bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling treatment‐specific post‐translational modifications in a complex proteome with subtractive substrate phage display
Authors: Tenzer Angela , Hofstetter Barbara , Sauser Christelle , Bodis Stephan , Schubiger August P. , Bonny Christophe , Pruschy Martin 
Published: July 2004

AbstractProteolytic activation of zymogens or controlled degradation of inhibitory factors is part of a major regulatory system on the post‐translational level to regulate treatment induced cellular stress responses. The identification of differential activity based substrates is thus of high interest to prioritize and validate candidate targets for drug discovery. Here we present a novel subtractive substrate phage display screening method for the selection of treatment induced post‐translational peptide modifications in complex proteomes. We investigated this approach with tumor cells in response to a protease activating anticancer treatment modality using subtractive and iterative screening of cellular extracts derived from control and treated cells. Specific phage were identified that served as substrates for proteolytic activities in response to treatment related activity changes and could be distinguished from substrates for unspecific proteolytic background activities. Novel, selected peptide substrates were investigated in vitro and in vivo and showed high substrate specificity and functional biological significance.
Identification of Bacillus anthracis proteins associated with germination and early outgrowth by proteomic profiling of anthrax spores
Authors: Huang Chun‐Ming , Foster K. Wade , DeSilva Tivanka S. , Van Kampen Kent R. , Elmets Craig A. , Tang De‐chu C. 
Published: July 2004

AbstractThe use of anthrax spores as a bioweapon has spurred efforts aimed at identifying key proteins expressed in Bacillus anthracis. Because spore germination and outgrowth occur prior to and are required for disease manifestations, blocking germination and early outgrowth with novel vaccines or inhibitors targeting critical B. anthracis germination and outgrowth‐associated factors is a promising strategy in mitigating bioterror. By screening 587 paired protein spots that were isolated from dormant and germinating anthrax spores, respectively, we identified 10 spore proteins with statistically significant germination‐associated increases and decreases. It is likely that proteins whose levels change during germination may play key roles in the germination and outgrowth processes, and they should be listed as priority targets for development of prophylactic and therapeutic agents against anthrax. The 31 new proteins identified in this study also complement an emerging proteomic database of B. anthracis.
Protein composition of Paracoccus denitrificans cells grown on various electron acceptors and in the presence of azide
Authors: Bouchal Pavel , Přecechtělová Petra , Zdráhal Zbyněk , Kučera Igor 
Published: July 2004

AbstractTwo‐dimensional gel electrophoresis (2‐DE) with immobilized pH gradients was carried out on total cell lysates and membrane fractions of Paracoccus denitrificans with the aim to characterize differences in protein expression during growth under aerobic and various anaerobic conditions (with nitrate, nitrite or nitrous oxide). Comparative image analysis of the protein pattern revealed several subgroups of the total 800 protein spots resolved that were characteristically induced or repressed in response to individual electron acceptors. The respiratory inhibitor azide also exerted a profound influence upon cellular protein composition. However, since most of the proteins showing an altered expression pattern in cells growing on oxygen differed from those in cells growing on nitrite, we suppose that azide acts mainly indirectly, possibly by influencing other cellular signals. Limited information on the P. denitrificans genome has precluded the identification of more than eight protein spots as yet. A public accessible P. denitrificans 2‐DE protein database is currently built up at http://www.mpiib‐berlin.mpg.de/2D‐PAGE.
Incorporation of a new alkenyl‐based nonionic surfmer into acrylic latexes
Authors: Aramendia Esteban , Barandiaran María J. , De La Cal José C. , Grade Jo , Blease Trevor , Asua José M. 
Published: July 2004

AbstractThe mechanisms by which a new nonionic alkenyl‐based surfmer (Maxemul 5011™) was involved in acrylic emulsion polymerization were investigated. No proof of homopolymerization or of chain transfer to surfmer was obtained under the conditions studied. The effect of the initiator type, feeding time of the surfmer, particle size of the seed, and surfmer concentration, on kinetics and surfmer incorporation showed that the surfmer reacted mainly by copolymerization with the monomers in the outer shell of the polymer particles. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4202–4211, 2004
Synthesis of homopolymers and multiblock copolymers by the living ring‐opening metathesis polymerization of norbornenes containing acetyl‐protected carbohydrates with well‐defined ruthenium and molybdenum initiators
Authors: Miyamoto Yoshitaka , Fujiki Michiya , Nomura Kotohiro 
Published: July 2004

