Abstract: We report the discovery of two well-defined tidal tails emerging from the sparse remote globular cluster Palomar 5. These tails stretch out symmetrically to both sides of the cluster in the direction of constant Galactic latitude and subtend an angle of 26 on the sky. The tails have been detected in commissioning data of the Sloan Digital Sky Survey, providing deep five-color photometry in a 25-wide band along the equator. The stars in the tails make up a substantial part (~) of the current total population of cluster stars in the magnitude interval 19.5 ≤ i* ≤ 22.0. This reveals that the cluster is subject to heavy mass loss. The orientation of the tails provides an important key for the determination of the cluster's Galactic orbit.

Abstract: Fortran 77 software implementing the SPG method is introduced. SPG is a nonmonotone projected gradient algorithm for solving large-scale convex-constrained optimization problems. It combines the classical projected gradient method with the spectral gradient choice of steplength and a nonmonotone line-search strategy. The user provides objective function and gradient values, and projections onto the feasible set. Some recent numerical tests are reported on very large location problems, indicating that SPG is substantially more efficient than existing general-purpose software on problems for which projections can be computed efficiently.

Abstract: M.R. BERESFORD, P.W. ANDREW AND G. SHAMA. 2001. Aims: To investigate the adhesion of Listeria monocytogenes 10403S to 17 different, food-use approved materials representing metals, rubbers and polymers. Methods and Results: Adhesion assays were conducted by placing ‘coupons’ of the materials in planktonic cultures at 30°C, and then immediately withdrawing them (‘short contact’) or leaving them submerged in the cultures for 2 h. Adherent cells were recovered by sonication. In the short contact experiments, the logarithm of the mean viable counts ranged from 3·67 ± 0·43 to 4·78 ± 0·38. After 2 h contact time, the numbers of adherent cells had increased significantly for all materials with the exception of polypropylene. The highest count (6·33 ± 0·31) recorded was for stainless steel 405. Conclusions: Adhesion to a wide range of materials was time-dependent and characterized by reversible and irreversible stages. Significance and Impact of the Study: Adhesion test protocols must account for cell carry-over and cells which are only weakly bound. Material selection may only have a limited role in reducing food contamination by listeria.

Abstract: Wistar dams were exposed to 500 ppm of Pb, as Pb acetate, or 660 ppm Na acetate in drinking water during pregnancy and lactation. Male pups at 23 (weaned) or 70 days (adult) of age were submitted to behavioral evaluation and Pb determination. The behaviors evaluated were: locomotor activity (open-field test), motor coordination (rotarod test), exploratory behavior (holeboard test), anxiety (elevated plus maze and social interaction tests), and learning and memory (shuttle box). Pb levels were measured in the blood and cerebral regions (hippocampus and striatum) of dams and pups. The results of the present report demonstrated that exposure to Pb during pregnancy and lactation induces in weaned pups hyperactivity, decreased exploratory behavior, and impairment of learning and memory. These alterations were observed at blood Pb levels in the range that may be attained in children chronically exposed to low levels of Pb (21+/-3 microg/dl). Regarding adults, the results demonstrated that the regimen of exposure adopted induces anxiety in these animals at nondetectable blood Pb levels.

Abstract: U-Pb dating of metamorphic and igneous rocks from the Hunza Valley and Baltoro regions of the Karakoram Mountains in northern Pakistan addresses the thermal and magmatic evolution of the thickened Asian plate crust before, during, and after the collision of the Kohistan arc and the Indian plate. Crustal thickening and high- temperature, sillimanite-grade metamorphism in the southern Karakoram Mountains followed the collision and accretion of the Kohistan arc during the Late Cretaceous. U-Pb ages of metamorphic monazites from sillimanite gneisses in the Hunza Valley are 63.3 ± 0.4 Ma, ca. 50–52 Ma, and 44.0 ± 2.0 Ma, and monazites from a kyanite-grade schist from the Baltoro region are 28.0 ± 0.5 Ma. Metamorphic monazites from a highly graphitic garnet + staurolite schist from the Hunza Valley yield a crystallization age of 16.0 ± 1.0 Ma. Sillimanite gneisses from the Dassu dome have magmatic zircons of 1855 ± 11 Ma, reflecting a Proterozoic continental crustal source, and metamorphic monazites of 5.4 ± 0.2 Ma. Magmatism was also sporadic; early granodiorite, monzogranite, and leucogranite dikes yield zircon, monazite, and uraninite ages of 50–52 Ma and 35.0 ± 1.0 Ma. Widespread lower crustal melting during the latest Oligocene–early Miocene culminated with emplacement of the Baltoro Plutonic Unit in the Karakoram batholith that cuts deformation fabrics in the high-grade gneisses to the south. The youngest magmatic phase dated is the 9.3 ± 0.2 Ma Sumayar leucogranite pluton. On the basis of detailed structural field studies combined with U-Pb geochronology, sillimanite-grade metamorphism was either a protracted event lasting as long as 20 m.y. (64–44 Ma) or peaked at different times within the lower crust following collision of first, the Kohistan arc, and later, the Indian plate. We also present evidence for southward propagation of peak metamorphism and postmetamorphic thrusting and folding of isograds within the past 5 m.y. Detailed geochronology shows that deformation, metamorphism, and magmatism in the middle and lower crust of the south Asian margin has been occurring within the Karakoram metamorphic complex for more than 60 m.y. Similar processes may also have affected the unplumbed depths of the south Tibetan crust.

