DEVELOPMENTAL DYNAMICS, Issue 4 2004
Athanasios K. Petridis
Abstract Expression of polysialic acid (PSA) promotes migration of progenitor cells from the subventricular zone (SVZ) to the olfactory bulb, where they differentiate into interneurons. This differentiation has been found to coincide with a loss of PSA. Moreover, specific removal of PSA from the mouse SVZ by endoneuraminidase-N was found to cause premature differentiation, as evidenced by neurite outgrowth and tyrosine hydroxylase synthesis in vivo and by expression of neurofilament-L and ,III-tubulin in SVZ explant cultures. This differentiation involved activation of mitogen-activated protein kinase through p59fyn and was blocked by its inhibition. The effects of PSA removal were found to be cell contact-dependent and to be reduced by anti,neural cell adhesion molecule antibodies. These findings indicate that PSA expression regulates the fate of SVZ precursors by two contact-dependent mechanisms, the previously reported reduction in cell,cell adhesion that allows cell translocation, and the postponement of cell differentiation that otherwise would be induced by signals generated through surface molecule-mediated cell,cell interactions. Developmental Dynamics 230:675,684, 2004. © 2004 Wiley-Liss, Inc. [source]

Evidence-based guidelines to optimize the selection of antibody panels in cytopathology: Pleural effusions with malignant epithelioid cells

DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2010
Danielle E. Westfall M.D.
Abstract There is no established methodology to help select cost effective antibody panels. We used Bayesian statistics and an evidence-based pathology (EBP) approach to retrospectively review the use of immunohistochemistry (IHC) in 153 consecutive pleural effusions evaluated in our laboratory from 2005,2007 for the differential diagnosis of malignant mesothelial cells versus carcinoma cells and to estimate the likely site of origin of a carcinoma. The results in this "training" set were used to design antibody panels and test their clinical applicability on a "test set" of 44 pleural effusions collected in early 2008. Cytopathologists had used 6 ± 4.5 IHC tests per case for the diagnosis of malignant mesothelioma (n = 9) and carcinomas of lung (n = 60), breast (n = 47), Müllerian (n = 25), and other origins in the "training set". The sensitivity and specificity of pleural cytology using all these IHC tests were 32% and 95%, respectively. Sensitivity, specificity and post-test odds (PTO) of a positive IHC result were calculated for each antibody and by the following classes: malignant mesothelial cells and carcinoma cells by primary site of origin. The antibodies that provided the best PTO to diagnose the most prevalent tumors in our population were included in diagnostic panels for male (calretinin, TTF-1, PSA and CDX-2) and female (calretinin, TTF-1, ER and CA125) patients. These panels provided 100% specificity and 77% and 50% sensitivity, respectively, for the pleural effusions from female and male patients in the "test set." The use of an EBP approach for test selection in cytopathology is discussed. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source]

Secondary prostatic adenocarcinoma: A cytopathological study of 50 cases

DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2007
F.R.C.P.C., Kien T. Mai M.D.
Abstract Positive diagnosis of metastatic prostate adenocarcinoma (PAC) can be made by microscopic examination of the cytologic specimens and immunostaining for prostate-specific antigen (PSA) and prostate acid phosphatase (PAP). Immunohistochemical markers have been known to display negative, weak, or focal staining in poorly differentiated PAC and in patients with prior hormonal and/or radiation therapy. The purpose of this study is to characterize the cytopathology of metastatic PAC as it has not been documented in large series. Fifty cases of metastatic PAC with cytological specimens consisting of 41 fine-needle aspiration biopsies (FNAB), 6 pleural fluid aspirates, and 3 catheterized urine samples were reviewed and correlated with the surgical specimens and the clinical charts. Immunostaining for PSA, PAP, cytokeratin AE1/3, cytokeratin 7 (CK7), cytokeratin 20 (CK20), vimentin, and carcinoembryonic antigen (CEA) was done. Mean patient age was 77 ± 8 yr; serum PSA, 4.1 ± 2.3; and primary PAC Gleason score, 8.1 ± 1.5. Cytologically, the specimens consisted of cell clusters or cell sheets with overlapping uniform hyperchromatic nuclei with or without nucleoli. Twelve cases were not reactive to PSA and PAP and 44 cases displayed negative immunoreactivity to both CK7 and CK20. Carcinoid-like lesions and small cell carcinomas were seen in 4 cases and were misdiagnosed as nonprostatic origin based on the following features: negative immunoreactivity to PSA and PAP with or without positive reactivity to CEA, and different histopathological features when compared with the primary PAC. In addition to the frequency of high-grade PAC, awareness of the negative immunoreactivity to PSA and PAP, the discrepancy in the histopathological patterns between the primary and secondary tumors, especially the frequent neuroendocrine differentiation, are helpful features for the diagnosis of metastases of prostatic origin. Diagn. Cytopathol. 2007;35:91,95. © 2007 Wiley-Liss, Inc. [source]

