bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evaluation of DISC‐GMCSF for the treatment of breast carcinoma
Authors: Loudon Peter T. , McLean Cornelia S. , Martin Gilly , Curry Jayne , Leigh Shaw M. , Hoogstraten Conny , Verdegaal Els , Osanto Susanne 
Published: April 2003

AbstractBackgroundDISC‐hGMCSF is a gH‐deleted HSV‐2 based vector expressing human GM‐CSF that has entered clinical trials for the therapy of metastatic melanoma. To determine whether this product also has potential to treat breast carcinoma, a series of in vitro and in vivo studies were made.MethodsBreast carcinoma cell lines and primary cultures of breast carcinoma cells were infected with DISC‐GFP or DISC‐human‐GMCSF (DISC‐hGMCSF) and the number of GFP‐positive cells and GM‐CSF yields were determined. In vivo efficacy of DISC‐murine‐GMCSF (DISC‐mGMCSF) in combination with systemic chemotherapy was assessed in the murine 4T1 breast carcinoma model by direct injection into subcutaneous tumours.ResultsDISC‐hGMCSF was able to infect all breast carcinoma cell lines and the majority of primary breast carcinoma cultures with high efficiency, although culture‐to‐culture variability in infectability was noted in the latter. In the MCF‐7 breast carcinoma cell line, expression of hGMCSF was found to peak over the first 24 h post‐infection and drop to background levels by 7 to 14 days. In the 4T1 murine breast tumour model, injection of subcutaneous tumours led to a delay in tumour growth and, in rare cases, complete regression of visible tumour. DISC‐mGMCSF and DISC‐LacZ showed similar levels of efficacy. When mice were given simultaneous 5FU chemotherapy the effectiveness of DISC‐mGMCSF treatment was undiminished, and up to three out of ten mice showed complete absence of visible tumour.ConclusionsDISC‐hGMCSF is able to infect human breast carcinoma cells at high efficiency and express GM‐CSF. DISC‐mGMCSF demonstrated efficacy in the murine 4T1 model, even during concomitant chemotherapy. Taken together these results indicate that DISC‐hGMCSF may have potential for the treatment of breast carcinoma. Copyright © 2003 John Wiley & Sons, Ltd.
A DNA vaccine containing inverted terminal repeats from adeno‐associated virus increases immunity to HIV
Authors: Xin Ke‐Qin , Ooki Takaaki , Jounai Nao , Mizukami Hiroaki , Hamajima Kenji , Kojima Yoshitsugu , Ohba Kenji , Toda Yoshihiko , Hirai Syu‐Ichi , Klinman Dennis M. , Ozawa Keiya , Okuda Kenji 
Published: April 2003

AbstractBackgroundDNA vaccines have been used to induce both humoral and cellular immune responses against infectious microorganisms. This study explores whether DNA vaccine immunogenicity can be improved by introducing inverted terminal repeats (ITRs) from adeno‐associated virus (AAV) into the regulatory region of the DNA plasmid.MethodsCMV promoter‐driven HIV Env expressing plasmid (pCMV‐HIV) and the pCMV‐HIV plasmid introduced ITRs (pITR/CMV‐HIV) were transfected in HEK293 cells with LipofectAmine. The HIV Env expression was quantified with Western blot. Fifty µg of pCMV‐HIV or pITR/CMV‐HIV plasmid with RIBI adjuvant were immunized to BALB/c mice on days 0, 14 and 28 by intramuscular route, and HIV‐specific serum IgG titer was detected 2, 6, 10, 14 and 18 weeks after the first immunization. HIV‐specific tetramer assay and HIV‐specific IFN‐γ ELIspot assay were performed 1 week after the last immunization. The immune mice were intravenously challenged with a vaccinia virus expressing the HIV env gene 1 week after the last immunization.ResultsSignificantly higher level of HIV Env expression was achieved by pITR/CMV‐HIV plasmid. BALB/c mice immunized with pITR/CMV‐HIV plasmid generated significantly higher HIV‐specific antibody, higher cellular immune responses and lower viral loading than animals immunized with pCMV‐HIV plasmid.ConclusionsAAV ITRs enhance CMV‐dependent up‐regulation of transgene expression and immunogenicity of DNA vaccine. Copyright © 2002 John Wiley & Sons, Ltd.
Local tumour irradiation enhances the anti‐tumour effect of a double‐suicide gene therapy system in a murine glioma model
Authors: Desaknai Szilvia , Lumniczky Katalin , Esik Olga , Hamada Hirofumi , Safrany Geza 
Published: April 2003