Abstract: The different attributes of the Patient Evaluation Measure (PEM) questionnaire were investigated in 80 patients with a fracture of the scaphoid. Assessments were made at 2, 8, 12, 26 and 52 weeks. Reliability was assessed by measurement of the internal consistency of the different questions in 275 completed PEM forms. Cronbach's alpha, which needs to lie between 0.7 and 0.9, was 0.9 for the PEM. Pain, tenderness, swelling, wrist movement and grip strength correlated with the PEM score confirming the validity of the assessment. Changes in the different variables between visits correlated significantly with changes in the PEM score; its effect size and standardised response mean were comparable to those of grip strength and movement, confirming the responsiveness of this questionnaire. Gender, dominance and the side injured did not influence the scores. Older patients had a poorer outcome as assessed by the score which appeared to be a true effect and not age bias. Our study confirmed that the PEM is a reliable, valid and responsive instrument in assessing outcomes of disorders of the hand.

Abstract: The pathogenesis of all forms of psoriasis remains obscure. Segregation analysis and twin studies together with ethnic diVerences in disease frequency all point to an underlying genetic susceptibility to psoriasis, which is both complex and likely to reflect the action of a number of genes. We performed a genome wide analysis using a total of 271 polymorphic autosomal markers on 284 sib relative pairs identified within 158 independent families. We detected evidence for linkage at 6p21 (PSORS1) with a non-parametric linkage score (NPL)=4.7, p=2 × 10 -6 and at chromosome 1p (NPL=3.6, p=1.9 × 10 -4 ) in all families studied. Significant excess (p=0.004) paternal allele sharing was detected for markers spanning the PSORS1 locus. A further three regions reached NPL scores of 2 or greater, including a region at chromosome 7 (NPL 2.1),for which linkage for a number of autoimmune disorders has been reported.Partitioning of the data set according to allele sharing at 6p21 (PSORS1) favoured linkage to chromosomes 2p (NPL 2.09) and 14q (NPL 2.0), both regions implicated in previous independent genome scans, and suggests evidence for epistasis between PSORS1 and genes at other genomic locations. This study has provided linkage evidence in favour of a novel susceptibility locus for psoriasis and provides evidence of the complex mechanisms underlying the genetic predisposition to this common skin disease. (J Med Genet 2001;38:7‐13)

Abstract: The performance of ruthenium-tin catalysts for the liquid phase selective hydrogenation of oleic acid to unsaturated alcohols has been investigated. Titania-supported ruthenium and ruthenium-tin catalysts prepared by conventional impregnation as well as alumina-supported sol–gel ruthenium and ruthenium-tin catalysts have been used. The hydrogenation over the monometallic ruthenium catalysts leads primarily to the saturated stearic acid, which is then consecutively hydrogenated to the saturated stearyl alcohol. The titania-supported monometallic ruthenium catalyst shows a greater activity than the alumina-supported sol–gel one for the hydrogenation of oleic acid to the saturated stearyl alcohol. The hydrogenation over the bimetallic ruthenium-tin catalysts is characterized by the near total suppression of the hydrogenation of the olefine bond in favor of the activation of the hydrogenation of the carboxylic bond, thus leading to the selective formation of unsaturated alcohols. Besides, these catalysts are active for the cis–trans isomerization reaction of the oleic acid to elaidic acid, in competition with the hydrogenation of the carboxylic group. The impregnated titania-supported ruthenium-tin catalyst shows a better performance than the alumina-supported sol–gel ruthenium-tin catalyst for the selective hydrogenation of oleic acid to unsaturated alcohols.

