bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective study of urinary excretion of 7‐methylguanine and the risk of lung cancer: Effect modification by mu class glutathione‐S‐transferases
Authors: Loft Steffen , Svoboda Peter , Kasai Hiroshi , Tjønneland Anne , Møller Peter , Sørensen Mette , Overvad Kim , Autrup Herman , Raaschou‐Nielsen Ole 
Published: June 2007

AbstractNitrosamines are mainly mutagenic through methylation of DNA. 7‐Methylguanine (m7Gua) is a product of base excision repair and spontaneous depurination of such lesions in DNA and a metabolite from RNA. Associations between urinary excretion of m7Gua and risk of lung cancer were examined in a population‐based cohort of 25,717 men and 27,972 women aged 50–64 years. During 3–7 years follow‐up 260 cases with lung cancer were identified and a subcohort of 263 individuals matched on sex, age and smoking duration was selected for comparison. Urine collected at entry was analyzed for m7Gua by HPLC. Effect modification by glutathione‐S‐transferases GSTM1, GSTM3, GSTT1 and GSTP1 was investigated. We found higher excretion of m7Gua among current smokers than among former smokers. The IRR (incidence rate ratio) of lung cancer was 1.20 (95% CI: 1.00–1.43) per doubling of m7Gua excretion in unadjusted analysis and 1.12 (95% CI: 0.93–1.35) after adjustment for smoking status, intensity and duration at entry. This association was mainly present among current smokers. Comparing the highest with the lowest tertile of m7Gua excretion the IRR of lung cancer was 1.75 (95% CI: 1.04–2.95) irrespective of genotype and 2.75 (95% CI: 1.33–5.81) in subjects with GSTM1 null genotype. If not caused by residual confounding by smoking a possible association between m7Gua excretion and lung cancer supports the importance of methylation of guanine. The finding of an association between m7Gua excretion and lung cancer risk mainly among current smokers and subjects with GSTM1 null genotype supports causality in this respect. © 2007 Wiley‐Liss, Inc.
Abnormal expression of M1/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancer
Authors: Forgue‐Lafitte Marie‐Elisabeth , Fabiani Bettina , Levy Pierre P. , Maurin Nicole , Fléjou Jean‐François , Bara Jacques 
Published: June 2007

AbstractThe abnormal expression of gastric M1/MUC5AC mucin in precancerous lesions and colon cancer evidenced by immunohistochemistry led us to check for its presence in the mucus obtained directly from patients undergoing surgery for cancerous (adenocarcinoma) or inflammatory (diverticulitis or ulcerative colitis) diseases. In parallel, the authors quantified aberrant crypt foci (ACF) and their immunolabelling by M1/MUC5AC in mucosae of cancer and diverticulitis patients. Immuno‐Radio‐Metric Assay of M1/MUC5AC mucin developed by the authors was used to detect M1/MUC5AC mucin in the colonic mucus scraped from surgical specimens. M1/MUC5AC mucin was detected in the mucus of 51/69 (74%) patients with colon adenocarcinoma, versus 7/27 (26%) patients with diverticulitis (threshold: 30 units of M1 mucin per mg protein, area under ROC curve: 0.80). M1/MUC5AC was present in significantly (p < 0.001) larger amounts in the mucus of cancer versus diverticulitis patients. All (10/10) patients with ulcerative colitis tested showed levels above the threshold and their mucosae were strongly labelled with the anti‐M1/MUC5AC antibody by immunohistochemistry. Patients with cancer exhibited 3 fold more ACF than those with diverticulitis, but no significant difference was observed in the mean size and M1/MUC5AC expression pattern of ACF between these two groups. The expression of M1/MUC5AC was in correlation with their size. In macroscopically normal mucosa, ACF were the most important source of M1/MUC5AC mucin. Testing of M1/MUC5AC can enhance the detection of precancerous lesions and colon cancer. © 2007 Wiley‐Liss, Inc.
Camptothecin‐induced apoptosis is enhanced by Myc and involves PKCdelta signaling
Authors: Albihn Ami , Mo Hao , Yang Ying , Henriksson Marie 
Published: June 2007

