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Notes: Objective To assess the frequency of abnormal values for hormone measurements commonly used in the biochemical diagnosis of polycystic ovary syndrome (PCOS).Design Hormone measurements in 63 unselecled women with clinical and ultrasound diagnosis of PCOS attending gynaecological and general endocrine clinics in a District General Hospital were compared with those from a group of 20 normal ovula-tory controls in the early follicular phase of their cycles.Measurements Serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH ratio, total testosterone, derived free testosterone, sex hormone binding globulin, androstenedione, and dehydroepiandrosterone (DHEA) were measured by radioimmunoassays. LH and FSH measured by two different assays.Results The mean serum LH and LH/FSH ratio were significantly (P〈0.01) higher in the women with PCOS compared with the normal group, but these two measurements were in the abnormal range for only 35% and 41–44%, respectively. Absolute gonadotrophin values were significantly different using the two assay methods, which employed the same reference preparation as standard. Mean serum total testosterone concentration was significantly higher in the PCOS group and was the most frequently (70%) abnormal biochemical marker for PCOS. Sex hormone binding globulin (SHBG) did not differ significantly between the two groups but showed a negative correlation with body mass index in women with PCOS. The combination of SHBG and testosterone to derive a free testosterone value did not further aid the biochemical diagnosis of PCOS. Androstenedione was significantly higher in the PCOS group than in the control group, with a frequency of 53%. There was no significant difference in DHEA-S between the two groups.Conclusion When typical ovarian ultrasound appearances plus the clinical features of oligomenorrhoea and/or hirsuitism were used to define PCOS total testosterone was the best single hormonal marker of the condition. Testosterone, androstenedione or LH, either alone or in combination, were raised in 86% of women with PCOS and these should be the definitive hormonal tests. Using LH/FSH ratio as a biochemical criterion for diagnosis of PCOS should be abandoned because of its low sensitivity. To be of value the normal range for all hormones should be precisely defined in a group of regularly ovulating women in the early follicular phase of the cycle for the assay used in each laboratory.

Notes: Crystal structure solution by anomalous dispersion methods has been greatly facilitated using the rapidly tunable station 9.5 at the Daresbury SRS. Both SIROAS and MAD techniques, with IP data, have been used in the phasing of a brominated nucleotide and a seleno deaminase, respectively. The electron density maps in each case are interpretable. Throughput of projects could be improved upon with a better duty cycle detector. Another category of data collection is that at very high resolution. Detailed structure refinement pushes the limits of resolution and data quality. Station 9.5 has been used to collect high resolution (1.4 A(ring)) native data for the protein concanavalin A. This utilized very short wavelengths (0.7 A(ring)), the image plate, and crystal freezing. A total of 155 407 measurements from two crystals benefited from the on-line nature of the IP detector device, but a slow and quick pass are required to capture the full dynamic range of the data. There are data seen to 1.2 A(ring) and beyond for a pure Mn substituted form of the protein, but a higher intensity still is required to actually record these data. By comparison, trials at CHESS, on a multipole wiggler (station A1) with a CCD (without image intensifier) system, yield native concanavalin A data to 0.98 A(ring) and beyond. This demonstrates that the combination of yet higher intensity and the ease of use of a CCD offers worthwhile improvements; in this case an increase in the data by a factor of (1.4/0.98)3, thus at least doubling the data to parameter ratio for protein structure model refinement and potentially opening up direct structure determination of proteins of the size of concanavalin A (25 kDa).Finally, possibilities at ESRF and further detector developments, such as mosaic CCDs and scintillator coatings, offer further impetus for the field. These include more intense rapidly tunable beams for anomalous dispersion-based structure solution and "ideal'' higher resolution data collection and reactivity studies. ESRF BL19 is described; facilities on BL19 will include a system for freezing and storing crystals at cryogenic temperatures, so that data can be recorded from the same crystal on different runs. Overall, there have been tremendous strides made in this field in the last 15 years, and yet further improvements are to come. © 1995 American Institute of Physics.