Abstract: Filtered back-projection (FBP) is the most commonly used reconstruction method for PET images, which are usually noisy. The iterative reconstruction segmented attenuation correction (IRSAC) algorithm improves image quality without reducing image resolution. The standardized uptake value (SUV) is the most clinically utilized quantitative parameter of [fluorine-18]fluoro-2-deoxy-D-glucose (FDG) accumulation. The objective of this study was to obtain a table of SUVs for several normal anatomical structures from both routinely used FBP and IRSAC reconstructed images and to compare the data obtained with both methods. Twenty whole-body PET scans performed in consecutive patients with proven or suspected non-small cell lung cancer were retrospectively analyzed. Images were processed using both IRSAC and FBP algorithms. Nonquantitative or gaussian filters were used to smooth the transmission scan when using FBP or IRSAC algorithms, respectively. A phantom study was performed to evaluate the effect of different filters on SUV. Maximum and average SUVs (SUVmax and SUVavg) were calculated in 28 normal anatomical structures and in one pathological site. The phantom study showed that the use of a nonquantitative smoothing filter in the transmission scan results in a less accurate quantification and in a 20% underestimation of the actual measurement. Most anatomical structures were identified in all patients using the IRSAC images. On average, SUVavg and SUVmax measured on IRSAC images using a gaussian filter in the transmission scan were respectively 20% and 8% higher than the SUVs calculated from conventional FBP images. Scatterplots of the data values showed an overall strong relationship between IRSAC and FBP SUVs. Individual scatterplots of each site demonstrated a weaker relationship for lower SUVs and for SUVmax than for higher SUVs and SUVavg. A set of reference values was obtained for SUVmax and SUVavg of normal anatomical structures, calculated with both IRSAC and FBP image reconstruction algorithms. The use of IRSAC and a gaussian filter for the transmission scan seems to give more accurate SUVs than are obtained from conventional FBP images using a nonquantitative filter for the transmission scan.

Abstract: The Neotropical pitviper genus Bothrops comprises about 40 species, which occur in all main ecosystems of cis-Andean South America. We explored the relationships of body size and form (tail length and stoutness) with macrohabitat use in 20 forms of Bothrops. Semi-arboreal habits appeared only in forest forms. Semi-arboreals are significantly more slender and have longer tails than terrestrials; body size is not significantly different between terrestrials and semi-arboreals. Within Bothrops, independent contrasts for macrohabitat use were significantly correlated with contrasts of tail size (positively) and stoutness (negatively); thus, the more arboreal the species, the longer its tail and the more slender its body. Contrasts of adult body size seems to remain constant over the lower range of macrohabitat use, but to decrease in species of Bothrops which are more arboreal. Reconstructions of character states indicate that: (1) the ancestor of Bothrops was a small, stout, terrestrial species; (2) semi-arboreal habits appeared one to three times in the genus; (3) a decrease in stoutness and an increase in tail length occurred along with an increase in arboreality in some clades. Although macrohabitat use seems to be important in determining body form in Bothrops, our results also indicate that tail size, stoutness and body size may also be affected by selective agents other than macrohabitat use. The selective agents responsible for the shifts in macrohabitat use in Bothrops are still uncertain, although they may have included prey availability and/or predation pressure. The plasticity of macrohabitat use, morphology and body size described in this study may have been key features that facilitated the highly successful ecological diversification of Bothrops in South America.

Abstract: Although there has been substantial research using long-run co-movement (cointegration) restrictions in the empirical macroeconomics literature, little or no work has been done investigating the existence of short-run co-movement (common cycles) restrictions and discussing their implications. In this paper we first investigate the existence of common cycles in a aggregate data set comprising per-capita output, consumption, and investment. Later we discuss their usefulness in measuring the relative importance of transitory shocks. We show that, taking into account common-cycle restrictions, transitory shocks are more important than previously thought at business-cycle horizons. The central argument relies on efficiency gains from imposing these short-run restrictions on the estimation of the dynamic model. Finally, we discuss how the evidence here and elsewhere can be interpreted to support the view that nominal shocks may be important in the short run.