AbstractThe MYC oncogene is frequently deregulated in human tumors, indicative of a poor prognosis because of enhanced resistance to treatment. In such cases, the cellular sensitivity to chemotherapy could be restored by reactivation of Myc‐driven apoptosis. We have analyzed apoptosis induced by the cytotoxic agents camptothecin (CPT) and paclitaxel (PTX) using Rat1 fibroblasts with different c‐myc status and human Tet21N neuroblastoma cells with conditional MYCN expression. In these cell lines, the drug sensitivity was enhanced by Myc in line with previous reports showing that Myc sensitizes to apoptosis induction by many different apoptosis inducers. CPT‐induced apoptosis involved cleavage and activation of proapoptotic Bid and Bax, induction of mitochondrial membrane depolarization, activation of caspase‐9 and caspase‐3, protein kinase c delta (PKCδ) signaling and upregulation of p53. We also observed reduced transcriptional activity by Myc and other transcription factors in response to CPT. In contrast, the manner by which Myc potentiates the apoptosis induced by PTX differs from that of CPT and remains to be explored. In summary, our findings revealed that activation of PKCδ in response to CPT treatment requires Myc and is important in CPT‐mediated apoptosis signaling. © 2007 Wiley‐Liss, Inc.
Identification of tumorigenic retinal stem‐like cells in human solid retinoblastomas
Authors: Zhong Xiufeng , Li Yongping , Peng Fuhua , Huang Bing , Lin Jianxian , Zhang Wenxin , Zheng Jianliang , Jiang Ruzhang , Song Ge , Ge Jian 
Published: June 2007

AbstractRetinoblastoma (RB) is the most common malignant tumor of the retina in human children. Although it has been hypothesized for a long time that RB derives from multipotent retinal stem cells (RSCs) or retinoblasts, the direct evidence that the presence of tumorigenic RSCs in RB tumors is still lacking. Some studies indicate that malignant tumors contain tumor stem cells similar to their normal tissue stem cell counterparts. With in vitro culture and differentiation method we demonstrate that tumorigenic retinal stem‐like cells (RSLCs) indeed exist in RB lesions and that RB tumor‐derived cultures encompass undifferentiated cells capable of extensive proliferation as clonal nonadherent neurospheres and can differentiate into different retinal cells in vitro. Interestingly, cultured cells expressed retinal development related genes including nestin, CD133, pax6, chx10 and Rx, and overexpressed Bmi‐1, a gene required for self‐renewal and proliferation of stem cells. Significantly, when these cultured cells were intraocularly transplanted into SCID mice, they gave rise to new tumors with histomorphological features and immunophenotypes similar to their parental primary RBs. The results show that RBs contain tumorigenic RSLCs that contribute to tumorigenesis. This study provides a new insight to investigate the histogenesis of RBs and establishes a model for other RB research. © 2007 Wiley‐Liss, Inc.
Increased expression of the inflammatory protein YKL‐40 in precancers of the breast
Authors: Qin Wenyi , Zhu Weizhu , Schlatter Lisa , Miick Ronald , Loy Timothy S. , Atasoy Ulus , Hewett John E. , Sauter Edward R. 
Published: June 2007

AbstractSerum levels of YKL‐40 have been associated with inflammatory diseases and breast cancer. Our purpose was to determine if YKL‐40 in breast tissue, nipple aspirate fluid (NAF) and serum is (i) concentrated in NAF compared to matched serum, (ii) increased in the NAF, serum or tissue of women with biopsy proven precancer or cancer compared to healthy women and (iii) influenced by menopausal status. 118 women (61 healthy subjects, 10 with precancer and 47 with breast cancer) aged 17–95 years provided NAF with or without serum samples for analysis. Matched tissue was analyzed from a subset of subjects who underwent breast biopsy. All NAF and serum samples had detectable levels of YKL‐40. Median YKL‐40 levels for the entire cohort were 683 fold higher in NAF than serum. Premenopausal subjects had higher NAF and lower serum levels of YKL‐40 than postmenopausal subjects. YKL‐40 levels in NAF but not serum were higher in women with precancer (atypical hyperplasia and lobular carcinoma in situ) than in either healthy subjects (p = 0.025) or subjects with breast cancer (p = 0.015). In women with precancer, YKL‐40 distribution in tissue correlated with YKL serum level (p = 0.043). YKL‐40 is concentrated in NAF, with the highest concentrations in premenopausal women. NAF levels of YKL‐40 are significantly higher in women with precancers than healthy subjects, suggesting that measuring YKL‐40 in NAF may improve the identification of women at increased breast cancer risk. © 2007 Wiley‐Liss, Inc.
The traditional Chinese herbal compound rocaglamide preferentially induces apoptosis in leukemia cells by modulation of mitogen‐activated protein kinase activities
Authors: Zhu Jia Y. , Lavrik Inna N. , Mahlknecht Ulrich , Giaisi Marco , Proksch Peter , Krammer Peter H. , Li‐Weber Min 
Published: June 2007

