bluuebunny/crossref_metadata_2025 huggingface dataset:
Markers of cellular proliferation are expressed in cortical tubers
Authors: Lee Allana , Maldonado Michelle , Baybis Marianna , Walsh Christopher A. , Scheithauer Bernd , Yeung Raymond , Parent Jack , Weiner Howard L. , Crino Peter B.
Published: April 2003

p34cdc2, collapsin response mediator protein 4 (CRMP4), doublecortin (DCX), HuD, and NeuN expression was assessed in tuber (n = 16) and subependymal giant cell astrocytoma (SEGA; n = 6) specimens in tuberous sclerosis complex to define the developmental phenotype and lineage of giant cells (CGs) in these lesions. Many GCs exhibited HuD and NeuN immunolabeling suggesting a differentiated neural phenotype. Giant cells in tubers, SEGAs and subependymal nodules in the Eker rat model of TSC expressed CRMP4 and DCX. Tubers and SEGAs exhibit a heterogeneous profile of differentiation and may share a common cellular lineage. Tubers may contain a subpopulation of newly generated cells. Ann Neurol 2003;53:668–673
New T2 lesions enable an earlier diagnosis of multiple sclerosis in clinically isolated syndromes
Authors: Dalton Catherine M. , Brex Peter A. , Miszkiel Katherine A. , Fernando Kryshani , MacManus David G. , Plant Gordon T. , Thompson Alan J. , Miller David H.
Published: April 2003

In clinically isolated syndromes, the new McDonald criteria for multiple sclerosis diagnosis require new gadolinium‐enhancing lesions for dissemination in time at a 3‐month follow‐up magnetic resonance imaging scan. In a cohort of 56 patients, these criteria were specific (95%) but less sensitive (58%) for clinically definite multiple sclerosis at 3 years. If new T2 lesions were allowed as an alternative for dissemination in time, sensitivity increased (74%) with maintained specificity (92%), enabling an accurate diagnosis of multiple sclerosis in more patients. Ann Neurol 2003;53:673–676
Using a modified standard microscope to generate virtual slides
Authors: Romer David J. , Yearsley Kurtis H. , Ayers Leona W.
Published: April 2003

A standard microscope was reconfigured as a virtual slide generator by adding a Prior Scientific H101 robotic stage with H29 controller and 0.1‐μm linear scales and a Hitachi HV‐C20 3CCD camera. Media Cybernetics Image Pro Plus version 4 (IP4) software controlled stage movement in the X‐, Y‐, and Z‐axis, whereas a Media Cybernetics Pro‐Series Capture Kit captured images at 640 × 480 pixels. Stage calibration, scanning algorithms, storage requirements, and viewing modes were standardized. IP4 was used to montage the captured images into a large virtual slide image that was subsequently saved in TIF or JPEG format. Virtual slides were viewed at the workstation using the IP4 viewer as well as Adobe Photoshop and Kodak Imaging. MGI Zoom Server delivered the virtual slides to the Internet, and MicroBrightField's Neuroinformatica viewing software provided a browser‐based virtual microscope interface together with labeling tools for annotating virtual slides. The images were served from a Windows 2000 platform with 2 GB RAM, 500 GB of disk storage, and a 1.0 GHz P4 processor. To conserve disk space on the image server, TIF files were converted to the FlashPix (FPX) file format using a compression ratio of 10:1. By using 4×, 10×, 20×, and 40× objectives, very large gigapixel images of tissue whole‐mounts and tissue arrays with high quality and morphologic detail are now being generated for teaching, publication, research, and morphometric analysis. Technical details and a demonstration of our system can be found on the Web at http://virtualmicroscope.osu.edu. Anat Rec (Part B: New Anat) 272B:91–97, 2003. © 2003 Wiley‐Liss, Inc.
Hierarchical Linear Modeling in Salary Equity Studies
Authors: Loeb Jane W.
Published: April 2003

A hierarchical linear model is compared with an ordinary least squares model for conducting salary‐equity studies.
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

Background

DISC‐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.

Methods

Breast 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.

Results

DISC‐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.

Conclusions

DISC‐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

Background

DNA 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.

Methods

CMV 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.

Results

Significantly 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.

Conclusions

AAV 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

Background

Gliomas are invasive malignant tumours with poor prognosis. Combination of gene directed enzyme pro‐drug therapy with existing treatment modalities might open new therapeutic potentials.

Methods

Murine 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.

Results

In 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.

Conclusion

The 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

Background

Despite 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.

Methods

A 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.

Results

A 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.