Abstract: The synthesis and characterisation of 2,6-bis(imino)pyridyl iron and cobalt complexes [(2,6-(RNCMe)2C5H3N)MCl2] containing nitrogen substituents of the type R = NPh2, NPhMe, NMe2 or 2,5-dimethylpyrrolyl are described. These complexes, in combination with the co-catalyst MAO, give active catalysts for the oligomerisation or polymerisation of ethylene. The catalytic activity is strongly affected by the substituents R and the polymerisation conditions used. The polymer properties are also a function of the R substituents. With R = NPhMe or NMe2, toluene soluble α-olefins are obtained, whereas the bulkier substituents (R = NPh2 or 2,5-dimethylpyrrolyl) give low molecular weight solid polyethylene.

Abstract: Purpose To evaluate the microhardness of enamel treated with two different 10% carbamide peroxide bleaching materials at different time intervals. Materials and methods Two bleaching agents were analyzed: Opalescence (OPA) and Rembrandt (REM). The control group (CON) consisted of dental fragments maintained in artificial saliva. Bleaching was accomplished for 8 hrs per day and stored during the remaining time in an individual recipient with artificial saliva. Enamel microhardness testing was performed before the initial exposure to the treatments and after 1, 7, 14, 21, 28, 35 and 42 days. Results The ANOVA, followed by the Bartlet and Tukey tests, showed significant differences for treatments (P CON = REM). From the 21st-35th day, enamel fragments bleached with OPA and REM presented a decrease of microhardness. Statistical differences of microhardness were verified among all the treatments (OPA > CON > REM). On the day 42, statistical differences were not found between OPA and the control group, but they were found between REM and the control group (OPA = CON > REM). The polynomial regression showed an increase of microhardness for OPA until the 21st day, followed by a decrease of microhardness up to the 42nd day. A decrease of microhardness for REM was verified. There were alterations in enamel microhardness as a function of bleaching time when using the two different 10% carbamide peroxide whiteners. Over a 42-day treatment time, bleaching with REM agent caused a decrease in enamel microhardness. The OPA agent initially increased the microhardness, then returned to the control level. Different bleaching materials with the same concentration of carbamide peroxide have different effects on the enamel.

Abstract: BACKGROUND In quality improvement activities such as audit, some general practices succeed in improving care and some do not. With audit of care likely to be one of the major tools in clinical governance, it would be helpful to establish what features of primary health care teams are associated with successful audit in general practice. OBJECTIVE The aim of the present study was to identify those features of primary health care teams that were associated with successful quality improvement during systematic audit of diabetes care. METHOD Semi-structured tape-recorded interviews were carried out with lead GPs and practice nurses in 18 general practices in Leicestershire that had the opportunity to improve their care and had completed two data collections in a multipractice audit of diabetes care. The interviewees were asked to describe their practice's approach to audit and the transcripts were coded for common features and judged for strength of feeling by blinded independent raters. Features common to practices that had, and those that had not, managed to improve diabetes care were identified. RESULTS Six features were identified reliably in the transcripts by blinded independent raters. Four were significantly associated with the successful improvement of care. Success was more likely in teams in which: the GP or nurse felt personally involved in the audit; they perceived their teamwork as good; they had recognized the need for systematic plans to address obstacles to quality improvement; and their teams had a positive attitude to continued monitoring of care. A positive attitude to audit and a personal interest in the disease were not associated with improvement in care. CONCLUSIONS Success in improving diabetes care is associated with certain organizational features of primary health care teams. Experimental studies are required to determine whether the development of teamwork enables practice teams to identify and overcome systematically the obstacles to improved quality of patient care that face them.

Abstract: Objectives. To assess the levels of caveolin-1 in a series of bladder tumor specimens of varying stage and grade and to identify possible links between caveolin-1 status and clinical behavior. Caveolae have emerged as sites of important regulatory events at the cell membrane in many different cell types. Caveolins are the main structural components of caveolae and belong to a family of highly conserved integral membrane proteins. The function of caveolin-1 appears to be intrinsically linked to cell signaling modulation by multiple pathways. Modification of CAV-1 gene expression appears to be a common feature of the oncogenically transformed phenotype. Methods. Using a rabbit polyclonal antibody against caveolin-1 and immunohistochemistry, we assessed caveolin-1 protein expression in 89 formalin-fixed, paraffin-embedded bladder tumor sections. The patient group studied included 71 men and 18 women (mean age ± SD 69.7 ± 10.9 years). The stage was Ta-T1 in 68 and T2-T4 in 21 tumors in this series. The clinical follow-up was 1 to 38 months (mean 21.2 ± 9.9). Results. A statistically significant association was observed between caveolin-1 immunoreactivity and tumor grade ( P = 0.0118, chi-square test), with 8 (21%) of 38 G3, 1 (3%) of 30 G2, and 0 of 21 G1 tumors positive for caveolin-1. When the clinical data were examined in conjunction with caveolin-1 status, no statistically significant relationship was seen between caveolin-1 expression and tumor multiplicity, tumor recurrence, tumor progression, or patient survival. Conclusions. The results of our study demonstrate that altered expression of caveolin-1 protein is a component of tumor dedifferentiation in a subset of high-grade bladder cancers. This pilot study provides a basis for further investigation of the role of caveolin-1 and the function of caveolae in the most aggressive forms of this tumor.