AbstractBackgroundGliomas are invasive malignant tumours with poor prognosis. Combination of gene directed enzyme pro‐drug therapy with existing treatment modalities might open new therapeutic potentials.MethodsMurine glioma 261 (Gl261) cells were transduced with an adenoviral vector (Adex‐CAUPTK) encoding both uracil phosphoribosyltransferase and thymidine kinase genes which sensitise cells to 5‐fluorouracil (5‐FU) and ganciclovir (GC), respectively. Subcutaneous or intracranial tumours were established in C57Bl mice by transplanting drug‐sensitising gene containing Gl261 cells. In vitro growing cells or established tumours were treated with 5‐FU, GC and ionising radiation either alone or in combinations. Finally, subcutaneous tumours were established with non‐transduced cells, directly injected with Adex‐CAUPTK, and mice were treated with combinations of 5‐FU, GC and tumour irradiation.ResultsIn vitro treatment of transduced Gl261 cells with both 5‐FU and GC showed enhanced cytotoxic effect compared with single agents. Combination of drug treatments with irradiation greatly increased cytotoxicity. In subcutaneous and intracranial tumours double‐agent treatment was more effective than a single drug. Combination with local irradiation highly improved the anti‐tumour effect (90–100% survival) even when only part of the tumour cells carried drug‐sensitising genes (40–50% survival at 10% rate). Treatment of established tumours with direct intra‐tumour Adex‐CAUPTK inoculations and intraperitoneal 5‐FU, GC injections slowed down tumour progression that was further enhanced by local irradiation.ConclusionThe combination of double‐suicide gene therapy with local irradiation is a promising tool to eradicate small, residual tumours. Copyright © 2002 John Wiley & Sons, Ltd.
Gene therapy of streptozotocin‐induced diabetes by intramuscular delivery of modified preproinsulin genes
Authors: Croze France , Prud'homme Gérald J. 
Published: April 2003

AbstractBackgroundDespite improvements in insulin preparation and delivery, physiological normoglycemia is not easily achieved in diabetics. Therefore, there has been considerable interest in developing gene therapy approaches to supply insulin. We studied a nonviral muscle‐based method of gene therapy and demonstrated that it could prevent hyperglycemia in murine streptozotocin (STZ)‐induced diabetes.MethodsA plasmid encoding mouse furin‐cleavable preproinsulin II cDNA (FI), or its B10‐analogue (B10FI), and a plasmid encoding furin were coinjected into muscle of CD‐1 mice, who were treated a day later with STZ to induce diabetes. Electroporation was applied to increase gene transfer. Blood glucose was measured in fed and fasting mice, and fasting plasma insulin was measured by radioimmunoassay. The form of insulin produced and the presence of C‐peptide were analyzed by gel filtration chromatography.ResultsA B10FI plasmid codelivered with a furin plasmid reduced fed and fasting blood glucose levels in STZ‐treated diabetic mice. The (pro)insulin levels in plasma were increased by up to 70‐fold versus blank plasmid‐treated diabetic mice. The administration of FI with furin was less effective. (Pro)insulin levels were greatly increased by using two plasmids carrying different promoter elements (CMV and SV40). Insulin was identified in muscle cells by immunohistochemistry. In plasma, 40–70% of the (pro)insulin was processed to the mature form and free C‐peptide was identified. Insulin gene‐treated mice had improved growth rates and appeared healthier. A single injection of B10FI with SV40Furin DNA increased plasma (pro)insulin for at least 8 weeks and reduced fed blood glucose levels for 5 weeks and fasting levels for 8 weeks.ConclusionsThis is the first report that electroporation‐enhanced intramuscular gene therapy with B10FI can prevent hyperglycemia in murine STZ‐induced diabetes. Gene therapy using various routes and methods of furin‐cleavable insulin gene delivery has been previously explored but, in muscle, results comparable to ours have not been reported. Copyright © 2002 John Wiley & Sons, Ltd.
Discrimination and classification of adulterants in maple syrup with the use of infrared spectroscopic techniques
Authors: Paradkar M M , Sivakesava S , Irudayaraj J 
Published: April 2003