Conclusions

This 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

Food 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

Inoculation 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

The 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

Excessive 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

The 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

The 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

As 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

We 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

In 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

For 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

Effective 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

DNA 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.
Expression of apoptosis regulators in cutaneous T‐cell lymphoma (CTCL) cells
Authors: Zhang Chun‐Lei , Kamarashev Jivko , Qin Jian‐Zhong , Burg Günter , Dummer Reinhard , Döbbeling Udo
Published: May 2003

This study examined cutaneous T‐cell lymphoma (CTCL) cell lines and cutaneous lesions for the presence of Bcl‐2 gene family members and found that the two apoptosis‐inhibiting members Bcl‐xL and Mcl‐1 and the two apoptosis‐supporting members Bad and Bax were expressed. However, Bad was at least partially inactivated by phosphorylation. In skin lesions, the translocation of Bad from the nucleus to the cytoplasm may reflect the Bad inactivation by phosphorylation identified in vivo. Bax is also ineffective, as the non‐steroidal anti‐inflammatory drug sulindac, whose cytotoxic effect is mediated by Bax, could not induce apoptosis in CTCL cell lines. The expression of Bcl‐2, Bcl‐xL, and Mcl‐1 may therefore be sufficient to guarantee the survival of malignant CTCL cells. The Bcl‐x, Mcl‐1, Bad, and Bax proteins were also expressed in all CTCL skin lesions tested. In two patients from whom two biopsies from two different time points of the disease were available, a significant increase in Mcl‐1 expression was found in the later‐stage skin lesion. Overexpression of Mcl‐1 and synthesis of non‐functional Bax may be responsible for the resistance of CTCL cells to the anti‐cancer drugs chlorambucil and sulindac. Copyright © 2003 John Wiley & Sons, Ltd.
β‐Catenin mutations in pulmonary blastomas: association with morule formation
Authors: Sekine Shigeki , Shibata Tatsuhiro , Matsuno Yoshihiro , Maeshima Arafumi , Ishii Genichiro , Sakamoto Michiie , Hirohashi Setsuo
Published: May 2003

To elucidate the contribution of β‐catenin gene mutation to the development of pulmonary blastomas, we analysed mutations in three well‐differentiated fetal adenocarcinomas (WDFAs) and six biphasic pulmonary blastomas (BPBs). For comparison, eight clear‐cell adenocarcinomas with fetal lung features were also examined. β‐Catenin gene mutations were found in all three WDFAs, two BPBs, and none of the clear‐cell adenocarcinomas with fetal lung features. All tumours with mutations had a common histological feature, namely morule formation, and showed a characteristic heterogeneous β‐catenin expression pattern that was revealed by immunohistochemistry. Strong nuclear/cytoplasmic expression of β‐catenin was seen in clustered cells in the morular areas and in single cells in glands, and was associated with neuroendocrine differentiation. As β‐catenin mutations are rare among lung tumours, this distinctive genetic feature, which is also immunohistochemically detectable as overexpression with a heterogeneous pattern, has diagnostic significance. The presence of this common genetic alteration found in both WDFA and BPB implies a histogenetic linkage between these tumours. Copyright © 2003 John Wiley & Sons, Ltd.
The attractive Achilles heel of germ cell tumours: an inherent sensitivity to apoptosis‐inducing stimuli
Authors: Spierings Diana CJ , de Vries Elisabeth GE , Vellenga Edo , de Jong Steven
Published: May 2003

Testicular germ cell tumours (TGCTs) are extremely sensitive to cisplatin‐containing chemotherapy. The rapid time course of apoptosis induction after exposure to cisplatin suggests that TGCT cells are primed to undergo programmed cell death as an inherent property of the cell of origin. In fact, apoptosis induction of germ cells in the testis is an important physiological mechanism to control the quality and quantity of the gametes produced. Although p53 protein is highly expressed in the majority of TGCTs, almost no p53 mutations have been detected. Interestingly, p53 overexpression is associated with loss of p21 and gain of mdm2 expression, which might indicate a partial loss in functionality of the p53 regulatory pathway in TGCTs. Besides p21, TGCTs often show low expression of other proteins involved in the regulation of cell cycle progression, such as the retinoblastoma protein and members of the INK4 family. It can be postulated that the deregulated G1–S phase checkpoint results in premature entry into the S phase upon DNA damage. In addition to Bcl‐2 family members that are involved in the regulation of germ cell apoptosis in the normal testis via the mitochondrial death pathway, the Fas death pathway is also known to regulate apoptosis of germ cells in the testis. Since chemotherapy has been shown to activate the Fas death pathway and TGCTs co‐express both Fas and its ligand FasL, TGCT cells might undergo apoptosis upon cisplatin treatment via autocrine or paracrine activation of the Fas system by FasL. The hypothesis suggested here is that the lack of cell cycle arrest following a cisplatin‐containing treatment, together with the activation of the Fas death pathway and the mitochondrial death pathway, explains the rapid and efficient apoptosis of TGCT cells. Defining the mechanisms involved in the cisplatin sensitivity of TGCTs will provide tools to increase cisplatin sensitivity in other human tumours with acquired or intrinsic resistance. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of ionic dissociation of membrane polymer on pervaporation performance
Authors: Iwatsubo Takashi , Masuoka Toshio , Mizoguchi Kensaku
Published: April 2003

