bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of metabolic activation and DNA adduct formation by the human carcinogen diethylstilbestrol: The defining link to natural estrogens
Authors: Saeed Muhammad , Rogan Eleanor , Cavalieri Ercole 
Published: October 2008

AbstractDiethylstilbestrol (DES) is a human carcinogen, based on sufficient epidemiological evidence. DES is mainly metabolized to its catechol, 3′‐hydroxyDES (3′‐OH‐DES), which can further oxidize to DES‐3′,4′‐quinone (DES‐3′,4′‐Q). Similarly to estradiol‐3,4‐quinone, the reaction of DES‐3′,4′‐Q with DNA would form the depurinating 3′‐OH‐DES‐6′‐N3Ade and 3′‐OH‐DES‐6′‐N7Gua adducts. To prove this hypothesis, synthesis of DES‐3′,4′‐Q by oxidation of 3′‐OH‐DES with Ag2O was tried; this failed due to instantaneous formation of a spiro‐quinone. Oxidation of 3′‐OH‐DES by lactoperoxidase or tyrosinase in the presence of DNA led to the formation of 3′‐OH‐DES‐6′‐N3Ade and 3′‐OH‐DES‐6′‐N7Gua adducts. These adducts were tentatively identified by LC‐MS/MS as 3′‐OH‐DES‐6′‐N3Ade, m/z = 418 [M+H]+, and 3′‐OH‐DES‐6′‐N7Gua, m/z = 434 [M+H]+. Demonstration of their structures derived from their oxidation by MnO2 to the DES quinone adducts and subsequent tautomerization to the dienestrol (DIES) catechol adducts, which are identical to the standard 3′‐OH‐DIES‐6′‐N3Ade, m/z = 416 [M+H]+, and 3′‐OH‐DIES‐6′‐N7Gua, m/z = 432 [M+H]+, adducts. The reaction of DIES‐3′,4′‐Q or lactoperoxidase‐activated 3′‐OH‐DIES with DNA did not produce any depurinating adducts, due to the dienic chain being perpendicular to the phenyl planes, which impedes the intercalation of DIES into the DNA. Enzymic oxidation of 3′‐OH‐DES suggests that the catechol of DES intercalates into DNA and is then oxidized to its quinone to yield N3Ade and N7Gua adducts. These results suggest that the common denominator of tumor initiation by the synthetic estrogen DES and the natural estrogen estradiol is formation of their catechol quinones, which react with DNA to afford the depurinating N3Ade and N7Gua adducts. © 2008 Wiley‐Liss, Inc.
An intron 4 VNTR polymorphism of the endothelial nitric oxide synthase gene is associated with early‐onset colorectal cancer
Authors: Yeh Chih‐Ching , Santella Regina M. , Hsieh Ling‐Ling , Sung Fung‐Chang , Tang Reiping 
Published: October 2008

AbstractEndothelial‐derived nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), may play an important role in colorectal carcinogenesis. However, the putative contribution of commoneNOSgenetic polymorphisms to colorectal cancer risk remains unknown. We genotyped 3 polymorphisms ofeNOS(T‐786C, G894T, and intron4b/a) in 727 colorectal adenocarcinoma cases and 736 age‐ and sex‐matched healthy controls in Taiwan. Genotypes of the T‐786C and G894T polymorphisms were determined by fluorescence polarization assays and the 27‐bp variable number of tandem repeat (VNTR) polymorphism in intron 4 (intron4b/a) was analyzed by PCR. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among younger participants (≤60 yrs), the intron4a variant genotype was associated with a significantly increased risk of colorectal cancer, compared with the intron4bb genotype (OR = 1.60, 95% CI = 1.04–2.46). In addition, those young individuals bearing a greater number of high‐risk genotypes (OR > 1,i.e., CT+TT for T‐786C, ba+aa for intron4b/a, and GG for G894T) ofeNOShad a higher colorectal cancer risk (ptrend= 0.039). Compared with younger individuals without any putative high‐risk genotypes, those with 3 high‐risk genotypes had a significantly greater cancer risk (OR = 1.89, 95% CI = 1.04–3.43). Our results suggest that theeNOSintron4b/a polymorphism may contribute to early‐onset colorectal cancer risk in the Taiwanese population. © 2008 Wiley‐Liss, Inc.
HAI‐2 is epigenetically downregulated in human hepatocellular carcinoma, and its Kunitz domain type 1 is critical for anti‐invasive functions
Authors: Tung Edmund Kwok‐Kwan , Wong Chun‐Ming , Yau Tai‐On , Lee Joyce Man‐Fong , Ching Yick‐Pang , Ng Irene Oi‐Lin 
Published: October 2008