AbstractWith an increasing cancer rate worldwide, there is an urgent quest for the improvement of anticancer drugs. One of the main problems of present chemotherapy in treatment of tumor patients is the toxicity of drugs. Most of the existent anticancer drugs, unfortunately, attack also proliferating normal cells. In recent years, traditional Chinese herbal remedies have gradually gained considerable attention as a new source of anticancer drugs. Although their healing mechanisms are still largely unknown, some of the drugs have been used to help cancer patients fight their disease at reduced side effects compared to other treatments. In our study, we show that Rocaglamide (Roc), derived from the traditional Chinese medicinal plants Aglaia, induces apoptosis through the intrinsic death pathway in various human leukemia cell lines and in acute lymphoblastic leukemia, chronic myeloid leukemia and acute myeloid leukemia cells freshly isolated from patients. Investigation of the molecular mechanisms by which Roc kills tumors revealed that it induces a consistent activation of the stress‐response mitogen‐activated protein kinase (MAPK) p38 accompanied with a long‐term suppression of the survival MAPK extracellular signal‐regulated kinase. These events affect proapoptotic Bcl‐2 family proteins leading to depolarization of the mitochondrial membrane potential and trigger caspase‐mediated apoptosis involving caspase‐9, ‐8, ‐3 and ‐2. Importantly, Roc shows no effects on MAPKs in normal lymphocytes and therefore has no or very low toxicity on healthy cells. Up to now, more than 50 different Roc derivatives have been isolated from Aglaia. Our study suggests that Roc derivatives may be promising candidates for the development of new drugs against hematologic malignancies. © 2007 Wiley‐Liss, Inc.
Capital market integration, currency crises, and exchange rate regimes 1990–2002
Authors: Clark Ephraim , Zenaidi Amel , Trabelsi Monia Gharbi 
Published: June 2007

AbstractThe international capital market integration and currency crises of the last decade have renewed the debate on optimal exchange rate regimes. Research is mixed regarding what their effect has been on the system of exchange rate regimes and the anchor currencies at the centre of the system. The debate is complicated by growing empirical evidence that the de jure regimes announced by governments often differ from the de facto regimes that are actually applied. In this paper we divide the period 1990–2002 according to the major crises and use the generalized method of moments to identify the individual de facto regimes and relevant anchor currencies for each sub‐period. We find that although intermediate regimes as a percentage of the overall database remained stable over the three periods, the type of peg and anchor currencies varied considerably. Pegs on a single currency fell from 62% of the sample in the first period to 49% in the second period, then rose to 66% in the third period. Basket pegs rose from 33% in the first period to 51% in the second period and back to 34% in the third period. Independent floats disappeared after the first period. When we group countries according to their access to capital markets, we find that all nine of the developed countries in the sample followed some type of intermediate regime for all three periods. We also find a trend towards hard pegs in the group of countries that has managed to increase its integration in the international capital markets. Our results also suggest that the US dollar remains the main anchor currency in the international financial system, even after the major currency crises and the rise of the euro. Copyright © 2007 John Wiley & Sons, Ltd.
Scaffold's surface geometry significantly affects human stem cell bone tissue engineering
Authors: Graziano Antonio , d'Aquino Riccardo , Angelis Maria Gabriella Cusella‐De , De Francesco Francesco , Giordano Antonio , Laino Gregorio , Piattelli Adriano , Traini Tonino , De Rosa Alfredo , Papaccio Gianpaolo 
Published: June 2007

AbstractIn this study, we have observed dental pulp stem cells (SBP‐DPSCs) performances on different scaffolds, such as PLGA 85:15, hydroxyapatite chips (HA) and titanium. Stem cells were challenged with each engineered surface, either in plane cultures or in a rotating apparatus, for a month. Gingival fibroblasts were used as controls. Results showed that stem cells exerted a different response, depending on the different type of textured surface: in fact, microconcavities significantly affected SBP‐DPSC differentiation into osteoblasts, both temporally and quantitatively, with respect to the other textured surfaces. Actually, stem cells challenged with concave surfaces differentiated quicker and showed nuclear polarity, an index of secretion, cellular activity and matrix formation. Moreover, bone‐specific proteins were significantly expressed and the obtained bone tissue was of significant thickness. Thus, cells cultured on the concave textured surface had better cell‐scaffold interactions and were induced to secrete factors that, due to their autocrine effects, quickly lead to osteodifferentiation, bone tissue formation, and vascularization. The worst cell performance was obtained using convex surfaces, due to the scarce cell proliferation on to the scaffold and the poor matrix secretion. In conclusion, this study stresses that for a suitable and successful bone tissue reconstruction the surface texture is of paramount importance. J. Cell. Physiol. 214:166–172, 2008. © 2007 Wiley‐Liss, Inc.
Akt2 is implicated in skeletal muscle differentiation and specifically binds Prohibitin2/REA
Authors: Héron‐Milhavet Lisa , Mamaeva Daria , Rochat Anne , Lamb Ned J.C. , Fernandez Anne 
Published: June 2007

