Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum) levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate. METHODS: MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis. RESULTS: Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 ± 3.91 ng/ml; ± interquartile range; n = 115) compared with patients with no documented diagnosis of prostate cancer (2.19 ± 2.65 ng/ml; n = 158). ELISA diluent reagents that included bovine serum albumin (BSA) significantly reduced MIF serum detection (p < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but cancer showed statistically greater MIF expression. MIF and its receptor (CD74) were localized to prostatic epithelium. Increased secreted MIF was detected in culture medium from prostate cancer cell lines (LNCaP and PC-3). CONCLUSION: Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot) found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer

Spitzer 24 micron Survey of Debris Disks in the Pleiades

We performed a 24 micron 2 Deg X 1 Deg survey of the Pleiades cluster, using the MIPS instrument on Spitzer. Fifty four members ranging in spectral type from B8 to K6 show 24 micron fluxes consistent with bare photospheres. All Be stars show excesses attributed to free-free emission in their gaseous envelopes. Five early-type stars and four solar-type stars show excesses indicative of debris disks. We find a debris disk fraction of 25 % for B-A members and 10 % for F-K3 ones. These fractions appear intermediate between those for younger clusters and for the older field stars. They indicate a decay with age of the frequency of the dust-production events inside the planetary zone, with similar time scales for solar-mass stars as have been found previously for A-stars.Comment: accepted to Ap

Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

BACKGROUND: The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. METHODS: MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. RESULTS: Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. CONCLUSIONS: This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

Adults’ number-line estimation strategies: Evidence from eye movements

Although the development of number-line estimation ability is well documented, little is known of the processes underlying successful estimators’ mappings of numerical information onto spatial representations during these tasks. We tracked adults’ eye movements during a number-line estimation task to investigate the processes underlying number-to-space translation, with three main results. First, eye movements were strongly related to the target number’s location, and early processing measures directly predicted later estimation performance. Second, fixations and estimates were influenced by the size of the first number presented, indicating that adults calibrate their estimates online. Third, adults’ number-line estimates demonstrated patterns of error consistent with the predictions of psychophysical models of proportion estimation, and eye movement data predicted the specific error patterns we observed. These results support proportion-based accounts of number-line estimation and suggest that adults’ translation of numerical information into spatial representations is a rapid, online process

Ruthenium-based PACT agents based on bisquinoline chelates: synthesis, photochemistry, and cytotoxicity

The known ruthenium complex [Ru(tpy)(bpy)(Hmte)](PF6)(2) ([1](PF6)(2), where tpy = 2,2':6',2 ''-terpyridine, bpy = 2,2'-bipyridine, Hmte = 2-(methylthio)ethanol) is photosubstitutionally active but non-toxic to cancer cells even upon light irradiation. In this work, the two analogs complexes [Ru(tpy)(NN)(Hmte)](PF6)(2), where NN = 3,3'-biisoquinoline (i-biq, [2](PF6)(2)) and di(isoquinolin-3-yl)amine (i-Hdiqa, [3](PF6)(2)), were synthesized and their photochemistry and phototoxicity evaluated to assess their suitability as photoactivated chemotherapy (PACT) agents. The increase of the aromatic surface of [2](PF6)(2) and [3](PF6)(2), compared to [1](PF6)(2), leads to higher lipophilicity and higher cellular uptake for the former complexes. Such improved uptake is directly correlated to the cytotoxicity of these compounds in the dark: while [2](PF6)(2) and [3](PF6)(2) showed low EC50 values in human cancer cells, [1](PF6)(2) is not cytotoxic due to poor cellular uptake. While stable in the dark, all complexes substituted the protecting thioether ligand upon light irradiation (520 nm), with the highest photosubstitution quantum yield found for [3](PF6)(2) (phi([3]) = 0.070). Compounds [2](PF6)(2) and [3](PF6)(2) were found both more cytotoxic after light activation than in the dark, with a photo index of 4. Considering the very low singlet oxygen quantum yields of these compounds, and the lack of cytotoxicity of the photoreleased Hmte thioether ligand, it can be concluded that the toxicity observed after light activation is due to the photoreleased aqua complexes [Ru(tpy)(NN)(OH2)](2+), and thus that [2](PF6)(2) and [3](PF6)(2) are promising PACT candidates.[GRAPHICS].Metals in Catalysis, Biomimetics & Inorganic Material

