bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aurora‐A over‐expression in high‐grade PIN lesions and prostate cancer
Authors: McKlveen Buschhorn Holly , Klein Robert R. , Chambers Susan M. , Hardy Margaret C. , Green Sylvan , Bearss David , Nagle Raymond B. 
Published: March 2005

AbstractBACKGROUNDOver‐expression of Aurora‐A (Aurora 2 kinase, STK‐15), a protein found in centrosomes thought to be associated with genetic instability, has been previously documented in prostate cancer [Pihan et al.: Cancer Res 61(5):2212–2219, 2001]. It is unknown if this protein is also over‐expressed in high‐grade prostatic intraepithelial neoplasia (PIN) lesions.METHODSPIN lesions were examined for increased Aurora‐A using immunohistochemical staining on archival paraffin embedded prostatectomy tissue. Aurora‐A expression was scored using size, number, and staining intensity. Protein expression was examined and compared between stromal cells, normal glands, high‐grade PIN lesions, and invasive cancer.RESULTSImmunohistochemistry shows an increased expression of Aurora‐A in 96% of high‐grade PIN cases, and 98% in cancer lesions. Twenty‐nine percent of cases of normal glands from cancerous prostates also showed increased Aurora‐A expression.CONCLUSIONSOver‐expression of Aurora‐A is present in some normal and the majority of high‐grade PIN lesions indicating that this may be an early event that leads to the genetic instability seen in prostate carcinogenesis. © 2005 Wiley‐Liss, Inc.
Population‐based risk assessment for other cancers in relatives of hereditary prostate cancer (HPC) cases
Authors: Albright Lisa A. Cannon , Schwab Angela , Camp Nicola J. , Farnham James S. , Thomas Alun 
Published: March 2005

AbstractBACKGROUNDTo identify associations of other cancers with hereditary prostate cancer (HPC) we estimated relative risks (RRs) of 36 different cancers in relatives of prostate cancer cases in the Utah Population Data Base (UPDB), which combines genealogical and cancer data for Utah.METHODSWe utilized known genetic relationships between prostate cancer cases and their relatives with cancer, combined with age‐ and sex‐specific cancer rates calculated internally from the UPDB, to estimate RRs for cancer in relatives of prostate cancer cases.RESULTSMultiple other cancers were observed in excess in both first‐ and second‐degree relatives of HPC cases including colon cancer, non‐Hodgkins lymphoma, multiple myeloma, rectal cancer, cancer of the gallbladder, and melanoma (skin).CONCLUSIONSThis analysis supports the existence of heritable prostate cancer syndromes that include other cancers. We hypothesize that the study of homogeneous pedigrees co‐segregating prostate cancer and another cancer could allow more straightforward localization and identification of the gene(s) responsible. © 2005 Wiley‐Liss, Inc.
Genome‐wide screen for prostate cancer susceptibility genes in men with clinically significant disease
Authors: Chang Bao‐Li , Isaacs Sarah D. , Wiley Kathy E. , Gillanders Elizabeth M. , Zheng S. Lilly , Meyers Deborah A. , Walsh Patrick C. , Trent Jeffrey M. , Xu Jianfeng , Isaacs William B. 
Published: March 2005

AbstractBACKGROUNDOne of the difficulties confronting genetic studies of prostate cancer is the complex and heterogeneous etiology. Given the high population frequency of lesions meeting the histological definition of prostate cancer, a significant portion of men with a positive family history may be diagnosed due to increased surveillance and associated higher likelihood of biopsy. Over diagnosis decreases power to detect genes that increase susceptibility to a clinically significant prostate cancer.METHODSWe re‐evaluated all 623 men with prostate cancer in our 188 hereditary prostate cancer families and identified a subset of 244 men with more aggressive disease based upon meeting at least one of the following clinical and/or pathologic criteria: tumor grade Gleason score ≥7, tumor stage T2c or higher, pretreatment PSA ≥20 ng/ml, rising PSA after treatment, evidence of metastasis, or death from prostate cancer.RESULTSGenome‐wide screens were re‐performed by defining men as affected only if they met the criteria for clinically significant disease. The new analyses identified stronger evidence for linkage in Xq27‐28 and 22q, as well as several novel loci, including 3p and 9p.CONCLUSIONSAlthough, these results need to be confirmed in independent studies, our approach represents an important step to overcome the impact of over diagnosis in genetic studies of prostate cancer. Larger studies that incorporate this approach are needed. © 2005 Wiley‐Liss, Inc.
Obtaining fresh prostate cancer tissue for research: A novel biopsy needle and sampling technique for radical prostatectomy specimens
Authors: Walton Thomas J. , McCulloch Thomas A. , Rees Robert C. , Bishop Michael C. 
Published: March 2005