AbstractThe ring‐opening metathesis polymerization (ROMP) of norbornenes containing acetyl‐protected glucose [2,3,4,6‐tetra‐O‐acetyl‐glucos‐1‐O‐yl 5‐norbornene‐2‐carboxylate (1)] and maltose [2,3,6,2′,3′,4′,6′‐hepta‐O‐acetyl‐maltos‐1‐O‐yl 5‐norbornene‐2‐carboxylate (2)] was explored in the presence of Mo(N‐2,6‐iPr2C6H3)(CHCMe2Ph)(OtBu)2 (A), Ru(CHPh)(Cl)2(PCy3)2 (B; Cy = cyclohexyl), and Ru(CHPh)(Cl)2(IMesH2)(PCy3) (C; IMesH2 = 1,3‐dimesityl‐4,5‐dihydromidazol‐2‐ylidene). The polymerizations promoted by B and A proceeded in a living fashion with exclusive initiation efficiency, and the resultant polymers possessed number‐average molecular weights that were very close to those calculated on the basis of the monomer/initiator molar ratios and narrow molecular weight distributions (weight‐average molecular weight/number‐average molecular weight < 1.18) in all cases. The observed catalytic activity of B was strongly dependent on both the initial monomer concentration and the solvent employed, whereas the polymerization initiated with A was completed efficiently even at low initial monomer concentrations. The polymerization with C also took place efficiently, and even the polymerization with 1000 equiv of 1 was completed within 2 h. First‐order relationships between the propagation rates and the monomer concentrations were observed for all the polymerization runs, and the estimated rate constants at 25 °C increased in the following order: A > C > B. On the basis of these results, we concluded that ROMP with A was more suitable than ROMP with B or C for the efficient and precise preparation of polymers containing carbohydrates. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4248–4265, 2004
Orientation and relaxation of polymer–clay solutions studied by rheology and small‐angle neutron scattering
Authors: Malwitz Matthew M. , Butler Paul D. , Porcar Lionel , Angelette Drew P. , Schmidt Gudrun 
Published: July 2004

AbstractThe influence of shear on viscoelastic solutions of poly(ethylene oxide) (PEO) and clay [montmorillonite, i.e., Cloisite NA+ (CNA)] was investigated with rheology and small‐angle neutron scattering (SANS). The steady‐state viscosity and SANS were used to measure the shear‐induced orientation and relaxation of the polymer and clay platelets. Anisotropic scattering patterns developed at much lower shear rates than in pure clay solutions. The scattering anisotropy saturated at low shear rates, and the CNA clay platelets aligned with the flow, with the surface normal parallel to the gradient direction. The cessation of shear led to partial and slow randomization of the CNA platelets, whereas extremely fast relaxation was observed for laponite (LRD) platelets. These PEO–CNA networklike solutions were compared with previously reported PEO–LRD networks, and the differences and similarities, with respect to the shear orientation, relaxation, and polymer–clay interactions, were examined. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3102–3112, 2004
Cell proliferation and apoptosis in prostate tumors and adjacent non‐malignant prostate tissue in patients at different time‐points after castration treatment
Authors: Ohlson Nina , Wikström Pernilla , Stattin Pär , Bergh Anders 
Published: July 2004

AbstractBackgroundAndrogen ablation is the standard treatment for advanced prostate cancer but the short‐term cellular effects are largely unknown.MethodsSextant prostate biopsies were taken from 77 prostate cancer patients before and 1–10 days after castration treatment. Apoptosis, cell proliferation, and morphology were studied in malignant and non‐malignant tissue, using stereological and immunohistochemical methods.ResultsEpithelial cell proliferation was significantly decreased both in non‐malignant and malignant epithelium already 1 day after therapy. It remained low until day 7, but increased thereafter in the remaining non‐malignant epithelial cells and in some tumors. Epithelial cell apoptosis was significantly increased during the first week and then returned to basal levels. The maximal apoptotic indexes, seven‐ and two‐times the intact levels in the non‐malignant and malignant glands, respectively, were found at days 3–4 or even earlier in the tumors. Signs of tumor shrinkage such as glandular collapse and decreased tumor cell size were observed from day 3 in most tumors.DiscussionThe present study shows that the magnitude and kinetics of the response to castration in the normal human prostate is very similar to the response previously described in rodents. We also demonstrate that most human prostate tumors rapidly respond to castration indicating the need for further evaluation of when and how to best monitor the effects of hormone ablation therapy in prostate cancer patients. © 2004 Wiley‐Liss, Inc.
Ability of PSA‐positive circulating macrophages to detect prostate cancer
Authors: Herwig Ralf , Horninger Wolfgang , Rehder Peter , Klocker Helmut , Ramoner Reinhold , Thurnher Martin , Pinggera Germar M. , Gozzi Christian , Konwalinka Günther , Bartsch Georg 
Published: July 2004