Abstract: BACKGROUND In a retrospective case-note and computer database analysis we assessed the outcome of very elderly patients (> or = 75 years old) with end-stage renal disease (ESRD) on renal replacement therapy (RRT). METHODS Fifty-eight individuals aged 75 or over (group 1) commenced RRT between 1 January 1991 and 31 December 1995. Comparisons were made with other patients commencing RRT who were divided into two groups: group 2 (201 individuals 65-74 years old) and group 3 (379 patients <65 years old). All subjects were followed up until the point of assessment (30 June 1998), the time of death, or withdrawal from dialysis. Survival rates in the three groups were compared using Kaplan-Meier method. The number of hospital admissions, length of in-patient stay, and complications rate on RRT were assessed for group 1. RESULTS One-year survival rates in groups 1, 2 and 3 were 53.5, 72.6, and 90.6% respectively and the 5-year survival rates were 2.4, 18.8, and 61.4% respectively. The very elderly spent 20% of their time in hospital, 46% had two co-morbid factors at the outset, and 26% developed multiple complications while on RRT. Withdrawal from dialysis remained the most common cause of death in this group of individuals (38%), followed by cardiovascular causes (24%) and infections (22%). CONCLUSION Very elderly ESRD patients on RRT have a very poor outcome and, since they are the largest growing group of RRT patients, this has important implications for future health policies.

Abstract: We investigate the wavelength-dependent intensity and reverberation properties of the UV-optical diffuse continuum emission expected from broad emission line gas. The "locally optimally emitting clouds" picture is adopted, with the cloud distribution functions in gas density and distance from the ionizing source determined by a fit to the mean UV emission-line spectrum from the 1993 HST campaign of NGC 5548 in our previous paper. The model Balmer continuum's strength and variability characteristics are in agreement with those derived from the observations of NGC 5548. A key prediction is a wavelength-dependent lag across the UV-optical spectrum that can broadly mimic the signature from X-ray reprocessing in an accretion disk, calling into question claims of discovery of the latter in NGC 7469. The influence of the diffuse continuum on the optical continuum may result in a small yet significant underestimation of the characteristic sizes of the regions emitting the optical emission lines. Its contribution can also alter the inferred spectral energy distribution of the UV-optical continuum, even well outside the spectral region near the well-known Balmer jump. The reverberation of the diffuse continuum emitted by the broad-line region may account for perhaps one-third of the observed effect that the λ1350-λ5100 continuum becomes bluer as it becomes brighter (even after accounting for nonvariable optical starlight). And as in other models of the broad emission line gas, a significant yet unobserved Lyman jump is predicted. We highlight the importance of careful studies of the UV-optical continuum, especially the Balmer continuum.

Abstract: In man, infertility is associated with microdeletions of specific regions of the long arm of the Y chromosome. This indicates that factors encoded by the Y chromosome are necessary for spermatogenesis. However, the majority of men with either idiopathic azoospermia or oligozoospermia have grossly intact Y chromosomes and the underlying causes of their infertility are unknown. We hypothesized that some of these individuals may carry other rearrangements or sequence variants on the non-recombining region of the Y chromosome that may be associated with reduced spermatogenesis. To test this hypothesis, we typed the Y chromosome in a group of Danish men with known sperm counts and compared the haplotype distribution with that of a group of unselected Danish males. We found that one class of Y chromosome, referred to as haplogroup 26+, was significantly overrepresented (27.9%; P < 0.001) in the group of men with either idiopathic oligozoospermia (defined as <20 x 10(6 )sperm/ml) or azoospermia compared to the control Danish male population (4.6%). This study defines, for the first time, a class of Y chromosome that is at risk for infertility in a European population. This observation suggests that selection may be indeed active on the Y chromosome, at least in the Danish population, raising the possibility that it could alter the pattern of Y chromosome haplotype distribution in the general population.

