Physical map of the D6S149-D6S193 region on chromosome 6Q27 and its involvement in benign surface epithelial ovarian tumours

A detailed long range restriction map of the region defined by markers D6S149 and D6S193 on chromosome 6q27 has been constructed. This was achieved by YAC cloning and contig assembling of the same region. Seven YAC clones were found to span the almost 1000 Kb region flanked by the two markers which on the genetic map resulted to be 1.9 cM apart. With some of the characterized YAC clones we undertook a molecular cytogenetic analysis of 20 benign ovarian tumors. The rationale for this was the recent mapping to a region of chromosome 6q27, flanked by markers D6281 and D6S133, of a locus for the SV40-mediated immortalization of human cells (SEN6 gene). Noteworthy we found that the the D6S149-D6S193 region (comprised in the larger D6S281-D6S133 physical interval) was altered in all samples analysed adding support to the occurrence of a immortalization step in this type of tumors.     

Peripheral benzodiazepine receptor expression on leukocytes and neutrophil function during anticonvulsant monotherapy

AIM: To gain a full understanding of the concept of equity and means of promoting and monitoring a more equitable healthservice. BACKGROUND: With previous policy decisions having sidelined equity, a new government is likely to wish to reverse this trend. ORIGINS OF INFORMATION: Government and expert opinion. DATA ANALYSIS: A critical approach to previous literature. KEY ISSUES: Equity is not a unitary concept and so it is explored and dissected using the framework of: Distribution of Resources, Access and Uptake of Healthcare, Standards and Outcomes of Healthcare, Health Status. Means of improving and monitoring equity in these four areas are suggested. CONCLUSIONS: There are a number of ways of considering the concept of equity and for any fruitful discussion to occur there needs to be an agreed working definition. Specific topics are discussed where equity is lacking and a plan of action is suggested which is likely to improve equity in the areas identified.     

Resistivity Survey of the Subsurface Conditions in the Estuary of the Rio de la Plata

An electrical resistivity survey was performed at the estuary of the Rio de la Plata, as part of more comprehensive geotechnical investigations of the subsurface conditions. The studies were required for the emplacement of a 3.5-m-diameter conduit proposed for the discharge of the treated wastewater of the city of Buenos Aires. The soil profile at the site consists mainly of clays and silts underlain by a layer of dense sand. The dense sand layer is a confined aquifer, and the project required that the depth to the sand layer be perfectly determined. Previous geophysical surveys at the site and the general geotechnical conditions showed the inadequacy of seismic methods, which are usually adopted in similar environments. The resistivity method was determined to be a reliable alternative, even though there has been little experience in surveying shallow depth water for geotechnical investigations. The four-electrode Schlumberger electrode array was adopted for the resistivity survey. Some of the test devices were developed especially for the purpose of this project. Calibration of the method was achieved with data obtained from boreholes. The results show that the resistivity technique performed satisfactorily to the 40?m depth required in this project. As a result of the survey, the next geotechnical investigation was focused on a more reduced area and the required number of boreholes was reduced substantially.     

Functional evidence of atypical beta 3-adrenoceptors in the human colon using the beta 3-selective adrenoceptor antagonist, SR 59230A

The role of beta 3-adrenoceptors in human colonic circular smooth muscle was assessed in vitro by use of the beta 3-selective antagonist SR 59230A. Isoprenaline, in the presence of the selective beta-adrenoceptor antagonists CGP 20712A (beta 1) and ICI 118551 (beta 2), both at 0.1 microM, concentration-dependently relaxed the preparation (pEC50 = 5.22). This effect was potently and competitively antagonized by SR 59230A with a pA2 of 8.31, while its R,R enantiomer SR 59483A gave an apparent pKB of 6.21. Relaxation was likewise produced by CGP 12177A (pEC50 = 6.05), but not by BRL 37344. Although only one of these beta 3-selective agonists was effective, the remarkably high potency of SR 59230A as a stereospecific antagonist of non-beta 1 non-beta 2 relaxation of human colonic muscle by isoprenaline provides strong functional evidence of beta 3-adrenoceptors in that tissue.     