AbstractPharmacological demethylation‐based gene expression profile analysis is a useful tool to identify epigenetically silenced tumour suppressor genes. HGF activator inhibitor 2 (HAI‐2), a serine protease inhibitor, has been identified as one of the candidate tumour suppressor genes in human hepatocellular carcinoma (HCC) with this technique. In this study, we aimed to characterise the epigenetic status and tumour suppressive function of HAI‐2 in HCC. We validated that HAI‐2 expression was either absent or low in most of the HCC cell lines tested, and 5‐Aza‐2′‐deoxycytidine treatment significantly restored its expression in 9 (75%) of these 12 cell lines. HAI‐2 was found to be frequently underexpressed in human HCCs (p < 0.001). With bisulphite DNA sequencing and methylation‐specific PCR, we found that the promoter of the HAI‐2 gene was frequently hypermethylated in both HCC cell lines and human HCCs. Ectopic expression of HAI‐2 significantly inhibited cell migration and invasiveness of HCC cells in vitro and suppressed tumourigenicity in vivo. In addition, we also provided the first evidence that HAI‐2 mediated its tumour suppressor function via the Kunitz domain 1 (KD‐1), as KD‐1 but not KD‐2 inactivating mutant abolished its anti‐tumour invasiveness in vitro. Our findings suggest that HAI‐2 is a candidate tumour suppressor gene that is frequently hypermethylated and underexpressed in human HCCs, and the KD‐1 domain of HAI‐2 is the key region responsible for its anti‐invasive function. © 2008 Wiley‐Liss, Inc.
Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: A meta‐analysis
Authors: De Vuyst Hugo , Clifford Gary M. , Nascimento Maria Claudia , Madeleine Margaret M. , Franceschi Silvia 
Published: October 2008

AbstractThis meta‐analysis investigated human papillomavirus (HPV) prevalence in vulvar, vaginal and anal intraepithelial neoplasia (VIN, VAIN, AIN) grades 1–3 and carcinoma from 93 studies conducted in 4 continents and using PCR assays. Overall HPV prevalence was 67.8%, 85.3% and 40.4% among 90 VIN1, 1,061 VIN2/3 and 1,873 vulvar carcinomas; 100%, 90.1% and 69.9% among 107 VAIN1, 191 VAIN2/3 and 136 vaginal carcinomas; and 91.5%, 93.9% and 84.3% among 671 AIN1, 609 AIN2/3 and 955 anal carcinomas, respectively. HPV16 was found more frequently (>75%) and HPV18 less frequently (<10%) in HPV‐positive vulvar, vaginal and anal carcinomas than in cervical carcinoma. HPV6 and 11 were common in VIN1 and AIN1, but not in VAIN1. HPV prevalence in vulvar carcinoma varied most by histological type (69.4% in warty‐basaloid and 13.2% in keratinized type) and was also higher in women 60 years or younger and in studies carried out in North America. HPV prevalence in anal carcinoma was higher among women (90.8%) than men (74.9%), but no difference by gender emerged in North America. The majority of AIN2/3 derived from studies of HIV‐positive individuals and/or men who have sex with men. Among AIN2/3, HIV infection was associated with higher HPV prevalence, more multiple‐type infections and a relative under‐representation of HPV16. In conclusion, ∼40% of vulvar, 60% of vaginal and 80% of anal carcinoma may be avoided by prophylactic vaccines against HPV16/18. This proportion would be similar for the corresponding high‐grade lesions of the vagina and anus, but higher for VIN2/3 (75%) than for vulvar carcinoma. © 2008 Wiley‐Liss, Inc.
Diminished IFN‐γ and IL‐10 and elevated Foxp3 mRNA expression in the cervix are associated with CIN 2 or 3
Authors: Scott Mark E. , Ma Yifei , Kuzmich Lili , Moscicki Anna‐Barbara 
Published: October 2008