AbstractAkt1 and Akt2 are the major isoforms of Akt expressed in muscle cells and muscle tissue. We have performed siRNA silencing of Akt1 and Akt2 in C2 myoblasts to characterize their specific implication in muscle differentiation. Whereas silencing Akt2, and not Akt1, inhibited cell cycle exit and myoblast differentiation, Akt2 overexpression led to an increased proportion of differentiated myoblasts. In addition, we demonstrate that Akt2 is required for myogenic conversion induced by MyoD overexpression in fibroblasts. We show Akt2, but not Akt1, binds Prohibitin2/Repressor of Estrogen Activator, PHB2/REA, a protein recently implicated in transcriptionnal repression of myogenesis. Co‐immunoprecipitation experiments on endogenous proteins showed the Akt2–REA complex does not contain Prohibitin1. We have analyzed expression and localization of PHB2/REA during proliferation and differentiation of mouse and human myoblasts. PHB2/REA shows punctated nuclear staining which partially co‐localizes with Akt2 in differentiated myotubes and PHB2 levels decrease at the onset of myogenic differentiation concomitant with an increase in Akt2. There appears to be an inverse correlation between Akt2 and PHB2 protein levels where cells silenced for Akt2 expression show increased level of PHB2/REA and overexpression of Akt2 resulted in decreased Prohibitin2/REA. Taken together, these results, along with our previous observations, clearly show that Akt2 and not Akt1 plays a major and early role in cell cycle exit and myogenic differentiation and this function involves its specific interaction with PHB2/REA. J. Cell. Physiol. 214:158–165, 2008. © 2007 Wiley‐Liss, Inc.
Placental and spiral artery volume and gray‐scale value assessment via 3‐dimensional sonography in the second trimester
Authors: Zalud Ivica , Shaha Steven 
Published: June 2007

AbstractPurposeExtreme placental size has been associated with abnormal pregnancy outcomes. The purpose of this study was to establish normal values for placental and spiral artery volume and gray‐scale value as assessed via 3‐dimensional (3D) sonography in the second trimester.MethodsThe entry criterion was a documented singleton pregnancy at 14–25 weeks' gestation. Patients with normal pregnancy outcome were stratified into 6 subgroups representing 2‐week intervals. Automatic 3D sonographic acquisition of the placental and spiral artery volume and gray‐scale value, expressed as a percentage, was obtained.ResultsOut of 199 patients with normal pregnancy outcome, the placental volume was between 77.7 and 213.9 cm3 and the gray‐scale value was between 28.6 and 29.2 cm3 (depending on gestational age). The spiral artery volume adjacent to placenta was between 47.9 and 108.7 cm3, and the gray‐scale value was between 27.5 and 29.5 cm3. Statistical analysis in each subgroup of patients revealed a significant difference between placental and spiral artery volumes but no difference when the gray‐scale value was compared.ConclusionsWe defined normal placental and spiralartery volume and gray‐scale value in the secondtrimester of normal pregnancy using 3D sonography. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2007
Color Doppler twinkling artifact in intrauterine fetal demise
Authors: Ozkur Ayhan , Dikensoy Ebru , Kervancioglu Selim , Kervancioglu Resat , İnalöz Serhat , Bayram Metin 
Published: June 2007

AbstractPurposeTo determine whether twinkling artifacts on color and power Doppler sonography could be used as a new sonographic sign of intrauterine fetal demise (IUFD).MethodsIn this prospective study, 24 consecutive pregnant women with IUFD were included after fetal sonographic examinations. Sonographic examination included gray‐scale, color, power, and spectral Doppler imaging. The sonograms were then analyzed for the presence, appearance, and intensity of the twinkling artifacts.ResultsTwinkling artifacts on color Doppler were observed in all of the 24 IUFD as a rapidly changing color Doppler signal complex associated persistently with different parts of the fetal body. The artifacts were localized especially in the neck, back, and iliac regions. Artifact intensity correlated with the time elapsed since death.ConclusionTwinkling artifact was noted in all dead fetuses on color, power, and spectral Doppler examinations. Thus, the observation of these artifacts may be considered as a new sonographic sign of fetal demise, which may reflect the time elapsed since death. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
In vitrointeraction cocktail assay for nine major cytochrome P450 enzymes with 13 probe reactions and a single LC/MSMS run: analytical validation and testing with monoclonal anti‐CYP antibodies
Authors: Tolonen Ari , Petsalo Aleksanteri , Turpeinen Miia , Uusitalo Jouko , Pelkonen Olavi 
Published: June 2007