Wavelet-based simulation of spectrum-compatible aftershock accelerograms

EARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 11 2008
S. Das
Abstract In damage-based seismic design it is desirable to account for the ability of aftershocks to cause further damage to an already damaged structure due to the main shock. Availability of recorded or simulated aftershock accelerograms is a critical component in the non-linear time-history analyses required for this purpose, and simulation of realistic accelerograms is therefore going to be the need of the profession for a long time to come. This paper attempts wavelet-based simulation of aftershock accelerograms for two scenarios. In the first scenario, recorded main shock and aftershock accelerograms are available along with the pseudo-spectral acceleration (PSA) spectrum of the anticipated main shock motion, and an accelerogram has been simulated for the anticipated aftershock motion such that it incorporates temporal features of the recorded aftershock accelerogram. In the second scenario, a recorded main shock accelerogram is available along with the PSA spectrum of the anticipated main shock motion and PSA spectrum and strong motion duration of the anticipated aftershock motion. Here, the accelerogram for the anticipated aftershock motion has been simulated assuming that temporal features of the main shock accelerogram are replicated in the aftershock accelerograms at the same site. The proposed algorithms have been illustrated with the help of the main shock and aftershock accelerograms recorded for the 1999 Chi,Chi earthquake. It has been shown that the proposed algorithm for the second scenario leads to useful results even when the main shock and aftershock accelerograms do not share the same temporal features, as long as strong motion duration of the anticipated aftershock motion is properly estimated. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Estimation of strength reduction factors via normalized pseudo-acceleration response spectrum

EARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 6 2007
Debasis Karmakar
Abstract Estimation of design forces in ductility-based earthquake-resistant design continues to be carried out with the application of response modification factors on elastic design spectra, and it remains interesting to explore how best to estimate strength reduction factors (SRFs) for a design situation. This paper considers the relatively less explored alternative of modelling SRF spectrum via a given response spectrum. A new model is proposed to estimate the SRF spectrum in terms of a pseudo-spectral acceleration (PSA) spectrum and ductility demand ratio with the help of two coefficients. The proposed model is illustrated for an elasto-plastic oscillator, in case of 10 recorded accelerograms and three ductility ratios. The proposed model is convenient and is able to predict SRF spectrum reasonably well, particularly at periods up to 1.0 s. Coefficients of the proposed model may also be determined in case of a given design spectrum when there is uncertainty in SRF spectrum due to uncertainty in temporal characteristics of the ground motion. This is illustrated with the help of 474 accelerograms recorded in western U.S.A. and different scaled PSA spectra. It is shown that probabilistic estimates may be obtained in this situation for SRF spectrum by assuming the error residuals to be log normally distributed with period-dependent parameters. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Electrochemical Biosensor for the Detection of Interaction Between Arsenic Trioxide and DNA Based on Guanine Signal

ELECTROANALYSIS, Issue 7 2003
Mehmet Ozsoz
Abstract The interaction of arsenic trioxide (As2O3) with calf thymus double-stranded DNA (dsDNA), calf thymus single-stranded DNA (ssDNA) and also 17-mer short oligonucleotide (Probe,A) was studied electrochemically by using differential pulse voltammetry (DPV) with carbon paste electrode (CPE) at the surface and also in solution. Potentiometric stripping analysis (PSA) was employed to monitor the interaction of As2O3 with dsDNA in solution phase by using a renewable pencil graphite electrode (PGE). The changes in the experimental parameters such as the concentration of As2O3, and the accumulation time of As2O3 were studied by using DPV; in addition, the reproducibility data for the interaction between DNA and As2O3 was determined by using both electrochemical techniques. After the interaction of As2O3 with dsDNA, the DPV signal of guanine was found to be decreasing when the accumulation time and the concentration of As2O3 were increased. Similar DPV results were also found with ssDNA and oligonucleotide. PSA results observed at a low DNA concentration such as 1,ppm and a different working electrode such as PGE showed that there could be damage to guanine bases. The partition coefficients of As2O3 after interaction with dsDNA and ssDNA in solution by using CPE were calculated. Similarly, the partition coefficients (PC) of As2O3 after interaction with dsDNA in solution was also calculated by PSA at PGE. The features of this proposed method for the detection of DNA damage by As2O3 are discussed and compared with those methods previously reported for the other type of DNA targeted agents in the literature. [source]

Rapidly profiling blood,brain barrier penetration with liposome EKC

ELECTROPHORESIS, Issue 14 2007
Yongjun Wang
Abstract This report intended to study the potential of liposome EKC (LEKC) as a convenient and high-throughput screening tool to assess drug penetration across the blood,brain barrier (BBB). The retention factors (k) of 24 structurally diverse compounds were determined with LEKC and vesicle EKC (VEKC), respectively. Principal component analysis of the steady-state concentrations ratio of compounds in the brain and in the blood expressed as log,BB, log,kLEKC, log,kVEKC, and other lipophilic descriptors including octanol/water partition coefficient (Clog,P), octanol/water distribution coefficients (log,D7.4), and polar surface area (PSA), showed the maximum similarity of partitioning processes in LEKC to drug penetration across the BBB. Furthermore, the log,BB were correlated with the above five lipophilic descriptors, and the results showed that log,kLEKC gave the better correlation coefficient (r2,=,0.811, p <0.0001) than those of log,D7.4, Clog,P, PSA, and log,kVEKC (r2,=,0.730, 0.672, 0.627, and 0.620, p <0.0001). This is the first report of the use of LEKC as a promising rapid tool to profile drug penetration across the BBB. [source]

Integrated selective enrichment target , a microtechnology platform for matrix-assisted laser desorption/ionization-mass spectrometry applied on protein biomarkers in prostate diseases

ELECTROPHORESIS, Issue 21-22 2004
Simon Ekström
Abstract The performance of a miniaturized sample processing platform for matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS), manufactured by silicon microfabrication, called integrated selective enrichment target (ISET) technology was evaluated in a biological context. The ISET serves as both sample treatment device and MALDI-MS target, and contains an array of 96 perforated nanovials, which each can be filled with 40 nL of reversed-phase beads. This methodology minimizes the number of sample transfers and the total surface area available for undesired adsorption of the analytes in order to provide high-sensitivity analysis. ISET technology was successfully applied for characterization of proteins coisolated by affinity chromatography of prostate-specific antigen (PSA) from human seminal fluid. The application of ISET sample preparation enabled multiple analyses to be performed on a limited sample volume, which resulted in the discovery that prolactin inducible protein (PIP) was coisolated from the samples. [source]