AbstractFood adulteration is a profit‐making business for some unscrupulous manufacturers. Maple syrup is a soft target of adulterators owing to its simplicity of chemical composition. In this study the use of Fourier transform infrared (FTIR) spectroscopy and near‐infrared (NIR) spectroscopy to detect adulterants such as cane and beet invert syrups as well as cane and beet sugar solutions in maple syrup was investigated. The FTIR spectrum of adulterated samples was characterised and the regions 800–1200 cm−1 (carbohydrates) and 1200–1800 and 2800–3200 cm−1 (carbohydrates, carboxylic acids and amino acids) were used for detection. The region between 1100 and 1660 nm in the NIR spectrum was used for analysis. Linear discriminant analysis (LDA) and canonical variate analysis (CVA) were used for discriminant analysis, while partial least squares (PLS) and principal component regression (PCR) were used for quantitative analysis. FTIR was more accurate in predicting adulteration using two different regions (R2 > 0.93 and >0.98) compared with NIR (R2 > 0.93). Classification and quantification of adulterants in maple syrup show that NIR and FTIR can be used for detecting adulterants such as pure beet and cane sugar solutions, but FTIR was superior to NIR in detecting invert syrups.© 2003 Society of Chemical Industry
Induced lactic acid fermentation of untreated green olives of the Conservolea cultivar by Lactobacillus pentosus
Authors: Panagou Efstathios Z , Tassou Chrysoula C , Katsaboxakis Constantinos Z 
Published: April 2003

AbstractInoculation of untreated green olives of the Conservolea cultivar (Olea europea media rotunda) with a commercial strain of Lactobacillus pentosus with/without glucose supplement was studied. Despite an initial loss in viability of 0.5 log cycles on average, due to lack of adaptation of the starter to the saline environment of the brine, cultures grew well and initiated an accelerated fermentation process. Inoculation reduced the survival period of Enterobacteriaceae, and consequently potential spoilage, and caused a quicker acidification of brines and decrease in pH compared with control uninoculated processes. The diffusion of phenolic compounds was slow, hindered by the epidermis of the fruits, and had no effect on the growth of the starter. HPLC analysis revealed that lactic and acetic acids were among the end‐products during the fermentation of green olives. Citric, tartaric and malic acids were also detected but at much lower concentrations. Results obtained from this work can be applied directly to industry for the effective use of starter cultures on natural fermentation processes of green olives without prior lye treatment.© 2003 Society of Chemical Industry
Temperature–time relationships for thermal inactivation of pectinesterases in orange juice
Authors: Lee Jan‐Yee , Lin Yeong‐Shenn , Chang Hung‐Min , Chen Whitney , Wu Ming‐Chang 
Published: April 2003

AbstractThe first‐order kinetic model of a two‐component system was applied to calculate the necessary parameters using the commercial Mathcad program package during the experimental thermal pasteurisation of Valencia orange juice. Thermostable and thermolabile pectinesterases, accounting for 6.6 and 93.4% of the total enzyme population in the juice respectively, showed a 5.63 °C Zs value and a 9.54 °C Zl value respectively from the thermal destruction curves at temperatures ranging from 75 to 90 °C. The calculated Zs values were consistent with the literature values for Valencia orange juice. The calculated and experimental non‐linear thermal pasteurisation curves for orange juice were also in good agreement at temperatures between 75 and 90 °C.© 2003 Society of Chemical Industry
Detection of Lathyrus sativus in processed chickpea‐ and red gram‐based products by thin layer chromatography
Authors: Paradkar Manish M , Singhal Rekha S , Kulkarni Pushpa R 
Published: April 2003

AbstractExcessive consumption of Lathyrus sativus leads to crippling, irreversible paralysis of both lower limbs, mainly in males. This is attributed to the presence of a non‐protein amino acid, β‐N‐oxalyl‐L‐2,3‐diaminopropionic acid or β‐N‐oxalylamino‐L‐alanine. Using a thin layer chromatography method developed in our laboratory, adulteration of chickpea and red gram with L sativus in pressure‐cooked batters could be detected at levels of 100 and 200 g kg−1 respectively. When processed as a curried liquid dal, L sativus could be detected at 200 g kg−1 in chickpea and 100 g kg−1 in red gram. Processing into fried bhajiyas resulted in a detection limit of 200 g kg−1 in both red gram and chickpea.© 2003 Society of Chemical Industry
Species identification of red and brown seaweeds using ITS ribosomal DNA amplification and RFLP patterns
Authors: Antoine Elisabeth , Fleurence Joël 
Published: April 2003

