeric to HLA-F : Characterization and relation to HLA haplotypes

The MOG locus, located on chromosomal bands 6p21.3-p22 and mapped about 100 kb telomeric to HLA-F, was isolated from cosmid ICRFcl09A2434 and shown to contain three microsatellites. These CA-repeat polymorphic markers were characterized in a sample of 173 healthy unrelated individuals and 84 DNAs from the HLA Workshop reference panel, by a method combining fluorescence labeling of PCR products and use of an automated DNA sequencer. For the three markers, frequencies of heterozygotes are well predicted from allele frequencies by the Hardy—Weinberg rule, which suggests that problems of allele nonamplification are unlikely. Typing of cell lines homozygous in the HLA region allowed unambiguous definition of 81 HLA-MOG haplotypes and showed that several HLA ancestral haplotypes extended to the MOG region. The high degree of polymorphism (59%, 51%, and 81% at the three loci, respectively, and 87% at the haplotype level) makes these new markers informative for association or linkage studies with diseases such as hemochromatosis or multiple sclerosis, and for studies aimed at precisely delineating the site of crossover in chromosomes in which recombination occurred in the distal part of the HLA class I region.