AbstractCervical mucosal expression of cytokines involved in mediating cellular immunity is believed to influence the persistence of human papillomavirus (HPV) infection, a necessary prerequisite for the development of cervical intraepithelial neoplasia (CIN). Additionally, regulatory T (Treg) cells are increasingly understood to be important modulators of cellular immunity. Using quantitative RT‐PCR, we measured, in cross‐sectional design, the cervical mRNA expression of IFN‐γ, IL‐10, and IL‐12, as well as the Treg transcription factor Forkhead box P3 (Foxp3), in a cohort of young women representing CIN 1, 2, and 3, as well as benign histology. Higher levels of IFN‐γ and IL‐10 were significantly (p ≤ 0.05) associated with decreased odds of having high‐grade cervical disease (CIN 2 or 3) in multivariate logistic regression models. In contrast, higher levels of mucosal Foxp3 expression were associated with increased odds of having CIN 2 or 3 (p = 0.004). In a multivariate model including cervical infection with HPV16 and/or another high‐risk HPV type, Foxp3 remained higher in the CIN 2/3 group, but the difference was notably less significant (p = 0.05). These findings support a model in which diminished cellular immunity in the cervical mucosa and mucosal enrichment of Treg cells both contribute to the development of high‐grade lesions. © 2008 Wiley‐Liss, Inc.
Downregulation of vascular endothelial growth factor and induction of tumor dormancy by 15‐lipoxygenase‐2 in prostate cancer
Authors: Tang Yong , Wang Man‐Tzu , Chen Yakun , Yang Dianer , Che Mingxin , Honn Kenneth V. , Akers Gregory D. , Johnson Stephen R. , Nie Daotai 
Published: October 2008

AbstractThe enzyme 15‐lipoxygenase‐2 (15‐LOX‐2) utilizes arachidonic acid, a polyunsaturated fatty acid, to synthesize 15(S)‐hydroxyeicosatetraenoic acid. Abundantly expressed in normal prostate epithelium but frequently suppressed in the cancerous tissues, 15‐LOX‐2 has been suggested as a functional suppressor of prostate cancer, but the mechanism(s) involved remains unknown. To study the functional role of 15‐LOX‐2 in prostate cancer, we expressed 15‐LOX‐2 as a fusion protein with GFP in DU145 and PC‐3 cells and found that 15‐LOX‐2 increased cell cycle arrest at G0/G1 phase. When injected into athymic nu/nu mice, prostate cancer cells with 15‐LOX‐2 expression could still form palpable tumors without significant changes in tumorigenicity. But, the tumors with 15‐LOX‐2 expression grew significantly slower than those derived from vector controls and were kept dormant for a long period of time. Histological evaluation revealed an increase in cell death in tumors derived from prostate cancer cells with 15‐LOX‐2 expression, while in vitro cell culture conditions, no such increase in apoptosis was observed. Further studies found that the expression of vascular endothelial growth factor A (VEGF‐A) was significantly reduced in prostate cancer cells with 15‐LOX‐2 expression restored. Our studies suggest that 15‐LOX‐2 suppresses VEGF gene expression and sustains tumor dormancy in prostate cancer. Loss of 15‐LOX‐2 functionalities, therefore, represents a key step for prostate cancer cells to exit from dormancy and embark on malignant progression in vivo. © 2008 Wiley‐Liss, Inc.
Optical knock out of stem cells with extremely ultrashort femtosecond laser pulses
Authors: Uchugonova Aisada , Isemann Andreas , Gorjup Erwin , Tempea Gabriel , Bückle Rainer , Watanabe Wataru , König Karsten 
Published: October 2008