Systolic Blood Pressure, Socioeconomic Status, and Biobehavioral Risk Factors in a Nationally Representative US Young Adult Sample

In the National Longitudinal Study of Adolescent Health, a US longitudinal study of over 15,000 young adults, we examined the extent to which socioeconomic status is linked to systolic blood pressure, and whether biobehavioral risk factors mediate the association. Over 62% of the participants had systolic blood pressure >120 mmHg and 12% with systolic blood pressure >140 mmHg. Over 66% were classified as at least overweight (Body Mass Index>25 kg/m2), with over 36% meeting criteria for at least Class I obesity (Body Mass Index>30 kg/m2). Multivariate models showed that higher household income and being married were independently associated with lower systolic blood pressure. Higher body mass index, greater waist circumference, smoking, and higher alcohol intake were each independently associated with higher systolic blood pressure. Meditational analyses suggested that higher education level was associated with lower systolic blood pressure by way of lower body mass, smaller waist circumference, and lower resting heart rate. When these indirect effects were accounted for, education was not significantly associated with systolic blood pressure. In contrast, household income remained associated with systolic blood pressure even with control for all covariates. Results reinforce current public health concerns about rates of obesity and high blood pressure among young adults and suggest that disparities in education level and household income may play an important role the observed decrements in health. Identifying modifiable mechanisms that link socioeconomic status to systolic blood pressure using data from a large representative sample may improve risk stratification and guide the development of effective interventions

High accuracy 234U(n,f) cross section in the resonance energy region

New results are presented of the 234U neutron-induced fission cross section, obtained with high accuracy in the resonance region by means of two methods using the 235U(n,f) as reference. The recent evaluation of the 235U(n,f) obtained with SAMMY by L. C. Leal et al. (these Proceedings), based on previous n-TOF data [1], has been used to calculate the 234U(n,f) cross section through the 234U/235U ratio, being here compared with the results obtained by using the n-TOF neutron flux

Measurement of the 240Pu(n,f) cross-section at the CERN n-TOF facility : First results from experimental area II (EAR-2)

The accurate knowledge of the neutron-induced fission cross-sections of actinides and other isotopes involved in the nuclear fuel cycle is essential for the design of advanced nuclear systems, such as Generation-IV nuclear reactors. Such experimental data can also provide the necessary feedback for the adjustment of nuclear model parameters used in the evaluation process, resulting in the further development of nuclear fission models. In the present work, the 240Pu(n,f) cross-section was measured at CERN's n-TOF facility relative to the well-known 235U(n,f) cross section, over a wide range of neutron energies, from meV to almost MeV, using the time-of-flight technique and a set-up based on Micromegas detectors. This measurement was the first experiment to be performed at n-TOF's new experimental area (EAR-2), which offers a significantly higher neutron flux compared to the already existing experimental area (EAR-1). Preliminary results as well as the experimental procedure, including a description of the facility and the data handling and analysis, are presented

The measurement programme at the neutron time-of-flight facility n-TOF at CERN

Neutron-induced reaction cross sections are important for a wide variety of research fields ranging from the study of nuclear level densities, nucleosynthesis to applications of nuclear technology like design, and criticality and safety assessment of existing and future nuclear reactors, radiation dosimetry, medical applications, nuclear waste transmutation, accelerator-driven systems and fuel cycle investigations. Simulations and calculations of nuclear technology applications largely rely on evaluated nuclear data libraries. The evaluations in these libraries are based both on experimental data and theoretical models. CERN's neutron time-of-flight facility n-TOF has produced a considerable amount of experimental data since it has become fully operational with the start of its scientific measurement programme in 2001. While for a long period a single measurement station (EAR1) located at 185 m from the neutron production target was available, the construction of a second beam line at 20 m (EAR2) in 2014 has substantially increased the measurement capabilities of the facility. An outline of the experimental nuclear data activities at n-TOF will be presented