AbstractBACKGROUNDFresh or fresh‐frozen tissue samples are preferred for molecular profiling as formalin fixation degrades intracellular nucleic acids. Radical prostatectomy (RP) specimens are a valuable source of prostate cancer tissue, but the reliance on whole‐organ pathological processing for prognostication limits sampling opportunities. Few studies have addressed specific harvesting techniques using prostatectomy specimens.MATERIALS AND METHODSEx vivo biopsies were performed on 23 consecutive fresh RP specimens using a purpose‐designed needle. A standard sextant approach was used with an additional lateral biopsy on each side. Cores from each lobe were snap‐frozen together and sections assessed by a pathologist blinded to the RP and pre‐operative biopsy pathology. Comparison with pre‐operative biopsies was performed using the t‐test and χ2 statistical tests. Eleven randomly selected RP specimens were further evaluated for the effects of needle tracks and margin perforation.RESULTSCancer was detected in 19 of 23 specimens, giving a sensitivity of 83.6%. The average tumor involvement was 28.3% per section compared with 15.6% for pre‐operative biopsies (P < 0.02). There was no statistically significant difference between the groups for either Gleason sum score concordance or tumor location concordance. In 3 of 11 cases, needle margin perforation was identified; in none of the cases did it compromise pathological assessment, although in one case a deeper block resection was required.CONCLUSIONSEx vivo biopsy is a useful technique for retrieving fresh tissue whilst preserving organ morphology in RP specimens. The purpose‐designed needle and harvesting technique provide good yields of cancer tissue from a high proportion of sampled prostatectomy specimens. © 2005 Wiley‐Liss, Inc.
Experimental direct evaluation of functional barriers in PET recycled bottles: comparison of migration behaviour of mono‐ and multilayers
Authors: Pennarun P. Y. , Saillard P. , Feigenbaum A. , Dole P. 
Published: March 2005

AbstractRecycling of used bottles into new bottles is associated with possible migration of pollutants arising from the previous life of the packages. To reduce or delay such migration, the recycled resin is depolluted or a functional barrier layer made of virgin plastics is used. Testing migration from such recycled bottles relies on the use of model pollutants (surrogates). In order to enable modelling of migration kinetics, each step of the use of surrogates is carefully investigated here in the case of PET. First, criteria underlying the selection of surrogates are carefully examined; together with volatility, polarity and diffusion behaviour, it is shown here that their solubility in the food simulant and their chemical stability strongly influence migration results. For aqueous test media, 2,4‐pentanedione and phenol should be used as surrogates. Second, a procedure is developed to impregnate surrogates at very large concentrations (several thousands of mg/kg PET) which are necessary to monitor migration kinetics. This procedure, which uses dichloromethane as solvent, allows a quick and reproducible impregnation, not sensitive to temperatures between 11–23°C, factors which favour its use at a plant scale. Third, flakes impregnated with this procedure are processed into bottles, and their physicochemical properties are compared to those of commercial bottles. Last, monolayer and tri‐layer polluted bottles (model pollutants in inner layer) are tested for migration for more than 1.5 years. With multilayers, the migration lag time of the fastest surrogates is 6 months with 3% acetic acid and 3 months with ethanol as the simulant, due to plasticization of PET by ethanol. The sequence of migration of surrogates is different with monolayer and multilayer bottles, which shows that partition effects (solubility) play an essential role, especially with monolayer materials. Copyright © 2005 John Wiley & Sons, Ltd.
Theoretical study of laser light generation and color image formation:FA1:Cs+andFA2:Li+centers at the low coordination (100) and (110) surfaces of AgCl and AgBr
Authors: Shalabi A. S. , Kamel M. A. , Ammar H. Y. 
Published: March 2005