Abstract: OBJECTIVE: To analyze patterns of disease in a population of Brazilian patients with primary ankylosing spondylitis (AS). METHODS: Retrospective study (1988-98) analyzing 147 patients with a diagnosis of primary AS according to the modified New York criteria. Selected patients had complete clinical (initial symptom, axial and peripheral involvement, heel enthesitis, extraarticular manifestations) and radiological (sacroiliac, lumbar, thoracic, and cervical spine) investigations, and these data were compared with sex, race, age at onset, and HLA-B27. RESULTS: There was a predominance of men (84.4%), Caucasian race (75.5%), adult onset (> 16 years, 85%), and positive HLA-B27 (78.2%). Family history of AS was noted in 14.3% of the patients. Pure axial AS was observed in 37 patients (25.2%). The predominant initial symptoms were inflammatory low back pain (61.9%) and peripheral arthritis (22.4%). Thoracic and cervical spine involvement was noted in 70.1% of the patients; radiological findings included syndesmophytes in 46.9% and "bamboo spine" in 20.4% of patients. The extraaxial joints most frequently involved were: ankles (39.5%), hips (36.1%), knees (29.3%), shoulders (19%), and sternoclaviculars (14.3%); heel enthesitis was present in 22.4%. Acute anterior uveitis was noted in 14.3% of patients. Male sex was associated with involvement of thoracic spine (p = 0.002), cervical spine (p = 0.002), and hips (p = 0.042), whereas female sex was associated with sternoclavicular (p = 0.024) involvement. Caucasian race presented higher frequency of positive family history (p = 0.023); there was no statistical significance of clinical and radiological variables compared with African-Brazilians. Juvenile onset AS presented higher frequency of ankle (p = 0.012) and knee (p = 0.001) involvement, heel enthesitis (p = 0.001), and total hip replacement (p = 0.038), whereas adult onset was associated with thoracic (p = 0.026) and cervical spine (p = 0.026) involvement and positive family history (p = 0.044). Positive HLA-B27 was associated with ankle involvement (p = 0.007) and heel enthesitis (p = 0.013). CONCLUSION: In this population women showed a milder axial involvement, Caucasian race presented axial and peripheral involvement similar to African-Brazilians, juvenile onset AS was associated with articular involvement of the lower limbs, and positive HLA-B27 was associated with ankle involvement.

Abstract: This article aims to clarify two issues relating to stalking: how potential victims perceive the crime and the prevalence of stalking and stalking-related acts among the British female population. Three hundred forty-eight women were invited to classify which of a range of intrusive behaviors were exemplars of stalking. They were then asked to indicate whether they had first-hand experience of any of these behaviors and, if so, to describe the worst episode. Of the sample, 24% reported at least one incident of stalking. The women held clear ideas on what they felt did and did not constitute stalking behaviors. Cluster analyses provided subtypes of stalking behaviors as perceived by respondents and subtypes of actual stalking as experienced by the sample. The findings suggest that a final legislative definition of stalking may not be necessary and that the high prevalence rate requires serious academic and legal attention.

Abstract: Lysine has long been recognized as an essential amino acid for humans and the lack or low supply of this compound in the diet may lead to mental and physical handicaps. Since lysine is severely restricted in cereals, the most important staple food in the world, the understanding of its biological roles must be a major concern. Here we show that lysine is an important precursor for de novo synthesis of glutamate, the most significant excitatory neurotransmitter in the mammalian central nervous system. We also show that the synthesis of glutamate from lysine, which is carried out by the saccharopine pathway, is likely to take place in neurons.

Abstract: The genes at the INK4A/ARF locus at 9p21 are frequently involved in human cancer. Virtually all p16(INK4A) exon 2 (henceforth called p16) inactivation in pediatric acute lymphoblastic leukemia (ALL) occurs by gene deletion. The results of this study illustrate that real-time quantitative polymerase chain reaction is capable of detecting gene deletion in primary patient specimens with a precision not previously achieved by conventional methods. Importantly, this assay includes the detection of hemizygous deletions. The study revealed, strikingly, that the risk ratio for relapse for hemizygous deletion compared with no deletion was 6.558 (P =.00687) and for homozygous deletion was 11.558 (P =.000539). These results confirm and extend the authors' previous findings that homozygous deletion of p16 in pediatric ALL patients is an independent prognostic indicator of outcome from therapy.

