Evaluation of myosin VI, E-cadherin and beta-catenin immunostaining in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Renal cell carcinoma (RCC) is a cancer of increasing incidence and mortality. Currently, there are no immunohistochemical prognostic markers for RCCs in routine use. The aim of this study was to examine for the first time the immunostaining of myosin VI in RCCs as well as its association with E-cadherin and beta-catenin immunostaining and the prognostic significance of these markers in RCCs.</p> <p>Methods</p> <p>Our study population consisted of 152 patients who underwent surgery for RCCs between 1990 and 1999. The tumours were examined with three immunohistochemical markers: myosin VI, E-cadherin and beta-catenin.</p> <p>Results</p> <p>The immunostaining for cytoplasmic myosin VI was common (72%). One-third of the tumours were immunopositive for nuclear myosin VI. Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades (<it>p </it>= 0.04 and <it>p </it>= 0.005, respectively), but not stages. There was no significant association between myosin VI immunostaining and the histological subtype of RCC. Nuclear myosin VI was associated with the nuclear expression of beta-catenin. A direct association could also be proven between membranous E-cadherin and cytoplasmic beta-catenin. Cytoplasmic myosin VI immunostaining was a marker of poorer prognosis in multivariate Cox regression model adjusted with stage and Fuhrman grade with hazard ratio 2.4 (95% confidence interval 1.1 to 5.0 with <it>p </it>= 0.024).</p> <p>Conclusions</p> <p>Cytoplasmic myosin VI immunopositivity and nuclear beta-catenin immunostaining were associated with lower Fuhrman grades, and there was a strong positive relationship between E-cadherin immunostaining and beta-catenin immunostaining in RCCs. Cytoplasmic myosin VI immunostaining was associated with poorer prognosis in RCCs.</p

The effect of coating properties on the performance of a-C:H and ta-C films

DLC films cover a wide range of different carbon based coatings, starting from soft to extremely hard diamond-like carbon films. In this study two different types of DLC films have been studied in respect of their stress and strain characteristics and tribological performance. The coatings are hydrogenated amorphous carbon (a-C:H) coatings deposited by PECVD and tetrahedral amorphous carbon (ta-C) coating deposited by filtered arc technique. In order to evaluate the mechanical behaviour of the coatings under load, 3D FE modelling was carried out in combination with scratch testing. Also the tribological performance was evaluated with pin-on-disc tests using stepwise increasing normal load. The 3D FEM model was developed for calculating the stress and strain distributions of DLC coated systems and to evaluate how coating thickness and elastic properties affect the stress-strain state at crack initiation location. The simulation was compared to the findings to experimental observations in scratch test contact conditions, when the spherical diamond tip was moving with increased load on a coated surface. The coating performance was evaluated with scratch testing to detect the crack generation as well as the coating adhesion. When combining the simulated coating characteristics with empirical observation of coating fracture patterns the coating fracture performance and tolerance to cracking could be evaluated. A major effect of the coating elastic modulus on the stress and fracture behaviour of the coatings was observed. In the tribological testing the both coatings had a low friction performance. In the tribological testing with stepwise increasing load, the critical load for coating delamination was higher for the a-C:H coating, which is in accordance with the results of FE modelling of coating stress state

Multichannel optical sensor for oil film pressure measurement in engine main bearing

An optical sensor has been developed for experimental determination of oil film pressure in journal bearings. The non-intrusive fibre optic sensor is integrated in the sliding surface of the bearing to measure the actual oil film pressure under load without disturbing the actual tribological contact conditions. The sensors with a multichannel system also allowed the use of several optical sensors simultaneously. Four optical sensors were integrated in a hydrodynamic journal bearing of a large scale diesel engine and the engine tests were carried out with different loads to study the sensor operation in demanding operating conditions. The oil film pressure was successfully measured and the results showed differences in bearing pressure depending on the position of the sensor and on the operating cycle of the cylinders. The optical sensor was capable to measure the oil film pressure in journal bearing with a good sensitivity and repeatability during the tests. &nbsp

Cardiorespiratory Fitness Is Related to the Risk of Sudden Cardiac Death A Population-Based Follow-Up Study