Notes: Many years ago the idea of collecting voluminous quantities of weak reflection intensities from a protein crystal, at high resolution, was a particular challenge [J.R. Helliwell (1979) Daresbury Study Weekend DL/SCI R13, pp. 1–6]. The combination of insertion devices with very high x-ray fluxes at short x-ray wavelengths, sensitive CCD detectors, and freezing of crystals have provided the means to certainly match those best hopes. So much so that the data can best be described as ultrahigh resolution, at least as evidenced in our studies of the 25000 molecular weight plant protein concanavalin A. (The intrinsic property of this protein is to bind sugar molecules; it is implicated in cell-to-cell recognition processes and is widely used as a laboratory diagnostic tool.) At CHESS we have used a 0.9 A(ring) wavelength beam on station A1, fed by a 24 pole multipole wiggler. Both an imaging plate system and the Princeton 1k CCD detector [M. Tate et al., J. Appl. Cryst. 28, 196 (1995)] have been used on this experimental setup to collect diffraction data sets from frozen concanavalin A crystals (saccharide-free crystal form). The rapid readout of the CCD was most convenient compared with the image plate and its associated scanning and erasing. Moreover the data processing results towards the edges of the detectors, 0.98 A(ring), show that the CCD is much better than the image plate at recording these weaker data (Rmerge(I) 13% versus 44%, respectively). The poor performance of the image plate with weak signals has of course been documented by the Daresbury detector group [R. Lewis, J. Synchrotron Radiation 1, 43 (1994)]. However, the aperture of the CCD used was limiting here. Very recently, in another run at CHESS with the CCD on A1, we have been able to record diffraction data to 0.94 A(ring) by further offsetting the detector. We again found that the reflections are still strong at the edge. Clearly the use of even shorter wavelengths than 0.9 A(ring) would be very useful in matching the solid angle of the diffraction pattern to the available detector aperture, for a reasonable crystal-to-detector distance. In addition, absorption errors in the data can be simultaneously removed by such a strategy. Indeed, finely focused x-ray beams of, say 0.5 A(ring) wavelength, are especially well suited to high energy, low emittance synchrotron radition (SR) machines. Some initial tests carried out on CHESS station F2 with a 0.5 A(ring) wavelength beam and the CCD detector show an improvement in the R-merge(I) to 2 A(ring) resolution, in comparison to the data collected at 0.9 A(ring) wavelength (i.e., 2.3% versus 3.0%). In conclusion, the diffraction resolution limit (0.94 A(ring)) seen already in our concanavalin A studies can be further enhanced and is important for the most detailed molecular model refinement (and the testing of structure solving strategies), in conjunction with novel spectroscopic and theoretical studies. This paper builds upon the work of Deacon et al. [Rev. Sci. Instrum. 66, 1287 (1995)]. © 1996 American Institute of Physics.

Notes: In a continuing drive to reduce the radiation exposure of nuclear workers, many routine aspects of nuclear plant maintenance and refurbishment are increasingly undertaken by robotic or remote handling tools. Accurate “as built” documentation of plant records is vital to the successful planning and execution of such operations since an unexpected obstruction or undocumented site modification may result in a costly disruption or even failure of the intervention. In recognition of the importance of such documentation, a recent European Community† sponsored project has been directed towards the development of techniques for cost effective survey and modelling of such plant. This paper will detail the rationale behind the design of such a system and will describe typical results from a number of pilot projects.

Notes: Peripheral nerve catheters are being used increasingly to manage acute pain. Whilst acknowledged as effective, their broader implications for patient outcome are less clear. In this case report, we describe the way in which not only was the pain management of an ischaemic leg successful via a sciatic nerve catheter, but decision-making around this strategy affected outcome.

Notes: The enzyme hydroxymethylbilane synthase (HMBS, E.C. 4.3.1.8) catalyzes the conversion of porphobilinogen into hydroxymethylbilane, a key intermediate for the biosynthesis of heme, chlorophylls, vitamin B12 and related macrocycles. The enzyme is found in all organisms, except viruses. The crystal structure of the selenomethionine-labelled enzyme ([SeMet]HMBS) from Escherichia coli has been solved by the multi-wavelength anomalous dispersion (MAD) experimental method using the Daresbury SRS station 9.5. In addition, [SeMet]HMBS has been studied by MAD at the Grenoble ESRF MAD beamline BM14 (BL19) and this work is described especially with respect to the use of the ESRF CCD detector. The structure at ambient temperature has been refined, the R factor being 16.8% at 2.4 Å resolution. The dipyrromethane cofactor of the enzyme is preserved in its reduced form in the crystal and its geometrical shape is in full agreement with the crystal structures of authentic dipyrromethanes. Proximal to the reactive C atom of the reduced cofactor, spherical density is seen consistent with there being a water molecule ideally placed to take part in the final step of the enzyme reaction cycle. Intriguingly, the loop with residues 47–58 is not ordered in the structure of this form of the enzyme, which carries no substrate. Direct experimental study of the active enzyme is now feasible using time-resolved Laue diffraction and freeze-trapping, building on the structural work described here as the foundation.