AbstractNovel ultracompact multiphoton sub‐20 femtosecond near infrared 85 MHz laser scanning microscopes and conventional 250 fs laser microscopes have been used to perform high spatial resolution two‐photon imaging of stem cell clusters as well as selective intracellular nanoprocessing and knock out of living single stem cells within an 3D microenvironment without any collateral damage. Also lethal cell exposure of large parts of cell clusters was successfully probed while maintaining single cells of interest alive. The mean power could be kept in the milliwatt range for 3D nanoprocessing and even in the microwatt range for two‐photon imaging. Ultracompact low power sub‐20 fs laser systems may become interesting tools for optical nanobiotechnology such as optical cleaning of stem cell clusters as well as optical transfection. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The titanium binding protein of Rhodococcus ruber GIN1 (NCIMB 40340) is a cell‐surface homolog of the cytosolic enzyme dihydrolipoamide dehydrogenase
Authors: Siegmann Ari , Komarska Avital , Betzalel Yifaat , Brudo Irene , Jindou Sadanari , Mor Gil , Fleminger Gideon 
Published: October 2008

AbstractRhodococcus ruber GIN1 (formally Rh. strain GIN1) was previously isolated on the basis of its strong adherence to coal fly ash (CFA) and titanium dioxide particles from CFA sedimentation ponds of an electrical power plant in Israel. The interaction of the bacterium with oxides has been shown to be mediated by a cell surface protein designated TiBP (titanium binding protein) involving primarily strong, non‐electrostatic forces. In this work, we set forward to identify this unique exocellular protein. Sequence analysis of the purified protein by mass spectrometry (LC/MS/MS) following trypsinization revealed 11 peptides. All of them showed >90% amino acid residues identity with sequences of one of the orthologs (dldh1) of the cytosolic enzyme dihydrolipoamide dehydrogenase (DLDH), based on the genome sequence of Rhodococcus strain RHA1. This genome was selected as a reference since currently it is the only sequenced Rhodococcal genome. Altogether, these peptides covered over 25% of the 52 kDa protein molecule. N‐ and C‐termini primers were prepared and used to sequence the paralog gene from Rh. ruber GIN1 after polymerase chain reaction (PCR) amplification. All 11 peptides showed 100% identity with the sequence of this gene. The homology of TiBP with the supposedly cytosolic DLDH raised the question of whether the exocellular TiBP possesses DLDH activity. Indeed, intact late logarithmic phase Rh. ruber GIN1 cells, previously shown to express TiBP, were found to possess such activity, while very low activity was associated with stationary phase cells which possess diminished TiBP expression on their surface. Further evidence for the exocellular location of TiBP/DLDH was achieved using specific anti‐TiBP polyclonal antibodies by whole cell and protein enzyme‐linked immunosorbent assay (ELISA), showing high reactivity of the logarithmic phase cell surface and substantially lower reactivity with the stationary phase cells. As expected, logarithmic phase spheroplasts were not recognized by these antibodies. Similar results were obtained by fluorescence and scanning electron microscopy. Our postulation that DLDH is located on the surface of Rh. ruber GIN1, serving as a TiO2 binding protein, is in accordance with literary evidence on DLDH in other organisms, Bacteria, Archea, and Eukaryots that suggests it is associated with the outer membranes or cell surfaces. As an exocellular protein DLDH assumes various tasks which are not related to its classical role as a 2‐oxoacid dehydrogenase, including serving as an adhesion/binding protein in certain bacteria. Copyright © 2008 John Wiley & Sons, Ltd.
Understanding SERS of bacteria
Authors: Efrima S. , Zeiri L. 
Published: October 2008