High levels of serum prostate-specific antigen due to PSA producing follicular non-Hodgkin's lymphoma

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007
Jan Jelrik Oosterheert
Abstract Objective:, Both carcinoma of the prostate and non-Hodgkin's lymphoma are common in elderly patients. Measurement of serum prostate-specific antigen (PSA) is a frequently used tool to diagnose and monitor prostate carcinoma and is generally specific for diseases of the prostate. Case:, We describe a 68-yr-old patient with voiding difficulties and high PSA levels, but without inflammatory or malignant changes upon multiple transrectal ultrasound guided prostate biopsies. Digital rectal examination was normal. Laboratory showed a strongly elevated PSA level (62 ,g/L, Immulight 2000®; DPC, USA). A CT-scan showed a retroperitoneal process with mass in the right pelvis and infiltration of the bladder wall, suggestive for metastatic prostate carcinoma. Surgical excision of an axillary lymph node set the diagnosis at a stage IV follicular lymphoma, Berard grade I to II in which the majority of neoplastic cells expressed PSA. After lymphoma-specific treatment, there was a positron emission tomography (PET) confirmed complete remission with normal PSA levels (6 ,g/L), which still persists. Conclusion:, Although rare, high PSA levels can be due to the presence of non-Hodgkin's lymphoma. Such a diagnosis should be considered when patients present with lymphadenopathy other than regional prostatic lymphadenopathy. [source]

Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patients

EUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2007
P. Cortelli
The objective of this study was to determine the cardiovascular effects of chronic stimulation of the posterior hypothalamic area (PHA) in cluster headache (CH) patients. Systolic and diastolic blood pressure (SBP, DBP), cardiac output, total peripheral resistance (TPR), heart rate (HR) and breathing were monitored at supine rest and during head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing, cold face test and isometric handgrip in eight drug-resistant chronic CH patients who underwent monolateral electrode implantation in the PHA for therapeutic purposes. Autoregressive power spectral analysis (PSA) of HR variability (HRV) was calculated at rest and during HUTT. Each subject was studied before surgery (condition A) and after chronic deep brain stimulation (DBS) of PHA (condition B). Baseline SBP, DBP, HR and cardiovascular reflexes were normal and similar in both conditions. With respect to condition A, DBP, TPR and the LF/HF obtained from the PSA of HRV were significantly (P < 0.05) increased during HUTT in condition B. In conclusion, chronic DBS of the PHA in chronic CH patients is associated with an enhanced sympathoexcitatory drive on the cardiovascular system during HUTT. [source]

Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2000
J. Joaquín Merino
Abstract Cell adhesion molecules (CAMs) of the immunoglobulin superfamily, NCAM and L1, as well as the post-translational addition of ,-2,8-linked polysialic acid (PSA) homopolymers to NCAM (PSA,NCAM), have been implicated in the neural mechanisms underlying memory formation. Given that the degree of stress elicited by the training situation is one of the key factors that influence consolidation processes, this study questioned whether training rats under different stressor intensities (0.2, 0.4, or 1 mA shock intensity) in a contextual fear conditioning task might regulate subsequent expression of NCAM, PSA,NCAM and L1 in the hippocampus, as evaluated immediately after testing rats for conditioning at 12 and 24 h after training. Behavioural inhibition (evaluated as a ,freezing' index) at testing and post-testing plasma corticosterone levels were also assessed. The results showed that 12 h post-training, conditioned animals displayed reduced NCAM, but increased L1, expression. At this time point, the group trained at the highest shock intensity (1 mA) also presented decreased PSA,NCAM expression. Analyses performed 24 h post-training indicated that the 1 mA group exhibited increased NCAM and L1 expression, but decreased expression of PSA,NCAM levels. In addition, L1 values that presented a shock intensity-dependent U-shaped pattern were also increased in the group trained at the lowest shock condition (0.2 mA) and remained unchanged in the intermediate shock condition (0.4 mA). Freezing and corticosterone values at both testing times were positively related with shock intensity experienced at training. Therefore, our results show a complex regulation of CAMs of the immunoglobulin superfamily in the hippocampus that depends upon stressor intensity and time factors. In addition, the pattern of CAMs expression found in the 1 mA group (which is the one that shows higher post-training corticosterone levels and develops the stronger and longer-lasting levels of fear conditioning) supports the view that, after a first phase of synaptic de-adherence during consolidation, NCAM and L1 might participate in the stabilization of selected synapses underlying the establishment of long-term memory for contextual fear conditioning, and suggests that glucocorticoids might play a role in the observed regulation of CAMs. [source]

Multifunctional Microporous MOFs Exhibiting Gas/Hydrocarbon Adsorption Selectivity, Separation Capability and Three-Dimensional Magnetic Ordering,

ADVANCED FUNCTIONAL MATERIALS, Issue 15 2008
Kunhao Li
Abstract Microporous materials [M3(HCOO)6],·,DMF (M,=,Mn, Co, Ni) were synthesized solvothermally and structurally characterized by single crystal and powder X-ray diffraction methods. The metal network exhibits diamondoid connectivity and the overall framework gives rise to zigzag channels along the b axis where guest dimethylformamide molecules reside. The effective pore size of these channels is ,5,6,Å. The materials feature high thermal stability and permanent porosity with relatively small pore diameters which are attributed to the extensive strong dative bonding between the metal centers and formate molecules. The title compounds exhibit interesting multi-fold gas adsorption and magnetic properties. The adsorption study of a series of alcohols, aromatics, and linear hydrocarbons revealed strong control of the adsorbent channel structures on their adsorption capacity and selectivity. The study also indicated possibility of using these materials for separation of close boiling chemicals (e.g., ethylbenzene and p-xylene) via pressure swing adsorption (PSA) process and molecules with different diffusion parameters via kinetic-based process. Three-dimensional spontaneous magnetic ordering was found in all three network structures investigated and at ground states they behave somewhat like soft magnets. [source]