AbstractBackgroundProstate‐specific antigen (PSA) is a widely used serum marker for prostate cancer, but has a poor specificity for early detection at levels below 10 ng/ml, because it can also result from benign conditions. Our aim was to determine the frequencies of circulating PSA+ macrophages in a blinded study and to examine the suitability of this new method for differentiating between benign and malignant prostate disease.MethodsBetween October 2002 and February 2003, 126 patients undergoing transrectal biopsy were enrolled in this study. Peripheral blood macrophages were stained for intracellular content of PSA in all patients. Ten patients' peripheral blood mononulear cells (PBMCs) were also supplementarily stained for cytokeratin (CK) and epithelial membrane antigen (EMA). Macrophages were analysed by flow cytometry. Patients were grouped according to their biopsy histology and bone scan results.FindingsBased on histological data, patients were classified as having no evidence of malignancy (NEM) (n = 59), prostatitis (n = 20), or localised prostate cancer (n = 37). Significantly higher levels of circulating PSA+ macrophages were found in prostate cancer compared to benign conditions. Calculating a 2% cut‐off level enabled the detection of localised prostate cancer with 89% sensitivity and 80% specificity. In a subset of patients (65%) with a serum PSA below 4 ng/ml and confirmed prostate cancer, the percentage of PSA+ macrophages was significantly higher compared to NEM and prostatitis. Macrophages of ten patients tested with prostate cancer contained significantly higher amounts of PSA, EMA, and CK compared to ten with NEM.InterpretationIntracellular PSA in combination with CK and EMA can be found in permeabilized blood macrophages, indicating phagocytosis of complete cancer cells. This study further suggests, that this new method might be suitable for differentiating between prostate cancer and benign conditions especially in patients with low serum PSA. © 2004 Wiley‐Liss, Inc.
Monitoring of skeletal progression of prostate cancer by GFP imaging, X‐ray, and serum OPG and PTHrP
Authors: Burton D.W. , Geller J. , Yang M. , Jiang P. , Barken I. , Hastings R.H. , Hoffman R.M. , Deftos L.J. 
Published: July 2004

AbstractBackgroundProstate cancers (PCas) produce factors that can serve as biomarkers for tumor metastasis and bone progression. Transduced GFP expression by cancer cells can be imaged to monitor therapy. We exploited both concepts by developing a GFP‐expressing PCa cell line that expresses PTHrP and studying it in an animal model of malignancy with methods that assess the skeletal progression of this tumor.MethodsWe developed a GFP‐producing PCa cell line by stable transduction of PC‐3 PCa cells. This PC‐3 variant was used to study tumor progression in an immunocompromised mouse model. Skeletal progression of the PCa cells and the effects of pamidronate administration were evaluated radiologically, fluorometrically, and by measurement of serum tumor markers.ResultsThe PC‐3 cells produced extensive bone lesions when injected into the tibia of immunocompromised mice. The skeletal progression of the PC‐3 cells could be monitored by GFP optical imaging, X‐ray, and by measurements of tumor products in serum, notably PTHrP and OPG. Pamidronate treatment reduced tumor burden as assessed at autopsy by imaging and biomarkers.ConclusionsPamidronate treatment exhibited anti‐tumor effects that were reflected by decreases in serum PTHrP, OPG, and by GFP and radiological imaging procedures. Imaging of GFP expression enables real‐time monitoring of tumor growth in the bone. PTHrP and OPG may be useful as tumor biomarkers for PCa that has metastasized to bone. This novel human PCa model can be used to study the clinical potential of diagnostic and therapeutic modalities in the skeletal progression of PCas. © 2004 Wiley‐Liss, Inc.
Castration triggers growth of previously static androgen‐independent lesions in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model
Authors: Johnson Mac A. , Iversen Philip , Schwier Phillip , Corn Angela L. , Sandusky George , Graff Jeremy , Neubauer Blake Lee 
Published: July 2004