AbstractSurface‐enhanced Raman spectroscopy (SERS) has been suggested as a powerful tool to identify bacteria, drawing from its high fingerprint (vibrational) information content, its extreme sensitivity (down to the single molecule level) and its obliviousness to the aqueous environment intrinsic to biological systems. We review here in a comparative manner the various studies that attempted to utilize SERS for this important goal in light of the work carried out by our own group over the past 10 years or so. We show that SERS has an additional major advantage, namely, it introduces a new dimension of selectivity, which, on the one hand, makes it even more suitable as an analytical tool, but on the other hand, it requires gaining control of the precise manner in which the SERS‐active metal centers are produced and brought into contact with the micro‐organism. Our emphasis in this review is on understanding the spectra in terms of the nature of the SERS‐active centers and their placement within the bacterium. On the interpretation and assignment of the spectra, we constantly keep in mind the final goal of bacteria identification. Copyright © 2008 John Wiley & Sons, Ltd.
Simultaneous enantioseparation of four β2‐agonists by capillary electrophoresis with cyclodextrin additives. Study of the enantioselective mechanism
Authors: Yang Jing , Lu Xiumei , Pan Li , Jiang Kun , Cheng Maosheng , Li Famei 
Published: October 2008

AbstractThe simultaneous capillary electrophoretic enantioseparation of adrenergic β2‐agonists enantiomers (trantinterol, mabuterol, clenbuterol, bambuterol) was studied with β‐cyclodextrin, ethyl‐β‐CD, methyl‐β‐CD, hydroxypropyl‐β‐CD, and hydroxyethyl‐β‐CD as chiral selector. The type and concentration of the chiral selector and buffer pH played a very important role in the enantioseparation of the analyzed compounds. Hydroxypropyl‐β‐CD was found to be the most effective complexing agent and allowed excellent chiral/achiral resolutions compared to the other CDs. The simultaneous enantioseparation of four β2‐agonists was achieved using 100 mM citric acid–10 mM Na2HPO4 buffer at pH 2.5 containing 120 mM hydroxypropyl‐β‐CD with an applied voltage of 20 kV. Method validation in terms of repeatability, linearity, and limits of detection and quantification was performed. The effect of structural features of analytes on Rs and tm was studied. Complexation binding constants for the interactions between the four compounds and three different CDs were evaluated for elucidating the enantioseparation mechanism. It was found that very small differences in the chemical structure of the analytes resulted in significant changes in stereoselective recognition.
Determination of pharmaceuticals in drinking water by CD‐modified MEKC: Separation optimization using experimental design
Authors: Drover Vincent J. , Bottaro Christina S. 
Published: October 2008

AbstractA suite of 12 widely used pharmaceuticals (ibuprofen, diclofenac, naproxen, bezafibrate, gemfibrozil, ofloxacin, norfloxacin, carbamazepine, primidone, sulphamethazine, sulphadimethoxine and sulphamethoxazole) commonly found in environmental waters were separated by highly sulphated CD‐modified MEKC (CD‐MEKC) with UV detection. An experimental design method, face‐centred composite design, was employed to minimize run time without sacrificing resolution. Using an optimized BGE composed of 10 mM ammonium hydrogen phosphate, pH 11.5, 69 mM SDS, 6 mg/mL sulphated β‐CD and 8.5% v/v isopropanol, a separation voltage of 30 kV and a 48.5 cm×50 μm id bare silica capillary at 30°C allowed baseline separation of the 12 analytes in a total analysis time of 6.7 min. Instrument LODs in the low milligram per litre range were obtained, and when combined with offline preconcentration by SPE, LODs were between 4 and 30 μg/L.
Dielectric cell separation of fine needle aspirates from tumor xenografts
Authors: Cristofanilli Massimo , Krishnamurthy Savitri , Das Chandra M. , Reuben James M. , Spohn William , Noshari Jamileh , Becker Frederick , Gascoyne Peter R. 
Published: October 2008