AbstractTheFA1:Cs+andFA2:Li+color centers at the low coordination (100) and (110) surfaces of AgCl and AgBr play important roles in laser light generation and color image formation. Double‐well potentials at these surfaces are investigated by using ab initio calculations. Quantum clusters were embedded in the simulated Coulomb fields that closely approximate the Madelung fields of the host surfaces, and ions that are the nearest neighbors to theFA− defect site are allowed to relax to equilibrium. The calculated Stokes shifts suggest that laser light generation is sensitive to the simultaneous effects of the vibrational coupling mode, the impurity cation, the coordination number of the surface ion, the lattice anion, and the choice of the basis set centered on the anion vacancy. An attempt has been made to explain these effects in terms of Madelung potential, electron affinity, and optical–optical conversion efficiency. All relaxed excited states of the defect‐containing surfaces are deep below the lower edges of the conduction bands of the ground‐state defect‐free surfaces, suggesting that theFA(I):Cs+andFA(II):Li+centers are suitable laser defects. The dependence of orientational destruction, recording sensitivity, and exciton (energy) transfer on the empty cation; the coordination number of the surface ion; and the lattice anion is clarified. The Glasner–Tompkins empirical rule was generalized to include the impurity cation and the coordination number of the surface ion. As far as color image formation is concerned, the supersensitizer was found to increase the sensitizing capabilities of two primary dyes in the excited states by increasing the relative yield of quantum efficiency. The (110) surfaces of AgBr and AgCl were more sensitive than the corresponding (100) surfaces, and AgBr thin film was found to be more sensitive than that of AgCl. On the basis of quasi‐Fermi levels, the difference in the sensitizing capabilities between the examined dyes in the excited states is determined. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
An AES study of Sn surface segregation in Cu single crystals
Authors: Asante J. K. O. , Terblans J. J. , Roos W. D. 
Published: March 2005

AbstractQuantitative treatment of Sn segregation data in the three low‐index planes of Cu(111), Cu(110) and Cu(100) was carried out. Auger electron spectroscopy (AES) was used to acquire the data by heating the sample linearly with time (positive linear temperature ramp, PLTR) from 450 to 900 K and immediately cooling it linearly with time (negative linear temperature ramp, NLTR) from 900 to 650 K. The experimental data were fitted using the Darken model for the PLTR profiles. Two supportive models—Fick's integral and the Bragg–Williams equations—were used to extract the starting segregation parameters for the Darken model. Fick's integral was used to fit part of the data for the PLTR profile and the Bragg–Williams equations were used for the NLTR profile, which accounts for an extended equilibrium segregation region.The Sn segregation parameters, namely the interaction energy ΩCuSn, the diffusion coefficient D and the segregation energy ΔG, were found as:

Copyright © 2005 John Wiley & Sons, Ltd.
The Use of Dielectric Permittivity for the Control of the Biomass Level during Biotransformations of Toxic Substrates in Continuous Culture
Authors: Markx Gerard H. , Kell Douglas B. 
Published: March 2005

AbstractSince the permittivity signal of a cell suspension measured using dielectric spectroscopy at radio frequencies is essentially determined only by viable (intact) cells, it can be used to monitor the concentration of viable cells in a fermentor in which a large proportion of the cells is nonviable. This could be used to select for organisms that are highly resistant to stress, for example from toxic chemicals used in biotransformations. We sought to control the concentration of viable yeast cells in a fermentor by adding small amounts of benzaldehyde, thus imposing a selection regime for cells highly resistant to benzaldehyde. However, after the addition of benzaldehyde, an increase in the permittivity is seen first followed by a decrease, thus making the control of biomass using a standard on‐off controller difficult. It is shown that it is possible effectively to control the level of viable biomass in the fermentor in the presence of a large concentration of necromass using a combination of an inverse response compensator and a PID controller.
Muscarinic receptor binding, plasma concentration and inhibition of salivation after oral administration of a novel antimuscarinic agent, solifenacin succinate in mice
Authors: Oki Tomomi , Sato Shuichi , Miyata Keiji , Yamada Shizuo 
Published: March 2005