ObjectivesOur aim was to examine the relation of cardiorespiratory fitness with sudden cardiac death (SCD) in a population-based sample of men.BackgroundVery limited information is available about the role of cardiorespiratory fitness in the prediction of SCD.MethodsThis population study was based on 2,368 men 42 to 60 years of age. Cardiorespiratory fitness was defined by using respiratory gas exchange analyzer and maximal workload during cycle ergometer exercise test.ResultsDuring the 17-year follow-up, there were 146 SCDs. As a continuous variable, 1 metabolic equivalent (MET) increment in cardiorespiratory fitness was related to a decrease of 22% in the risk of SCD (relative risk: 0.78, 95% confidence interval: 0.71 to 0.84, p < 0.001). In addition to cardiorespiratory fitness, ischemic ST-segment depression during exercise testing, smoking, systolic blood pressure, prevalent coronary heart disease, family history of coronary heart disease, and type 2 diabetes mellitus were related to the risk of SCD. The Harrell C-index for the total model discrimination was 0.767, while cardiorespiratory fitness provides modest improvement (from 0.760 to 0.767) in the risk prediction when added with all other risk factors. The integrated discrimination improvement was 0.0087 (p = 0.018, relative integrated discrimination improvement 0.11) when cardiorespiratory fitness was added in the model. However, the net reclassification index (−0.018) was not statistically significantly improved (p = 0.703).ConclusionsCardiorespiratory fitness is a predictor of SCD in addition to that predicted by conventional risk factors. There was a slight improvement in the level of discrimination, although the net reclassification index did not change while using cardiorespiratory fitness with conventional risk factors

Absent Toll-like receptor-9 expression predicts poor prognosis in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 9 (TLR9) is a cellular DNA-receptor whose activation with cognate ligands triggers an immune reaction, with increased production of inflammatory cytokines. The aim of this study was to examine the expression of TLR9 in renal cell carcinoma (RCC), which is generally renowned of its immunogenic nature. We also evaluated the prognostic value of TLR9 in RCC.</p> <p>Methods</p> <p>TLR9 expression in RCC was characterized with immunohistochemistry in a retrospective study population of 152 RCC patients who underwent renal surgery. The TLR9 staining intensity was compared with clinical parameters.</p> <p>Results</p> <p>Of the studied tumours, 112 (81%) exhibited cytoplasmic TLR9 immunostaining. No association was detected between cytoplasmic TLR9 immunoexpression intensity and stage, nuclear grade, histological subtype or tumour necrosis. Cytoplasmic TLR9 immunoexpression was, however, a marker of favourable RCC specific survival both in univariate analysis and in multivariate regression model.</p> <p>Conclusions</p> <p>We conclude that TLR9 expression is an independent prognostic marker of RCC and the absence of TLR9 expression is related to poorer prognosis in RCC.</p

Search for intracranial aneurysm susceptibility gene(s) using Finnish families

BACKGROUND: Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci. METHODS: We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect. RESULTS: Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6. CONCLUSIONS: Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests

Extremes on the discounted aggregate claims in a time dependent risk model

This paper presents an extension of the classical compound Poisson risk model for which the inter-claim time and the forthcoming claim amount are no longer independent random variables (rv's). Asymptotic tail probabilities for the discounted aggregate claims are presented when the force of interest is constant and the claim amounts are heavy tail distributed rv's. Furthermore, we derive asymptotic finite time ruin probabilities, as well as asymptotic approximations for some common risk measures associated with the discounted aggregate claims. A simulation study is performed in order to validate the results obtained in the free interest risk model

Cosmological Backreaction from Perturbations

We reformulate the averaged Einstein equations in a form suitable for use with Newtonian gauge linear perturbation theory and track the size of the modifications to standard Robertson-Walker evolution on the largest scales as a function of redshift for both Einstein de-Sitter and Lambda CDM cosmologies. In both cases the effective energy density arising from linear perturbations is of the order of 10^-5 the matter density, as would be expected, with an effective equation of state w ~ -1/19. Employing a modified Halofit code to extend our results to quasilinear scales, we find that, while larger, the deviations from Robertson-Walker behaviour remain of the order of 10^-5.Comment: 15 pages, 8 figures; replaced by version accepted by JCA