AbstractThe identity of five macroalgae used as sea vegetables or food ingredients has been determined by amplification of the ribosomal DNA ITS region and RFLP analysis. This allows the detection of specificity patterns for each species and provides an alternative method, when morphological or biochemical methods fail, for control of their use as food ingredients. Alga‐specific PCR primers have been used to determine the ITS rDNA sequences of DNAs extracted from dried and ground algae up to 5 years old. The seaweeds studied were the red algae Palmaria palmata (dulse), Porphyra umbilicalis (nori), and Chondrus crispus (pioca) and the brown algae Himanthalia elongata (sea spaghetti) and Laminaria sp (konbu). Total genomic DNA suitable for amplification was extracted from the alga powder following the CTAB method. This methodology allowed the sequencing of the amplified product and the drawing of theoretical restriction maps useful in the choice of restriction enzymes for RFLP analysis. Enzymes that appeared useful included Mbo I and Alu I. Cutting with a single enzyme was sufficient to obtain characteristic patterns for the red algae P palmata, P umbilicalis and C crispus. For the two brown algae H elongata and Laminaria sp the ITS rDNA sequence showed a lack of suitable restriction site, contrary to other species for which characteristic patterns were obtained.© 2003 Society of Chemical Industry
Leakage of metabolites from tissue biopsies can result in large errors in quantitation by MRS
Authors: Bourne Roger , Dzendrowskyj Theresa , Mountford Carolyn 
Published: April 2003

AbstractThe leakage of metabolites from frozen and thawed tissue biopsies was measured semi‐quantitatively by high‐field (8.5 T) proton MRS. Human prostate and rat brain tissue specimens, frozen within 1 min of collection, lost significant and variable amounts of diagnostic metabolites immediately upon thawing. For prostate tissue 30–50% of initial total choline compounds, total creatines and citrate were detected in the collection buffer immediately after thawing. The widely used protocol for MR assessment of tissue biopsies, which involves washing of thawed tissue samples in fresh buffer, results in loss of large and unpredictable amounts of possibly diagnostic metabolites prior to MRS. This reduces the reproducibility of MR analysis of tissue biopsies and compromises the reliable identification of MR spectral patterns diagnostic of tissue pathology. The problem can be avoided by minimizing the volume of storage buffer, omitting tissue washing and performing MRS measurements on the tissue immersed in the original storage buffer. Copyright © 2003 John Wiley & Sons, Ltd.
Scaled boundary finite‐element analysis of a non‐homogeneous elastic half‐space
Authors: Doherty James P. , Deeks Andrew J. 
Published: May 2003

AbstractAs a result of stresses experienced during and after the deposition phase, a soil strata of uniform material generally exhibits an increase in elastic stiffness with depth. The immediate settlement of foundations on deep soil deposits and the resultant stress state within the soil mass may be most accurately calculated if this increase in stiffness with depth is taken into account. This paper presents an axisymmetric formulation of the scaled boundary finite‐element method and incorporates non‐homogeneous elasticity into the method. The variation of Young's modulus (E) with depth (z) is assumed to take the form E=mEzα, where mE is a constant and αis the non‐homogeneity parameter. Results are presented and compared to analytical solutions for the settlement profiles of rigid and flexible circular footings on an elastic half‐space, under pure vertical load with αvarying between zero and one, and an example demonstrating the versatility and practicality of the method is also presented. Known analytical solutions are accurately represented and new insight regarding displacement fields in a non‐homogeneous elastic half‐space is gained. Copyright © 2003 John Wiley & Sons, Ltd.
Rate‐dependent projection operators for frictional contact constraints
Authors: Araki Y. , Hjelmstad K.D. 
Published: May 2003

AbstractWe develop rate‐dependent regularization approaches for three‐dimensional frictional contact constraints based on the Kelvin and Maxwell viscoelastic constitutive models. With the present regularization schemes, we aim to provide a basis to better model friction and to stabilize the contact analysis while keeping the contact model as simple as possible. The key feature of the regularization approaches, implemented using an implicit time integrator, is that one can recover in the limit the widely used rate‐independent elastoplastic regularization framework without encountering numerical difficulties. Intermediate contact tractions are defined in terms of the relative displacement, the relative velocity, and the regularization parameters. The projection operators operate on the intermediate tractions and yield contact tractions that satisfy all the discretized contact constraints. The use of projection operators allows a systematic implementation of the present regularization schemes. Through numerical simulations, we observed that the Maxwell‐type regularization effectively avoids convergence problems, even for relatively large time step sizes, while the Kelvin‐type regularization does not. Copyright © 2003 John Wiley & Sons, Ltd.
Boundary element analysis in thermoelasticity with and without internal cells
Authors: Gao Xiao‐Wei 
Published: May 2003