Monte Carlo probabilistic sensitivity analysis for patient level simulation models: efficient estimation of mean and variance using ANOVA

HEALTH ECONOMICS, Issue 10 2007
Anthony O'Hagan
Abstract Probabilistic sensitivity analysis (PSA) is required to account for uncertainty in cost-effectiveness calculations arising from health economic models. The simplest way to perform PSA in practice is by Monte Carlo methods, which involves running the model many times using randomly sampled values of the model inputs. However, this can be impractical when the economic model takes appreciable amounts of time to run. This situation arises, in particular, for patient-level simulation models (also known as micro-simulation or individual-level simulation models), where a single run of the model simulates the health care of many thousands of individual patients. The large number of patients required in each run to achieve accurate estimation of cost-effectiveness means that only a relatively small number of runs is possible. For this reason, it is often said that PSA is not practical for patient-level models. We develop a way to reduce the computational burden of Monte Carlo PSA for patient-level models, based on the algebra of analysis of variance. Methods are presented to estimate the mean and variance of the model output, with formulae for determining optimal sample sizes. The methods are simple to apply and will typically reduce the computational demand very substantially. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Benzo[a]heptalenes from Heptaleno[1,2- c]furans.

HELVETICA CHIMICA ACTA, Issue 4 2007

Abstract It is shown in this ,Part 2' that heptaleno[1,2- c]furans 1 react thermally in a Diels,Alder -type [4+2] cycloaddition at the furan ring with vinylene carbonate (VC), phenylsulfonylallene (PSA), , -(acetyloxy)acrylonitrile (AAN), and (1Z)-1,2-bis(phenylsulfonyl)ethene (ZSE) to yield the corresponding 1,4-epoxybenzo[d]heptalenes (cf. Schemes,1, 5, 6, and 8). The thermal reaction of 1a and 1b with VC at 130° and 150°, respectively, leads mainly to the 2,3- endo -cyclocarbonates 2,3- endo - 2a and - 2b and in minor amounts to the 2,3- exo -cyclocarbonates 2,3- exo - 2a and - 2b. In some cases, the (P*)- and (M*)-configured epimers were isolated and characterized (Scheme,1). Base-catalyzed cleavage of 2,3- endo - 2 gave the corresponding 2,3-diols 3, which were further transformed via reductive cleavage of their dimesylates 4 into the benzo[a]heptalenes 5a and 5b, respectively (Scheme,2). In another reaction sequence, the 2,3-diols 3 were converted into their cyclic carbonothioates 6, which on treatment with (EtO)3P gave the deoxygenated 1,4-dihydro-1,4-epoxybenzo[d]heptalenes 7. These were rearranged by acid catalysis into the benzo[a]heptalen-4-ols 8a and 8b, respectively (Scheme,2). Cyclocarbonate 2,3- endo - 2b reacted with lithium diisopropylamide (LDA) at ,70° under regioselective ring opening to the 3-hydroxy-substituted benzo[d]heptalen-2-yl carbamate 2,3- endo - 9b (Scheme,3). The latter was O -methylated to 2,3- endo -(P*)- 10b. The further way, to get finally the benzo[a]heptalene 13b with MeO groups in 1,2,3-position, could not be realized due to the fact that we found no way to cleave the carbamate group of 2,3- endo -(P*)- 10b without touching its 1,4-epoxy bridge (Scheme,3). The reaction of 1a with PSA in toluene at 120° was successful, in a way that we found regioisomeric as well as epimeric cycloadducts (Scheme,5). Unfortunately, the attempts to rearrange the products under strong-base catalysis as it had been shown successfully with other furan,PSA adducts were unsuccessful (Scheme,4). The thermal cycloaddition reaction of 1a and 1b with AAN yielded again regioisomeric and epimeric adducts, which could easily be transformed into the corresponding 2- and 3-oxo products (Scheme,6). Only the latter ones could be rearranged with Ac2O/H2SO4 into the corresponding benzo[a]heptalene-3,4-diol diacetates 20a and 20b, respectively, or with trimethylsilyl trifluoromethanesulfonate (TfOSiMe3/Et3N), followed by treatment with NH4Cl/H2O, into the corresponding benzo[a]heptalen-3,4-diols 21a and 21b (Scheme,7). The thermal cycloaddition reaction of 1 with ZSE in toluene gave the cycloadducts 2,3- exo - 22a and - 22b as well as 2- exo,3- endo - 22c in high yields (Scheme,8). All three adducts eliminated, by treatment with base, benzenesulfinic acid and yielded the corresponding 3-(phenylsulfonyl)-1,4-epoxybenzo[d]heptalenes 25. The latter turned out to be excellent Michael acceptors for H2O2 in basic media (Scheme,9). The Michael adducts lost H2O on treatment with Ac2O in pyridine and gave the 3-(phenylsulfonyl)benzo[d]heptalen-2-ones 28a and 3- exo - 28b, respectively. Rearrangement of these compounds in the presence of Ac2O/AcONa lead to the formation of the corresponding 3-(phenylsulfonyl)benzo[a]heptalene-1,2-diol diacetates 30a and 30b, which on treatment with MeONa/MeI gave the corresponding MeO-substituted compounds 31a and 31b. The reductive elimination of the PhSO2 group led finally to the 1,2-dimethoxybenzo[a]heptalenes 32a and 32b. Deprotonation experiments of 32a with t -BuLi/N,N,N,,N,-tetramethylethane-1,2-diamine (tmeda) and quenching with D2O showed that the most acid CH bond is HC(3) (Scheme,9). Some of the new structures were established by X-ray crystal-diffraction analyses (cf. Figs.,1, 3, 4, and 5). Moreover, nine of the new benzo[a]heptalenes were resolved on an anal. Chiralcel OD-H column, and their CD spectra were measured (cf. Figs.,8 and 9). As a result, the 1,2-dimethoxybenzo[a]heptalenes 32a and 32b showed unexpectedly new Cotton -effect bands just below 300,nm, which were assigned to chiral exciton coupling between the heptalene and benzo part of the structurally highly twisted compounds. The PhSO2 -substituted benzo[a]heptalenes 30b and 31b showed, in addition, a further pair of Cotton -effect bands in the range of 275,245,nm, due to chiral exciton coupling of the benzo[a]heptalene chromophore and the phenylsulfonyl chromophore (cf. Fig.,10). [source]