AbstractBackgroundAndrogen‐deprivation remains the standard of care for metastatic prostate cancer, yet its total impact on the course of disease is incompletely established.MethodsWe have examined the long‐term effects of castration upon the progression of established cancer in the TRAMP transgenic mouse model of prostate cancer. Mice castrated at 15‐weeks of age, as well as intact littermates, were followed until spontaneous death from cancer.ResultsStatistical analyses of age‐at‐death versus primary tumor mass revealed that mice segregate into two categories of response to androgen‐deprivation. In Category One, the act of castration paradoxically triggers the growth of microscopic androgen‐independent lesions, as evidenced by a statistical synchronization of primary tumor growth. Delaying castration until 20‐weeks of age delays the synchronized growth of these tumors, as well as the deaths of the host mice. In Category Two, castration eliminates or substantially delays primary tumor growth, but fails to eliminate metastases. so that castration is found to impart no long‐term survival advantage.ConclusionsWe propose a two‐step model for the alteration of androgen signaling in prostate cancer capable of explaining the above paradoxical results, which is based upon the dualistic role of androgens as both survival and differentiation factors. This model makes specific predictions for clinical intervention that are discussed in light of published studies. © 2004 Wiley‐Liss, Inc.
Prostate specific membrane antigen (PSMA) is a tissue‐specific target for adenoviral transduction of prostate cancer in vitro
Authors: Kraaij R. , van Rijswijk A.L.C.T. , Oomen M.H.A. , Haisma H.J. , Bangma C.H. 
Published: July 2004

AbstractBackgroundAdenovirus binds to the coxsackievirus and adenovirus receptor (CAR) as a first step in the process of cellular infection. This dependence on CAR potentially limits the use of adenovirus in gene therapy, since CAR is expressed in many tissues of the body, and expression of CAR may be low or lost upon progression of certain tumors. These limitations may be overcome by transductional targeting of adenovirus towards other cell surface molecules. We have evaluated the pantumoral epithelial cell adhesion molecule (EpCAM) and prostate specific membrane antigen (PSMA) as possible targets for adenoviral transduction of prostate cancer cells.MethodsBispecific antibodies, constructed as conjugates between an anti‐adenovirus fiber knob Fab' fragment and anti‐EpCAM or anti‐PSMA monoclonal antibodies, were incubated with an eGFP‐expressing adenovirus to retarget this vector. A cell panel, that includes two prostate cancer cell lines and four non‐prostate control lines, were infected with serial dilutions of the retargeted vector and specificity of infection was determined.ResultsReceptor‐specific transduction was obtained for both EpCAM and PSMA. PSMA‐retargeting was shown to be selective for the prostate cancer cell lines.ConclusionsPSMA serves as a tissue‐specific target for adenoviral vectors and may be applicable for gene therapeutical treatment of prostate cancer. © 2004 Wiley‐Liss, Inc.
Theoretical study of the stability of wurtzite, zinc‐blende, NaCl and CsCl phases in group IIIB and IIIA nitrides
Authors: Mancera Luis , Rodríguez Jairo A. , Takeuchi Noboru 
Published: July 2004

AbstractThe relative stability of wurtzite, zinc‐blende, rock‐salt and CsCl structures and the possibility of high‐pressure phase transformations from wurtzite to rocksalt and from rocksalt to CsCl is of special interest. We present a comparative study of the stability of these phases for two Group IIIB‐nitrides (ScN, YN) and two Group IIIA‐nitrides (GaN, InN), in the framework of DFT. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Calibration of a pH sensitive buried channel silicon‐on‐insulator MOSFET for sensor applications
Authors: Ashcroft B. , Takulapalli B. , Yang J. , Laws G. M. , Zhang H. Q. , Tao N. J. , Lindsay S. , Gust D. , Thornton T. J. 
Published: July 2004

AbstractThe threshold voltage characteristics of a buried channel silicon‐on‐insulator MOSFET is examined in solutions of varying acidity. Experiments utilizing an integrated micro‐fluidic channel exhibit a variation in threshold voltage that appears approximately linear with pH in the range from pH 4 to pH 7, with a sensitivity of ∼1 V per pH unit. Charge configuration changes in the vicinity of the MOSFET inversion layer due to protonation/deprotonation of the device surface is proposed as an explanation for the observed shifts in threshold voltage. When the pH range is expanded we observe a non‐linear relationship bet‐ ween pH and the threshold voltage of the device, this behavior is explained in terms of deprotonation of the different species of the native oxide surface, Numerical simulations of the MOSFET demonstrate that the threshold voltage sensitivity corresponds to an additional surface positive fixed charge density of ∼ 1 × 1010 cm–2 for each pH unit. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Metabolism of 1‐{3‐[3‐(4‐cyanobenzyl)‐3H‐imidazol‐4‐yl]‐propyl}‐3‐(6‐methoxypyridin‐3‐yl)‐1‐(2‐trifluoromethylbenzyl)thiourea (YH3945), a novel anti‐cancer drug, in rats using the 14C‐labeled compound
Authors: Lee Jaeick , La Sookie , Ahn Byung Rak , Jeong Tae Cheon , Kim Dong‐Hyun 
Published: July 2004