Abstract: The tumour suppressor gene PTEN/MMAC1/TEP1 has been implicated in a variety of human cancers and several inherited hamartoma tumour syndromes, including Cowden syndrome, which has a high risk of breast and thyroid cancer. We have previously reported that overexpression of PTEN in MCF-7 breast cancer cells induces cell cycle arrest and apoptosis. In this study, we analysed PTEN status at both the structural and expression levels and explored PTEN's growth-suppressive effects on thyroid. We found that 1 of 10 thyroid cancer lines [follicular thyroid carcinoma FTC-133] had hemizygous deletion and a splice variant IVS4--19G-->A in the remaining allele. Four lines, including FTC-133, express PTEN mRNA at low levels. In general, PTEN protein levels correlated with mRNA levels, except for NPA87, which has low levels of transcript and relatively high levels of PTEN protein. Transient expression of PTEN in seven thyroid cancer cell lines resulted in G(1) arrest in two well differentiated papillary thyroid cancer lines (PTCs) and both G(1) arrest and cell death in the remaining five lines, including three FTCs, one poorly differentiated PTC and one undifferentiated thyroid cancer. The level of phosphorylated Akt was inversely correlated with the endogenous level of PTEN protein and overexpression of PTEN-blocked Akt phosphorylation in all cells analysed. Our results suggest that downregulation of PTEN expression at the mRNA level plays a role in PTEN inactivation in thyroid cancer and PTEN exerts its tumour-suppressive effect on thyroid cancer through the inhibition of cell cycle progression alone or both cell cycle progression and cell death.

Abstract: We present the discovery of the Optical Transient (OT) of the long{duration gamma-ray burst GRB 000926. The optical transient was detected independently with the Nordic Optical Telescope and at Calar Alto 22.2 hours after the burst. At this time the magnitude of the transient was R =1 9:36. The transient faded with ad ecay slope of about 1:7 during the rst two days after which the slope increased abruptly (within a few hours) to about 2:4. The light-curve started to flatten o after about a week indicating the presence of an underlying extended object. This object was detected in a deep image obtained one month after the GRB at R =2 3:87 0:15 and consists of several compact knots within about 5 arcsec. One of the knots is spatially coin- cident with the position of the OT and hence most likely belongs to the host galaxy. Higher resolution imaging is needed to resolve whether all the compact knots belong to the host galaxy or to several independent objects. In a separate paper we present a discussion of the optical spectrum of the OT, and its inferred redshift (Mller et al., in prep.).

Abstract: We present the results of a study of the variability of X-ray sources in the central 30' of the nearby Andromeda Galaxy (M 31) based on XMM-Newton Performance Verification observations. Two observations of this field, with a total exposure time of about 50 ks, were performed in June and December of 2000. We found 116 sources brighter than a limiting luminosity of 6 x 10(35) erg s(-1) (0.3-12 keV, d = 760 kpc). For the similar to 60 brightest sources, we searched for periodic and non-periodic variability; at least 15% of these sources appear to be variable on a time scale of several months. We discovered a new bright transient source similar to2.9' from the nucleus in the June observation; this source faded significantly and was no longer detected in December. The behaviour of the object is similar to a handful of Galactic LMXB transients, most of which are supposed to harbor black holes. We detected pulsations with a period of similar to 865 s from a source with a supersoft spectrum. The flux of this source decreased significantly between the two XMM observations. The detected period is unusually short and points to a rapidly spinning magnetized white dwarf. The high luminosity and transient nature of the source suggest its possible identification with classical or symbiotic nova, some of which were observed earlier as supersoft sources.