A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies

HISTOPATHOLOGY, Issue 6 2006
J Melia
Aims:, The frequency of prostatic core biopsies to detect cancer has been increasing with more widespread prostate specific antigen (PSA) testing. Gleason score has important implications for patient management but morphological reproducibility data for British practice are limited. Using literature-based criteria nine uropathologists took part in a reproducibility study. Methods:, Each of the nine participants submitted slides from consecutive cases of biopsy-diagnosed cancer assigned to the Gleason score groups 2,4, 5,6, 7 and 8,10 in the original report. A random selection of slides was taken within each group and examined by all pathologists, who were blind to the original score. Over six circulations, new slides were mixed with previously read slides, resulting in a total of 47 of 81 slides being read more than once. Results:, For the first readings of the 81 slides, the agreement with the consensus score was 78% and overall interobserver agreement was , 0.54 for Gleason score groups 2,4, 5,6, 7, 8,10. Kappa values for each category were 0.33, 0.56, 0.44 and 0.68, respectively. For the 47 slides read more than once, intra-observer agreement was 77%, , 0.66. The study identified problems in core biopsy interpretation of Gleason score at levels 2,4 and 7. Patterns illustrated by Gleason as 2 tended to be categorized as 3 because of the variable acinar size and unassessable lesional margin. In slides with consensus Gleason score 7, 13% of readings were scored 6 and in slides with consensus 6, 18% of readings were scored 7. Conclusions:, Recommendations include the need to increase objectivity of the Gleason criteria but limits of descriptive morphology may have to be accepted. [source]

Influence of Self-Affirmation on Responses to Gain- Versus Loss-Framed Antismoking Messages

HUMAN COMMUNICATION RESEARCH, Issue 4 2010
Xiaoquan Zhao
Self-affirmation has been shown to reduce biased processing of threatening health messages. In this study, the impact of self-affirmation on college smokers' reactions to gain- versus loss-framed antismoking public service announcements (PSAs) was examined. A consistent pattern of interaction was observed wherein self-affirmation produced more favorable responses to loss-framed PSAs and more unfavorable responses to gain-framed PSAs. Self-affirmation also reduced smoking intention in the loss frame condition and increased antismoking self-efficacy across framing conditions. These findings are discussed in light of previous research linking self-affirmation to increased message scrutiny. L'influence de l'affirmation de soi sur les réactions aux messages anti-tabac cadrés autour du gain ou de la perte Xiaoquan Zhao & Xiaoli Nan Il a été démontré que l'affirmation de soi réduit le traitement biaisé des messages menaçants concernant la santé. Dans cette étude, l'impact de l'affirmation de soi sur les réactions des étudiants universitaires fumeurs face à des messages d'intérêt public anti-tabac cadrés autour du gain ou de la perte a été examiné. Une tendance régulière d'interaction a été observée, selon laquelle l'affirmation de soi produisait des réactions plus favorables aux messages cadrés autour de la perte et des réactions plus défavorables aux messages cadrés autour du gain. L'affirmation de soi a également réduit l'intention de fumer dans les conditions de cadrage autour de la perte et a augmenté l'efficacité anti-tabac dans toutes les conditions de cadrage. Ces résultats sont commentés à la lumière de la recherche antérieure observant un lien entre l'affirmation de soi et une augmentation de l'examen attentif des messages. Der Einfluss von Selbstbestätigung auf die Reaktionen zu gewinn- vs. verlustgerahmten Anti-Raucher-Botschaften Xiaoquan Zhao & Xiaoli Nan Bislang konnte gezeigt werden, dass Selbstbestätigung eine voreingenommene Verarbeitung von bedrohlichen Gesundheitsbotschaften vermindert. In dieser Studie untersuchten wir den Einfluss von Selbstbestätigung auf die Reaktionen auf gewinn- vs. verlustgerahmte Anti-Raucher-Public Service Botschaften an einer Population von Universitätsstudierenden. Es zeigte sich ein konsistentes Interaktionsmuster in der Form, dass Selbstbestätigung zu stärker befürwortenden Reaktionen auf verlustgerahmte Botschaften führte und zu stärker ablehnenden Reaktionen auf gewinngerahmte Botschaften. Selbstbestätigung verminderte die Rauchintention in der verlustgerahmten Kondition und erhöhte die Anti-Rauchen-Selbstwirksamkeit für beide Frames. Diese Ergebnisse werden mit Blick auf bestehende Forschung zu Selbstbestätigung und erhöhter Botschaftswahrnehmung diskutiert. La Influencia de la Auto-Afirmación en las Respuestas a los Encuadres de Ganancia Versus de Pérdida de los Mensajes Anti-Tabaco Xiaoquan Zhao & Xiaoli Nan Department of Communication, George Mason University Resumen Se ha demostrado que la auto-afirmación reduce el procesamiento tendencioso de los mensajes de salud amenazantes. En este estudio, el impacto de la auto-afirmación en las reacciones de los estudiantes universitarios fumadores a los encuadres de ganancia- versus de pérdida de los anuncios de servicios públicos (PSA) anti-tabaco AQ1 fueron examinados. Una pauta consistente de interacción fue observada donde la auto-afirmación produjo respuestas más favorables a los PSA de encuadres de pérdida y respuestas más desfavorables a los encuadres de ganancia de los PSA. La auto-afirmación redujo también la intención de fumar en la condición de encuadre de pérdida e incrementó la auto-eficacia anti-tabaco a través de las condiciones de encuadre. Los hallazgos son discutidos a la luz de la investigación previa conectando a la auto-afirmación con el incremento del escrutinio del mensaje. [source]

Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial

INTERNATIONAL JOURNAL OF CANCER, Issue 7 2010
Teemu J. Murtola
Abstract Decreased risk of advanced prostate cancer has been reported among men using statins. However, the evidence on overall prostate cancer risk is conflicting. We compared the relative risk between current users and non-users of statins or other cholesterol-lowering medications in a population undergoing systematical prostate cancer screening. The study cohort comprised of 23,320 men participating in the screening arm of the Finnish prostate cancer screening trial during 1996,2004. Information on medication use was obtained from a comprehensive national prescription database. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HRs) for prostate cancer. Serum prostate-specific antigen (PSA) level was compared between current users and non-users of cholesterol-lowering drugs. Compared with medication non-users, the overall prostate cancer incidence was decreased among statin users [HR 0.75, 95% confidence interval (CI) 0.63,0.89]. The inverse association was dose-dependent with cumulative amount of statin use, and strongest for low-grade and early stage tumors. The incidence was nonsignificantly lower also among users of other types of cholesterol-lowering drugs (HR 0.62, 95% CI 0.28,1.38), but without dose-dependence. Age-adjusted median serum PSA tended to be lower among users of cholesterol-lowering drugs, but the relative risk decrease among statin users was not related to decreased PSA. Overall incidence of prostate cancer was lowered among statin users when bias due to differential PSA testing between medication users and non-users was eliminated by systematical prostate cancer screening. Cholesterol-lowering with statins seems beneficial for prostate cancer prevention. [source]

Evaluation of molecular forms of prostate-specific antigen and human kallikrein 2 in predicting biochemical failure after radical prostatectomy

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2009
Sven Wenske
Abstract Most pretreatment risk-assessment models to predict biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer rely on total prostate-specific antigen (PSA), clinical stage, and biopsy Gleason grade. We investigated whether free PSA (fPSA) and human glandular kallikrein-2 (hK2) would enhance the predictive accuracy of this standard model. Preoperative serum samples and complete clinical data were available for 1,356 patients who underwent RP for localized prostate cancer from 1993 to 2005. A case-control design was used, and conditional logistic regression models were used to evaluate the association between preoperative predictors and BCR after RP. We constructed multivariable models with fPSA and hK2 as additional preoperative predictors to the base model. Predictive accuracy was assessed with the area under the ROC curve (AUC). There were 146 BCR cases; the median follow up for patients without BCR was 3.2 years. Overall, 436 controls were matched to 146 BCR cases. The AUC of the base model was 0.786 in the entire cohort; adding fPSA and hK2 to this model enhanced the AUC to 0.798 (p = 0.053), an effect largely driven by fPSA. In the subgroup of men with total PSA ,10 ng/ml (48% of cases), adding fPSA and hK2 enhanced the AUC of the base model to a similar degree (from 0.720 to 0.726, p = 0.2). fPSA is routinely measured during prostate cancer detection. We suggest that the role of fPSA in aiding preoperative prediction should be investigated in further cohorts. © 2008 Wiley-Liss, Inc. [source]

RM2 antigen (,1,4-GalNAc-disialyl-Lc4) as a new marker for prostate cancer

INTERNATIONAL JOURNAL OF CANCER, Issue 1 2005
Seiichi Saito
Abstract Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, ,1,4-GalNAc-disialyl-Lc4, defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and ,4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern ,4, high Gleason score (,8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer. © 2005 Wiley-Liss, Inc. [source]

Association of kallikrein expression in nipple aspirate fluid with breast cancer risk

INTERNATIONAL JOURNAL OF CANCER, Issue 4 2004
Edward R. Sauter
Abstract Human kallikreins (hK) 2, 3, 6 and 10 are expressed in breast and prostate tissue. hK2 and hK3 (prostate-specific antigen, PSA) are used to screen for prostate cancer. hK6 and hK10 are downregulated in breast cancer compared to normal breast tissue. We demonstrated that levels of PSA in nipple aspirate fluid (NAF) are lower in women with breast cancer than in normal women. We hypothesize that the expression of hK2, 3, 6 and 10 are related and important in detecting breast cancer. The goals of this study are to determine the level of expression of kallikreins in NAF and serum, the association of hK2, 3, 6 and 10 in NAF, and the association of each of the kallikreins with breast cancer. In NAF from 275 women, hK3, 6 and 10 were detectable in , 90% and hK2 in 74% of samples analyzed. NAF levels were highest for hK6 and lowest for hK2, regardless of cancer and menopausal status. hK3 was detectable in 15/29 (52%) and hK2 in 0/29 serum samples collected from 6 women. hK2 and hK3 were concentrated in NAF vs. matched serum. The 4 kallikreins were associated with the exception of hK2 with hK6 or hK10. PSA levels were higher in normal pre- than postmenopausal subjects (but not women with breast cancer), whereas levels of hK2, 6 and 10 did not differ by menopausal status. hK2 and PSA were associated with both pre- and postmenopausal breast cancer; hK6 and 10 were not. hK2 and PSA were more associated with pre- than postmenopausal breast cancer. Using logistic regression, PSA and menopausal status provided the best model of breast cancer prediction, with a sensitivity of 91% and specificity of 39%. In conclusion, 4 kallikreins are expressed in NAF. hK2 and PSA, and hK6 and hK10 are highly associated. Higher premenopausal PSA levels suggest the influence of ovarian steroids. PSA shows the most promise in aiding in the early detection of breast cancer. © 2003 Wiley-Liss, Inc. [source]