AbstractThe metabolism of a novel anti‐cancer agent, 1‐{3‐[3‐(4‐cyanobenzyl)‐3H‐imidazol‐4‐yl]‐propyl}‐3‐(6‐methoxypyridin‐3‐yl)‐1‐(2‐trifluoromethylbenzyl)thiourea (YH3945), was investigated in rats. Bile, plasma, feces, and urine were collected and analyzed by a high‐performance liquid chromatography (HPLC) system equipped with ultraviolet (UV), mass spectrometric, and radioactivity detectors. After intravenous dosing, mean radiocarbon recovery was 74.4 ± 1.3% with 62.4 ± 1.2% in the feces and 12.0 ± 0.5% in the urine. Biliary excretion of the radioactivity for the first 24 h period was approximately 32%, suggesting that YH3945 is cleared by hepatobiliary excretion. YH3945 was extensively metabolized to 21 different metabolites including glucuronide conjugates, and structures of the metabolites were elucidated based on MSn and NMR spectral analyses. The major metabolic pathways in the rat were identified as O‐demethylation of methoxypyridine, N‐debenzylation of imidazole, and hydroxylation. Cyclic metabolites were also identified; concomitant demethylation in the methoxypyridine moiety and hydroxylation at the C16 position might destroy the chemical stability of the compound and subsequently lead to non‐enzymatic cyclization. Cyclic metabolites were characteristic of YH3945, and a non‐enzymatic reaction mechanism for the formation of cyclic metabolites was postulated. Copyright © 2004 John Wiley & Sons, Ltd.
Analysis of neutral drugs in human plasma by fluoride attachment in liquid chromatography/negative ion electrospray tandem mass spectrometry
Authors: Sheen J. F. , Her G. R. 
Published: July 2004

AbstractThe analysis of several neutral drugs, mephenesin, guaifenesin, simvastatin, podophyllotoxin and inositol, was accomplished by negative ion electrospray ionization mass spectrometry (ESI‐MS) using adduct formation with three different halide ions. The fluoride, chloride and bromide adducts of the selected drugs exhibited intense signals in negative ion ESI. Under collision‐induced dissociation, the major product ions of bromide and chloride adducts were the nonspecific bromide and chloride anions, respectively. In contrast, fluoride adducts produced strong [MH]− ions as well as product ions with good intensity. Fluoride attachment liquid chromatography/negative ion electrospray tandem mass spectrometry (LC/ESI‐MS/MS) was applied to the analysis of the selected neutral drugs in human plasma. Detection limits in the range of 0.025–0.05 ng/mL were achieved using 0.5 mL plasma. Good linearity was observed for each of the drugs examined in human plasma over the range of 0.05–50 ng/mL. Copyright © 2004 John Wiley & Sons, Ltd.
Proteome analysis in the bovine adrenal medulla using liquid chromatography with tandem mass spectrometry
Authors: Jalili Pegah R. , Dass Chhabil 
Published: July 2004

AbstractLiquid chromatography/mass spectrometry (LC/MS)‐based proteomics has been used to identify soluble proteins in the bovine adrenal medulla. This gland is a major source of hormones, opioids, neurotransmitters, and several vital proteins. The adrenal medulla proteins were first purified using ammonium sulfate precipitation. The resulting proteins were then pre‐fractionated with a C‐4 high‐peformance liquid chromatography (HPLC) column. Each 2‐min HPLC fraction was digested with trypsin, and separated further and analyzed using capillary liquid chromatography/tandem mass spectrometry (capLC/nanospray‐MS/MS) to map the proteome of the adrenal medulla. The parent mass and sequence ion information thus obtained for tryptic peptides was used to search the NCBInr database using the SEQUEST search engine. A total of 195 proteins were identified, of which 71 had good scores (delta correlation value greater than 0.1, preliminary score above 200, and cross‐correlation value above 2.5). The prominent proteins thus identified are secretogranin I precursor, chromogranin A, proenkephalin A precursor, myosin X, hemoglobin beta chain, hemoglobin alpha chain, heat shock protein 10 kDa, and replicase. Copyright © 2004 John Wiley & Sons, Ltd.