AbstractIn this paper, a set of internal stress integral equations is derived for solving thermoelastic problems. A jump term and a strongly singular domain integral associated with the temperature of the material are produced in these equations. The strongly singular domain integral is then regularized using a semi‐analytical technique. To avoid the requirement of discretizing the domain into internal cells, domain integrals included in both displacement and internal stress integral equations are transformed into equivalent boundary integrals using the radial integration method (RIM). Two numerical examples for 2D and 3D, respectively, are presented to verify the derived formulations. Copyright © 2003 John Wiley & Sons, Ltd.
On the construction of blending elements for local partition of unity enriched finite elements
Authors: Chessa Jack , Wang Hongwu , Belytschko Ted 
Published: May 2003

AbstractFor computational efficiency, partition of unity enrichments are preferably localized to the sub‐domains where they are needed. It is shown that an appropriate construction of the elements in the blending area, the region where the enriched elements blend to unenriched elements, is often crucial for good performance of local partition of unity enrichments. An enhanced strain formulation is developed which leads to good performance; the optimal rate of convergence is achieved. For polynomial enrichments, it is shown that a proper choice of the finite element shape functions and partition of unity shape functions also improves the accuracy and convergence. The methods are illustrated by several examples. The examples deal primarily with the signed distance function enrichment for treating discontinuous derivatives inside an element, but other enrichments are also considered. Results show that both methods provide optimal rates of convergence. Copyright © 2003 John Wiley & Sons, Ltd.
How strategy, culture, and improved service delivery reshaped Monsanto's international assignment program
Authors: Schaefer Joyce , Hannibal Ed , O'Neill James 
Published: May 2003

AbstractEffective implementation of change requires great sensitivity to an organization's formal and informal
ways of functioning. In its effort to rationalize its practices and policies affecting its expatriate workforce,
Monsanto covered all those bases—leading to a smooth adoption of changes that will help the company retain
and benefit from the knowledge of this important segment of a global company's workforce. ©
2003 Wiley Periodicals, Inc.
Analysis of genetic alterations, classified according to their DNA ploidy pattern, in the progression of colorectal adenomas and early colorectal carcinomas
Authors: Sugai Tamostu , Takahashi Hiroshi , Habano Wataru , Nakamura Shin‐ichi , Sato Kimihiko , Orii Seishi , Suzuki Kazuyuki 
Published: May 2003

AbstractDNA aneuploidy is a biological marker of the oncogenic potential of colorectal adenomas. The accumulation of genetic alterations of cancer‐related genes is also essential for colorectal carcinogenesis. However, it is unclear whether there is any relationship between these genetic alterations and the DNA ploidy of colon tumour cells in the progression of colorectal adenomas and early colorectal carcinomas. Here we have studied the DNA ploidy state and genetic alterations occurring in colorectal tumours using the crypt isolation technique. Crypts isolated from a total of 106 colorectal tumors (adenoma, 93; early carcinoma, 13) were examined using a combination of flow cytometric analysis of DNA content, polymerase chain reaction–microsatellite assay, and single‐strand conformation polymorphism assay for evidence of chromosomal allelic imbalance (AI; 17p; 5q; 18q) or p53 gene mutation. In addition, we examined microsatellite instability (MSI) with BAT 26 primer sets. DNA multiploidy was infrequently detected in colorectal adenomas (15.1%), in contrast to early carcinomas (46.2%). There was a significant difference in the incidence of AI of chromosome 18q between diploid adenomas and aneuploid populations of multiploid adenomas (18.1% vs 57.1%, p = 0.0043). Mutation of p53 was also found more frequently in aneuploid populations of early multiploid colorectal carcinomas than in early diploid colorectal carcinomas (66.7% vs 0%, p = 0.021). MSI was found in only 2 of 93 adenomas, with no MSI detected in early colorectal cancers. The two MSI‐positive adenomas were diploid. We subdivided multiploid adenomas into two groups: those with a low or a high DNA index (DI). The incidence of genetic alterations of high‐DI adenomas did not differ from those of low‐DI adenomas. Allelic imbalance involving loci on chromosome 18q and mutations of p53 seems to be associated with the progression of diploidy to multiploidy in colorectal tumours. On the other hand, MSI may be associated with the development of some diploid tumours. In addition, the incidence of genetic alterations in the colorectal adenomas that we examined appears to be independent of the tumour's DNA index. Copyright © 2003 John Wiley & Sons, Ltd.