Pebbles and PebbleJuggler: software for accurate, unbiased, and fast measurement and analysis of nanoparticle morphology from transmission electron microscopy (TEM) micrographs

Pebbles is a user-friendly software program which implements an accurate, unbiased, and fast method to measure the morphology of a population of nanoparticles (NPs) from TEM micrographs. The morphological parameters of the projected NP shape are obtained by fitting intensity models to the TEM micrograph. Pebbles can be used either in automatic mode, where both fitting and validation are reliably carried out with minimal human intervention, and in manual mode, where the user has full control on the fitting and validation steps. Accuracy in diameter measurement has been shown to be ?1%. When operated in automatic mode, Pebbles can be very fast. The effective speed of 1 NP s(-1) has been achieved in favorable cases (packed monolayer of NPs). Since Pebbles is based on a local modeling procedure, it successfully treats cases such as low contrast NPs, NPs with significant diffraction scattering, and inhomogeneous background which often make conventional thresholding procedures fail. Pebbles is accompanied by PebbleJuggler, a software program for the statistical analysis of the sets of best-fit NP models created by Pebbles. Effort has been devoted to make Pebbles and PebbleJuggler the most user-friendly and the least user-tedious we could. Pebbles and PebbleJuggler are available at .     

Cost-benefit analysis of a mammography screening program extended to all the national territory

A cost-effectiveness analysis has been conducted in order to evaluate effects and costs of a nationwide mammographic breast cancer screening programme compared with no screening in a 30 years period. The analysis includes seven different phases of breast cancer, from the screening programme itself to the treatment of terminal illness. The estimates use italian published data and field studies. The calculations were performed with the Miscan computer simulation package: a programme providing for the screening of women aged 50-69 at two years intervals might be expected to result in a 1,650 deaths prevented and 14,500 years of life gained each year. The overall net costs of the programme were assessed at between 2,893 and 3,212 thousand million lire, the cost per life saved between 59.8 and 66.4 million lire and the cost per life-year gained between 6.6 and 7.3 million lire (between 10.7 and 11.5 million lire with a 5% discount rate, an estimate lower than that of German programme). The analysis produces important information for the Italian policy debate over mammography and it also contributes to the development of economic evaluation in our country.     

Factors affecting homologous overexpression of the Saccharomyces cerevisiae lanosterol 14 alpha-demethylase gene.

The Saccharomyces cerevisiae Lanosterol 14 alpha-demethylase (14DM) gene was overexpressed in S. cerevisiae using promoter sequences of the highly expressed S. cerevisiae glyceraldehyde-3-phosphate dehydrogenase (TDH3) gene. To investigate factors affecting 14DM overproduction, the levels of 14DM-specific RNAs, apoprotein, and heme protein, respectively, were determined and the 14DM-specific RNA levels compared with the RNA levels originating from the endogenous TDH gene(s). The quantitative measurements revealed that the 14DM steady-state RNA levels reached were some three- to five-fold below the theoretically expected values. With a view towards further improving expression of the 14DM gene, the spacing between the TDH3 promoter and the AUG was adjusted precisely and to rule out possible toxic effects exerted by the 14DM protein, the TDH3 promoter was placed under galactose regulation by introducing an UASG segment. Furthermore, the effects of the gene copy number on 14DM overproduction were investigated. From the analysis of the improved expression constructs five conclusions could be reached: (1) expression from the native 14DM gene is comparable to the expression driven by the TDH3 promoter-14DM fusion construct on single copy plasmid vectors; (2) expression from the TDH3 promoter-14DM construct on single-copy vectors is nearly as efficient as expression from the corresponding endogenous TDH3 gene; (3) the gene copy number has an effect on the relative expression levels of the TDH3 promoter-14DM constructs; (4) the steady-state amounts of protein produced are very nearly proportional to gene dosage; and (5) protein toxicity does not have a major impact on 14DM production. The maximum yield of 14DM was in the order of 7% of the total yeast protein and the maximum production of functional 14DM heme protein appears to be limited by the availability of heme.     

Interaction of spontaneous and organised screening for cervical cancer in Turin, Italy

In a screening programme for cervical cancer, coverage of the target population is a major determinant of effectiveness and cost-effectiveness and is one of the parameters for programme monitoring recommended by the "European Guidelines for Quality Assurance". An organised screening programme was started in Turin, Italy, in 1992. Spontaneous screening was already largely present, but coverage (proportion of women who had at least a test within 3 years) was low (< 50%) and distribution of smears uneven. No comprehensive registration of spontaneous smears was available. All women were invited for the first round, independently of their previous test history. Coverage was estimated by integrating routine data from the organised programme with data on spontaneous screening obtained by interviews of a random sample of 268 non-compliers to invitation and 167 compliers. Overall (spontaneous + organised) coverage was estimated to be 74% (95% CI, 71-78%). The proportion of the target population covered as an effect of invitation was estimated to be 17% (95% CI, 15-20%). Invitations were successful in increasing coverage in previously poorly screened groups. Although 20-25% of compliers was estimated to have had further tests before the end of the round, we estimated that switching to a 3-year interval saved approximately 0.26 tests per complier. This suggests that invitations to an organised programme even to previously covered women, can be a cost-effective policy. Our method of estimating overall coverage can be useful in many other European areas where a comprehensive registration of smears is not available.