AbstractA sensitive and rugged LC/MSMS method was developed for a comprehensivein vitrometabolic interaction screening assay with N‐in‐1 approach reported earlier. A cocktail consisting of ten cytochrome P450 (CYP)‐selective probe substrates with known kinetic, metabolic and interaction propertiesin vivowas incubated in a pool of human liver microsomes, and metabolites of melatonin (CYP1A2), coumarin (CYP2A6), bupropion (CYP2B6), amodiaquine (CYP2C8) tolbutamide (CYP2C9), omeprazole (CYP2C19 and CYP3A4), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A4) and testosterone (CYP3A4) were simultaneously analysed with a single LC/MSMS run. Altogether, 13 metabolites and internal standard phenacetin were analysed in multiple reaction mode. Polarity switching mode was utilized to acquire negative ion mode electrospray data for hydroxychlorzoxazone and positive ionization data for the rest of the analytes. Fast gradient elution was applied, giving total injection cycle of 8 min. The method was modified for two different LC/MSMS systems, and was validated for linear range, detection limit, accuracy and precision for each metabolite. In addition, cocktail inhibition system was further tested using monoclonal anti‐CYP antibodies as inhibitors for each probe reaction. Copyright © 2007 John Wiley & Sons, Ltd.
Statistical downscaling of daily precipitation over Greece
Authors: Kioutsioukis Ioannis , Melas Dimitrios , Zanis Prodromos 
Published: June 2007

AbstractThe capability of a multi‐site non‐homogeneous hidden Markov model (NHMM) to downscale winter daily precipitation over Greece is explored for the period 1971–2000. The input variables were selected from NCEP Reanalysis Data following an optimization procedure and include the precipitation rate as predictor. The most parsimonious NHMM identified five weather states. Successively, the forecast skill of the model was tested against sequentially withdrawn data. The NHMM reproduced successfully both thestation‐scale statisticslike the occurrence and amount of precipitation as well as thespatial pattern of precipitationsuch as the correlations between stations and the Log‐Odds ratios. Also, the temporal correlation in the data at most of the rain gauges was successfully captured at seasonal timescales. Finally, the model was capable of reproducing extreme precipitation events. It modelled successfully the dry spells as well as most of the indices corresponding to ‘very wet events’, including the maximum 5‐day precipitation amount, the number of extreme precipitation events and their corresponding fraction of the total precipitation amount, better to the stations where the very wet events are not associated with local scale features that could not be captured by the large‐scale predictors. The weakest reproduced indices correspond to the ‘mean wet day precipitation’ and the ‘90th percentile of precipitation on wet days’ where the model captured their magnitude but not their interannual variability. Copyright © 2007 Royal Meteorological Society
The variation of discharge entering the Niger Delta system, 1951–2000, and estimates of change under global warming
Authors: Itiveh Kingsley O. , Bigg Grant R. 
Published: June 2007

AbstractA simple and effective statistical scheme for estimating river discharges on the River Niger has been derived using catchment rainfall data. Observed station annual average discharges at two locations were correlated with averaged annual rainfall data in recent years (1951–2000). A comparison of the estimated discharge and the observed discharge showed good agreement. The upstream station of Gaya on the border of Niger and Nigeria, with more extensive records, was used to validate the technique. A more limited discharge record at Lokoja, at the focal point of the Niger Delta, is used to reconstruct the discharge over 1951–2000. Despite the extensive dam construction on the Upper Niger during this period the main determinant of flow into the Delta has remained upstream rainfall. The relationship between the past rainfall data and river discharges at Lokoja are used to predict flows in the 2070s using rainfall values derived from various scenarios of a set of coupled climate model simulations. While there is uncertainty even over the sign of future change in west African rainfall, the river flow inferred from those models predicting increased rainfall over the coming century is at a level consistent with rapid change in channel position, as observed during the 1990s. This technique could be applied more widely to forecast future discharges from major river systems. Copyright © 2007 Royal Meteorological Society