A novel muscarinic receptor antagonist, solifenacin succinate, inhibited specific binding of [N‐methyl‐3H]‐scopolamine ([3H]‐NMS) in the mouse bladder, submaxillary gland and heart in a concentration‐dependent manner. This inhibitory effect was greatest in the submaxillary gland, followed by the bladder and heart.
After oral administration of oxybutynin (76.1 μmol kg−1) or solifenacin (62.4, 208 μmol kg−1), a significant dose‐ and time‐dependent increase in KD values for specific [3H]‐NMS binding was seen in the bladder, prostate, submaxillary gland, heart, colon and lung, compared with control values. The increase in KD induced by oxybutynin in each tissue reached a maximum 0.5 h after oral administration and then rapidly declined, while that induced by solifenacin was greatest 2 h after administration and was maintained for at least 6 or 12 h, depending on the dose. The muscarinic receptor binding of oral solifenacin was slower in onset and of a longer duration than that of oxybutynin.
Plasma concentrations of oxybutynin and its active metabolite (N‐desethyl‐oxybutynin, DEOB) were maximum 0.5 h after its oral administration and then declined rapidly. Oral solifenacin persisted in the blood for longer than oxybutynin.
Pilocarpine‐induced salivary secretion in mice was significantly reduced by oral administration of solifenacin and was completely abolished 0.5 h after oral oxybutynin. Although the suppression induced by solifenacin was more persistent than that due to oxybutynin, the antagonistic effect of solifenacin on the dose–response curves to pilocarpine was significantly weaker than that of oxybutynin. It is concluded that oral solifenacin persistently binds to muscarinic receptors in tissues expressing the M3 subtype, such as the bladder.

British Journal of Pharmacology (2005) 145, 219–227. doi:10.1038/sj.bjp.0706184
Lessons from the English smoking treatment services
Authors: Raw Martin , McNeill Ann , Coleman Tim 
Published: March 2005

ABSTRACTThis paper summarizes and discusses the key findings of the evaluation of the English  smoking  treatment  services,  which  were  established  in  1999  as part of the English National Health Service. Within 4 years these services existed throughout the country and were working at full capacity, a total of £76 million having been spent on them over this period, excluding medication costs. In the fourth year almost 235 000 people attended treatment and set a quit date, and the total budget, including medications, was approximately £50 million. At the end of the fourth year the government allocated £138 million for the services for the period April 2003–March 2006. The CO‐validated 4‐week abstinence rate was 53%, the validated 52‐week abstinence rate was 15%, and the relapse rate from 4 to 52 weeks was 75%. There was no sex difference in cessation rates at long‐term follow‐up. The cessation results and relapse rate from weeks 4 to 52 are consistent with results from published studies, including clinical trials. The estimated cost per life‐year saved was £684 and the figure is even lower if the potential future health care cost savings are taken into account at £438 per life‐year saved. This compares with the benchmark of £20 000 per life‐year saved, which the National Institute for Clinical Excellence (NICE) is using to recommend new health care interventions in the National Health Service. The services were also succeeding in reaching disadvantaged smokers. However, there have been problems, and other health care systems considering an initiative of this kind should: set national training standards and increase training capacity before launching the services; standardize the provision of pharmaceutical treatments and make them as accessible as possible before launching the services; and give the services at least 5 years of central funding to allow them to become well established. Monitoring is extremely important but should not be so much of a burden that it detracts from developing a quality service and although cessation targets can be helpful, care needs to be taken that they are reasonable and do not promote throughput at the expense of quality.
Paracetamol: a haemorrhagic risk factor in patients on warfarin
Authors: Mahé I. , Bertrand N. , Drouet L. , Simoneau G. , Mazoyer E. , Bal dit Sollier C. , Caulin C. , Bergmann J. F. 
Published: March 2005