Abstract: The aim of the study was to analyse the 2-year follow-up of a series of patients with the diagnosis of undifferentiated spondyloarthropathy (uSpA). A prospective study was carried out analysing 68 patients with symptomatic uSpA who fulfilled the European Spondylarthropathy Study Group (ESSG) criteria for seronegative spondyloarthropathies (SpA) and were aged between 18 and 50 years. Inclusion criteria included inflammatory low back pain (ILBP) (without radiographic sacroiliitis), asymmetric oligoarthritis (predominantly affecting large joints in the lower limbs) and heel enthesopathies (Achilles tendinitis and/or plantar fasciitis). Imaging methods included pelvic radiography (at study entry and after 2 years) and calcaneal radiography (at study entry). There was a predominance of male gender (78%), caucasoid race (72%) and positive HLA-B27 (54%), with a mean age of 31 years and mean disease duration of 5 years. The first disease manifestations were ILBP (49%), asymmetric oligoarthritis (35%) and heel enthesopathies (16%). A positive family history of a definite SpA was mentioned by 9% of the patients. Seventeen patients (25%) scored 5 points in the Amor set of SpA criteria; logistic regression analysis showed that HLA-B27, heel enthesopathy and asymmetric oligoarthritis were significantly associated with Amor criteria > or = 6, whereas ILBP was associated with Amor criteria or = 6 (p=0.001). After a 2-year follow-up the following outcomes were observed: uSpA 75%; disease remission 13%; ankylosing spondylitis 10%; psoriatic arthritis 2%. Logistic regression analysis showed that buttock pain and positive HLA-B27 (trend) were statistically associated with progression to a definite SpA. In conclusion, uSpA can represent a provisional diagnosis in the group of SpA and a systematic follow-up is necessary in order to better establish the different patterns of the disease.

Abstract: Cyclooxygenases (COX) catalyse the oxygenation of arachidonic acid to prostaglandin (PG) endoperoxides. Activity of one of the COX isoforms, COX-2, results in production of prostaglandin E(2) (PGE(2)) via the endoperoxide PGH(2). COX-2 has been implicated in the pathogenesis of colorectal cancer. Malondialdehyde (MDA) is a mutagen produced by spontaneous and enzymatic breakdown of PGH(2). MDA reacts with DNA to form adducts, predominantly the pyrimidopurinone adduct of deoxyguanosine (M(1)G). Here the hypothesis was tested that COX-2 activity in human colon cells results in formation of MDA and generation of M(1)G adducts. M(1)G was detected in basal cultures of human non-malignant colon epithelial (HCEC) and malignant SW48, SW480, HT29 and HCA-7 colon cells, at levels from 77 to 148 adducts/10(8) nucleotides. Only HCA-7 and HT29 cells expressed COX-2 protein. Levels of M(1)G correlated significantly (r = 0.98, P < 0.001) with those of intracellular MDA determined colorimetrically in the four malignant cell types, but neither parameter correlated with expression of COX-2 or PG biosynthesis. Induction of COX-2 expression by phorbol 12-myristate 13-acetate in HCEC cells increased PGE(2) production 20-fold and MDA concentration 3-fold. Selective inhibition of COX-2 activity in HCA-7 cells by NS-398 significantly inhibited PGE(2) production, but altered neither MDA nor M(1)G levels. Malondialdehyde treatment of HCEC cells resulted in a doubling of M(1)G levels. These results show for the first time in human colon cells that COX-2 activity is associated with formation of the endogenous mutagen, MDA. Moreover, they demonstrate the correlation between MDA concentration and M(1)G adduct levels in malignant cells.

Abstract: Introduction The decline in heart-beating brainstem dead organ donors has necessitated the search for other organ sources. In the field of renal transplantation one alternative source currently available, but little used, is that of kidneys from non-heart-beating donors (NHBD). Reticence to use NHBD kidneys is in part due to concerns over the effect that warm ischemic may have subsequent graft function. Presented here are the results of the NHBD renal transplants at the Leicester transplant unit, and compared with matched heart-beating donor transplants as a case control analysis. Methods In order to analyze any differences in graft performance between the two organ sources, the confounding effect of other variables known to influence the outcome of renal transplantation was minimized by matching NHBD and HBD transplants for the following criteria: donor age and sex, first or re-transplant, anastomosis and cold times, tissue match and PRA sensitisation. Transplant performance was assessed primarily by graft survival, the statistical evaluation of which was by log rank analysis of Kaplan-Meier curves. Results 72 NHBD and 192 HBD transplants were performed over an eight year period. Of the 192 HBD transplants, 105 matched one or more of the NHBD by the criteria outlined above, and thus constituted the control group for comparison. There was no significant difference in overall graft survival between the two groups. The 5 year survival for the NHBD was 73% compared with 65% for HBD kidneys. When death with a functioning graft is treated as censored data, then these figures become 75% and 81% respectively, again without statistical significance. Conclusion NHBD kidneys are a valuable additional source of organs for transplantation, with long-term survival, comparable to transplants from HBD.