AbstractAs an approach to isolating tumor cells from fine needle biopsy specimens, we investigated a dielectric cell preparation method using an in vivo xenographic tumor model. Cultured human MDA‐MB‐435 tumor cells were grown as solid tumors in nude mice and fine needle aspiration biopsies were conducted. Biopsied cells were suspended in sucrose medium and collected on slides patterned with microelectrode arrays (electrosmears) energized by electrical signals in the range 10 to 960 kHz. The unlabeled cells adhered to characteristic regions of the slides in accordance with their morphology as a result of dielectric forces. Tumor cells were trapped between 40 and 60 kHz and were separated according to whether they were mitotic, large and complex, or small. Damaged tumor cells were captured at between 60 and 120 kHz; granulocytes between 70 and 90 kHz; lymphocytes between 85 and 105 kHz; healthy erythrocytes between 140 and 180 kHz, and damaged erythrocytes above 180 kHz. Using intrinsic cell characteristics, the electrosmear presented cell subpopulations from fine needle aspiration biopsy specimens in a manner that is compatible with automated slide‐based analysis systems. The approach has the potential to facilitate the analysis of the role of cell subpopulations in disease.
Comparison of performance of Chirobiotic T, T2 and TAG columns in the separation of β2‐ and β3‐homoamino acids
Authors: Pataj Zoltán , Ilisz István , Berkecz Robert , Misicka Aleksandra , Tymecka Dagmara , Fülöp Ferenc , Armstrong Daniel W. , Péter Antal 
Published: October 2008

AbstractThe enantiomers of eight unusual β2‐ and β3‐homoamino acids were separated on chiral stationary phases containing the macrocyclic glycopeptide antibiotic teicoplanin (Chirobiotic T or T2) or teicoplanin aglycone (Chirobiotic TAG) as chiral selectors. The effects of the organic modifier, the mobile phase composition, and temperature on the separations were investigated. Linear van't Hoff plots were observed in the studied temperature range, 280–318 K, and the changes in enthalpy, Δ(ΔH°), entropy, Δ(ΔS°), and free energy, Δ(ΔG°) were calculated. The values of the thermodynamic parameters depended on the nature of the selectors, the structures of the analytes, and especially the positions of the substituents on the analytes. A comparison of the separation performances of the macrocyclic glycopeptide stationary phases revealed that the Chirobiotic TAG column exhibited much better selectivity for β2‐homoamino acids, while the separation of β3‐homoamino acid enantiomers was better on Chirobiotic T or T2. The elution sequence was determined in some cases and was observed to be R < S.
Modeling GC‐ECD retention times of pentafluorobenzyl derivatives of phenol by using artificial neural networks
Authors: Asadpour‐Zeynali Karim , Jalili‐Jahani Naser 
Published: October 2008

AbstractThe depicted retention times (RTs) of an electron capture detection (ECD) system is predicted for a set of 37 pentafluorobenzyl (PFB) derivatives of phenol in a semi‐polar column, DB‐1701 (14% cyanopropylphenyl and 86% dimethyl‐polysiloxane). Among a large number of descriptors, four parameters categorized as electronic, topological, geometric, and hybrid (geometric and topological) descriptors are chosen using stepwise multiple regression technique. Each molecular descriptor in this model was disputed to unfold the relationship between molecular structures and their RTs. The descriptors occurring in the multiple linear regression (MLR) model were considered as inputs for developing the back propagation artificial neural networks (BPANN). The artificial neural network (ANN) model shows superiority over the MLR by decerning 91.9% for different classes of molecules in confusion matrix. This refers to the fact that the retention behaviors of molecules display nonlinear characteristics. The accuracy of 4‐4‐1 BPANN model was illustrated using leave‐one‐out (LOO), leave‐multiple‐out (LMO) cross‐validations, and Y‐randomization. Moreover, the mean effect of descriptors betrays that descriptor Ss is the most indispensable factor affecting the retention behavior of molecules.
Statistical and methodological issues in the analysis of complex sample survey data: Practical guidance for trauma researchers
Authors: West Brady T. 
Published: October 2008

AbstractStandard methods for the analysis of survey data assume that the data arise from a simple random sample of the target population. In practice, analysts of survey data sets collected from nationally representative probability samples often pay little attention to important properties of the survey data. Standard statistical software procedures do not allow analysts to take these properties of survey data into account. A failure to use more specialized procedures designed for survey data analysis can impact both simple descriptive statistics and estimation of parameters in multivariate models. In this article, the author provides trauma researchers with a practical introduction to specialized methods that have been developed for the analysis of complex sample survey data.