AimTo quantify the effect of paracetamol on the anticoagulant effect of warfarin under normal clinical conditions.Patients and methodsIn a prospective double‐blind, cross‐over, placebo‐controlled study, 11 patients on stable warfarin therapy received in random order two 14‐day regimens of paracetamol 4 g day−1 or placebo, with a 14‐day or more wash‐out period in between, time necessary to fulfil the inclusion criteria.ResultsIn patients on paracetamol, the mean maximum increase in the International Normalized Ratio (INR) observed was 1.04 ± 0.55 vs. 0.20 ± 0.32 in those on placebo (P = 0.003). The mean maximum INR observed was significantly higher with paracetamol than with placebo (3.47 vs. 2.61, P = 0.01). In patients receiving paracetamol, the mean observed INR was significantly increased after 4 days (+ 0.6 ± 0.6, P < 0.001).ConclusionParacetamol at 4 g day−1 induces a significant increase in INR in patients receiving a stable regimen of warfarin, increasing the risk of bleeding associated with warfarin.
Effects of clarithromycin on lansoprazole pharmacokinetics betweenCYP2C19genotypes
Authors: Saito Masato , Yasui‐Furukori Norio , Uno Tsukasa , Takahata Takenori , Sugawara Kazunobu , Munakata Akihiro , Tateishi Tomonori 
Published: March 2005

AimsLansoprazole is a substrate of CYP2C19 and CYP3A. The aim of this study was to compare the inhibitory effects of clarithromycin, an inhibitor of CYP3A on the metabolism of lansoprazole betweenCYP2C19genotypes.MethodsA two‐way randomized double‐blind, placebo‐controlled crossover study was performed. Eighteen volunteers, of whom six were homozygous extensive metabolizers (EMs), six were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, received two 6‐day courses of either clarithromycin 800 mg or placebo daily in a randomized fashion with a single oral dose of lansoprazole 60 mg on day 6 in all cases. Plasma concentrations of lansoprazole and its metabolites, 5‐hydroxylansoprazole and lansoprazole sulphone were monitored up to 24 h after dosing.ResultsDuring placebo administration, the mean AUC(0, ∞) of lansoprazole in homozygous EMs, heterozygous EMs and PMs were 4652 (95% CI, 2294, 7009) ng ml−1 h, 8299 (4784, 11814) ng ml−1 h and 25293 (17643, 32943) ng ml−1 h (P < 0.001), respectively. Clarithromycin treatment significantly increasedCmaxby 1.47‐fold, 1.71‐fold and 1.52‐fold and AUC(0, ∞) of lansoprazole by 1.55‐fold, 1.74‐fold, and 1.80‐fold in these genotype groups, respectively, whereas elimination half‐life was prolonged only in PMs. The clarithromycin‐mediated percent increase in pharmacokinetic parameters such asCmax, AUC(0, ∞) or elimination half‐life did not differ between the threeCYP2C19genotypes.ConclusionsThe present study indicates that there are significant drug interactions between lansoprazole and clarithromycin in allCYP2C19genotype groups probably through CYP3A inhibition. The bioavailability of lansoprazole might, to some extent, be increased through inhibition of P‐glycoprotein during clarithromycin treatment.
Relationship between the C3435T and G2677T(A) polymorphisms in the ABCB1 gene and P‐glycoprotein expression in human liver
Authors: Owen Andrew , Goldring Chris , Morgan Paul , Chadwick David , Park B. Kevin , Pirmohamed Munir 
Published: March 2005

AimsThe aim of the study was to determine whether a correlation exists between MDR1 (ABCB1) gene polymorphisms at positions 3435 (C3435T) and 2677 (G2677T(A)) and the expression of human hepatic P‐glycoprotein (P‐gp).MethodsP‐gp protein expression in 26 human livers was assessed by Western blotting and ABCB1 mRNA expression was determined by real time RT‐PCR. The C3435T and G2677T(A) polymorphisms were identified by RFLP and direct sequence analysis, respectively.ResultsThe C and G allele frequencies for the C3435T and G2677T(A) polymorphisms were 0.48 and 0.79, respectively, and the genotypes were in Hardy–Weinberg equilibrium. There was a 200‐ and 20‐fold variation in the expression of ABCB1 mRNA and Pgp protein expression, respectively. There were no differences in mRNA and protein expression identified amongst the different genotypes attributable to the C3435T and G2677T(A) polymorphisms in the ABCB1 gene. Exposure to a PXR ligand prior to death did not influence mRNA or protein expression.ConclusionsThere is substantial variability in the expression of Pgp in human liver, but this is not due to the presence of C3435T and G2677T(A) polymorphisms in the ABCB1 gene, although our study is limited by a small sample size.