The Pacific,South American modes and their downstream effects

INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 10 2001
Kingtse C. Mo
Abstract There are two pervasive modes of atmospheric variability in the Southern Hemisphere (SH) that influence circulation and rainfall anomalies over South America. They appear as leading empirical orthogonal functions (EOFs) of 500-hPa height or 200-hPa streamfunction anomalies and are found from intraseasonal to decadal time scales. Both patterns exhibit wave 3 hemispheric patterns in mid to high latitudes, and a well-defined wave train with large amplitude in the Pacific,South American (PSA) sector. Therefore, they are referred to as the PSA modes (PSA1 and PSA2). PSA1 is related to sea surface temperature anomalies (SSTAs) over the central and eastern Pacific at decadal scales, and it is the response to El Niño,Southern Oscillation (ENSO) in the interannual band. The associated rainfall summer pattern shows rainfall deficits over northeastern Brazil and enhanced rainfall over southeastern South America similar to rainfall anomalies during ENSO. PSA2 is associated with the quasi-biennial component of ENSO, with a period of 22,28 months and the strongest connections occur during the austral spring. The associated rainfall pattern shows a dipole pattern with anomalies out of phase between the South Atlantic Convergence Zone (SACZ) extending from central South America into the Atlantic and the subtropical plains centred at 35°S. These two modes are also apparent in tropical intraseasonal oscillations for both summer and winter. Eastward propagation of enhanced convection from the Indian Ocean through the western Pacific to the central Pacific is accompanied by a wave train that appears to originate in the convective regions. The positive PSA1 pattern is associated with enhanced convection over the Pacific from 150°E to the date line. The convection pattern associated with PSA2 is in quadrature with that of PSA1. Both PSA modes are influenced by the Madden Julian Oscillation and influence rainfall over South America. Copyright © 2001 Royal Meteorological Society [source]

Updated Japanese Urological Association Guidelines on prostate-specific antigen-based screening for prostate cancer in 2010

INTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2010
The Committee for Establishment of the Guidelines on Screening for Prostate Cancer
Abstract The exposure rate of screening for prostate cancer using prostate-specific antigen (PSA) in Japan is still very low compared with that in the USA or western Europe. The mortality rate of prostate cancer will increase in the future and in 2020 it will be 2.8-fold higher than in 2000. Therefore, there is an urgent need to determine the best available countermeasures to decrease the rate of prostate cancer death. PSA screening, which can reduce the risk of death as a result of prostate cancer, should be offered to all men at risk of developing prostate cancer with fact sheets showing updated benefits and drawbacks of screening for prostate cancer. [source]

Safety and efficacy of docetaxel, estramustine phosphate and hydrocortisone in hormone-refractory prostate cancer patients

INTERNATIONAL JOURNAL OF UROLOGY, Issue 7 2010
Yoshihiro Nakagami
Objective: To assess the combination of docetaxel (DTX), estramustine phosphate (EMP) and hydrocortisone for patients with hormone-refractory prostate cancer (HRPC). Methods: A total of 63 patients with HRPC were treated with a chemotherapeutic regimen including DTX, EMP, and hydrocortisone. Clinical and pathological features were correlated to serum prostate-specific antigen (PSA) recurrence and survival rates. Incidence and degree of toxicities were also retrospectively reviewed. Results: A median of 11 courses of chemotherapy was administered per patient. PSA levels decreased by >50% in 32 (51%) patients and >90% in 18 (29%) patients. Median time to PSA progression was 6 months (range from 1 to 41 months) and median time of overall survival was 14 months (range from 1 to 56 months). In a univariate analysis to predict overall survival, PSA, hemoglobin, alkaliphosphatase, and performance status prior to the chemotherapy were significant factors. Despite grade 3,4 neutropenia in 87% of patients, grade 5 interstitial pneumonia in one patient and grade 4,5 myocardial infarction in two patients were recognized, the regimen seemed to be relatively safe. Conclusions: Combination chemotherapy with DTX, EMP and hydrocortisone provides survival benefits for patients with HRPC with an acceptable toxicity profile. We need to further evaluate who might benefit most from this regimen. [source]

Development and internal validation of a nomogram predicting extracapsular extension in radical prostatectomy specimens

INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2010
Naoya Satake
Objectives: To present a nomogram predicting the side-specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens. Methods: Three hundred and fifty-four patients with T1c-T3a prostate cancer undergoing RP were included in the analysis. A receiver operating characteristic (ROC) analysis was carried out to evaluate the predictive values of each clinical and pathological factor, separately and in combination. Based on logistic regression analysis, a nomogram predicting the side-specific probability of ECE was developed. Results: Overall, 146 (40%) of 354 patients and 165 (23%) of 708 lobes had ECE pathologically. The areas under the ROC curve (AUC) of the standard features, such as serum PSA, clinical stage and biopsy Gleason sum on each side, in predicting side-specific probability of ECE were 0.624, 0.627, and 0.747, respectively. When these three features were combined, AUC increased to 0.773 which was not significantly different from 0.791 of maximum percent of cancer alone (P = 0.613) and significantly enhanced by including maximum percent of cancer on each side, 0.799 (P = 0.022). The resulting nomogram was internally validated and had excellent calibration. Conclusions: The accuracy in predicting ECE is increased by combining standard clinical factors (clinical stage, serum PSA, highest Gleason score) and biopsy features, such as maximum percent of cancer in the cores. The developed nomogram is helpful when deciding whether or not neurovascular bundles can be preserved. [source]

Update on prostate-specific antigen (PSA)-based screening

INTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2009
Hiroyoshi Suzuki md Deputy Editor
No abstract is available for this article. [source]

Prostate specific antigen (PSA)-based screening

INTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2008
Hiroyoshi Suzuki md Deputy Editor
First page of article [source]

Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer

INTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2008
Koshiro Nishimoto
Objectives: To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer. Methods: One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease. Results: Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer (P < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters. Conclusions: The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy. [source]

Review Article: Economic evaluation of prostate cancer screening with prostate-specific antigen

INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2008
Tomoaki Imamura
Abstract: Economic issues cannot be ignored in conducting prostate cancer screening using prostate-specific antigen (PSA). Through an electronic search, we reviewed five descriptive cost studies and nine cost-effectiveness/cost-utility analyses concerning PSA screening. Most of the existing evidence was based on mathematical model analysis and the results are enormously disparate. The cost per quality-adjusted life years (QALY) gained was estimated to be $US 63.37 to $68.32, and $8400 to $23 100, respectively, or was dominated by no screening. Economic studies evaluating PSA screening are still far from sufficient. Urologists, epidemiologists and health economists must jointly conduct further studies on not only mortality but also quality of life assessment and economic evaluation, using randomized clinical trials, for a strict evaluation of the actual efficacy of PSA screening. At present, patients should be thoroughly informed of the limitations of PSA screening and, in consultation with urological specialists, make the personal decision of whether to receive it. [source]

Value of power Doppler sonography with 3D reconstruction in preoperative diagnostics of extraprostatic tumor extension in clinically localized prostate cancer

INTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2008
Miroslav Zalesky
Aim: The aim of the study is to investigate the value of preoperative power Doppler sonography with 3D reconstruction (3D-PDS) for diagnostics of extraprostatic extension of prostate cancer. Patients and Methods: In the prospective study we examined 146 patients with clinically localized prostate cancer who underwent radical prostatectomy. Prior to surgery, each patient underwent 3D-PDS, transrectal ultrasound (TRUS), and digital rectal examination (DRE). Furthermore, we determined the prostate volume, prostate specific antigen (PSA) level, PSA density (PSAD), and Gleason score. The risk of locally advanced cancer was assessed using Partin tables. We determined the sensitivity, specificity, and predictive values of these diagnostic procedures. We plotted the receiver operating characteristic (ROC) curves and calculated the areas under the curves (AUC). Multivariate logistic regression was used to identify the significant predictors of extraprostatic tumor extension. Based on this we developed diagnostic nomograms maximizing the probability of accurate diagnosis. Results: The significant differences between patients with organ confined and locally advanced tumor (based on the postoperative assessment) were observed in the PSA levels (P < 0.014), PSAD (P < 0.004), DRE (P < 0.037), TRUS (P < 0.003), and 3D-PDS (P < 0.000). The highest AUC value of 0.776 (P < 0.000) was found for 3D-PDS. The observed AUC value for TRUS was 0.670 (P < 0.000) and for PSAD 0.639 (P < 0.004). In multivariate regression analysis, the PSAD, preoperative Gleason score, and 3D-PDS finding were identified as significant preoperative predictors of extraprostatic tumor extension. Conclusion: Our data suggest that the 3D-PDS is a valuable preoperative diagnostic examination to identify locally advanced prostate cancer. Therefore, it can be used to maximize the probability of the accurate diagnosis of extraprostatic tumor extension. [source]

Impact of salvage therapy for biochemical recurrence on health-related quality of life following radical prostatectomy

INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2007
Shunichi Namiki
Objective: To determine the impact of salvage therapy for prostate-specific antigen (PSA) recurrence on the health-related quality of life (HRQOL) of patients after radical retropubic prostatectomy (RP). Methods: Between January 2000 and December 2003, a total of 249 patients who underwent RP were available for 2-year follow up. Of the respondents, 203 men did not show evidence of recurrence (group A), and 46 men received salvage hormonal therapy and/or radiotherapy after RP because of a rise in PSA (group B). The general and prostate-target HRQOL was assessed with the Medical Outcomes Study 36-Item Short Form and University of California, Los Angeles Prostate Cancer Index, respectively. Patients completed the HRQOL instruments by mail at baseline and at 24 months after RP. Results: All of the patients completed both questionnaires. At baseline no significant differences were found between the two groups in any of the HRQOL domains. There were significant improvements in mental health and social function for the patients without biochemical recurrence postoperatively. Repeated measure anova revealed significantly different patterns of alteration in several general HRQOL domains among the treatment groups. The urinary and bowel domains were equivalent between the two treatment groups at baseline and 24 months after RP. The patients treated with salvage hormonal therapy tended to show delayed recovery of sexual function. Conclusion: Using a self-administered questionnaire, biochemical recurrence following RP was found to impose a substantial burden in patients with localized prostate cancer. [source]