Pervaporation of a water/alcohol mixture through a membrane which has ion‐exchange capacity has been investigated. Theoretical equations are introduced which relate the degree of ionic dissociation of the polymer to quantities of water and alcohol dissolved in the polymer. From these equations, an equation for selective dissolution R is derived which does not contain an explicit term for ionic dissociation. Dissociation affects selective dissolution only by changing the degree of swelling of the polymer. Reformulating R asymptotically obtains a reciprocal relationship between permselectivity and permeability for a water‐selective membrane. Experiments to check the validity of the relationship have been carried out using chitosan membranes neutralized by several acids. The effect of degree of neutralization also has been investigated. Results can be well understood on the supposition that ionic dissociation depends upon the water/alcohol composition, the kind of acid, and the degree of neutralization. Experimental results indicate that the reciprocal relationship is maintained over an appropriate range of feed compositions which confirm the validity of the theoretical equations for the swelling equilibrium of an ionic membrane. © 1994 John Wiley & Sons, Inc.
Negative excess volume of mixing in polybutadiene/polyisoprene blends
Authors: Kawahara Seiichi , Sato Kazuo , Akiyama Saburo
Published: April 2003

The temperature dependence of specific volume was measured for miscible polybutadiene/polyisoprene blends by dilatometry. The negative excess volume of mixing below the lower critical solution temperature was studied in terms of the Flory equation‐of‐state. In order to achieve a best‐fit of the calculated excess volume to the experimental excess volume, Flory's interaction parameter X12 was estimated to be negative for the blend. Thus, a stereo structural effect for mixing would be predicted, since only van der Waals dispersion forces are expected between blend components. Considering that one way to observe the stereo‐structural effect is to study conformational changes during mixing, solid‐state proton NMR measurements were conducted. Evidence of a conformational change was obtained for the blend. The occurrence of a structural effect was also suggested. © 1994 John Wiley & Sons, Inc.
Rheology of a mixture of liquid‐crystal polymers in solution
Authors: Ambrosino S. , Sixou P.
Published: April 2003

The rheological behavior of a mixture of two liquid‐crystal polymers, hydroxypropyl cellulose and ethyl cellulose, in acetone solution is studied. The total polymer concentration in the solvent is held constant (40%) as the ratio of the two polymers is varied. The mixtures are anisotropic, isotropic, or biphasic (isotropic/anisotropic), depending on the concentration. Curves of viscosity vs shear rate for all the mixtures studied show three regions of viscosity, as described by Onogi and Asada for liquid‐crystal polymers. The viscosity as a function of the weight ratio of the two polymers at constant shear rate exhibits deviations from additivity of viscosities of the two components at all concentrations. In mixtures of two polymers in the melt, deviations are also observed; the negative ones are attributed to phase separation and the positive ones to homogenous mixing (comparison with the phase diagram). All the mixtures studied (anisotropic, isotropic, or biphasic), show ranges of shear rates where the first normal‐stress difference is negative, as is generally observed for anisotropic liquid‐crystal polymers. It is concluded that the isotropic solutions become anisotropic under shear, as they are not far from the critical concentration. © 1994 John Wiley & Sons, Inc.
A broad‐band dielectric study of poly(vinyl chloride): Effect of molar mass and processing conditions on space‐charge mechanisms
Authors: Steeman P. A. M. , Gondard C. , Scherrenberg R. L.
Published: April 2003

The dielectric properties of poly(vinyl‐chloride) (PVC) were investigated as a function of frequency and temperature. Attention was focused on the low frequency dielectric properties. Samples with different molar masses were studied. Two dipolar retardation processes were observed, one due to a local motion in the polymeric chain and the other at the glass transition. In compression‐molded samples of high molar mass an additional low‐frequency space‐charge polarization mechanism was found at high temperatures. The effect was most pronounced at the highest molar masses. The space‐charge mechanism was absent in samples of well‐kneaded material. This macroscopic polarization process in compression molded samples is probably due to discontinuities in the poorly gelified material because of a residual grain particle structure. The detected effects of air inclusions in a PVC matrix can be described by the Maxwell‐Wagner theory. The magnitude of the space‐charge mechanism is an indication of the effectiveness of the processing method used in destroying the grain structure. © 1994 John Wiley & Sons, Inc.
Gas sorption and diffusion in hydrogen‐bonded polymers. II. Polyethersulfone/polyhydroxyether blends
Authors: Reimers M. J. , Barbari T. A.
Published: April 2003

The gas sorption behavior of CO2, C2H6, and CH4, and the gas transport behavior of CO2 and CH4, were examined for polyethersulfone (PES), polyhydroxyether, and four miscible blends containing 20, 40, 60, and 80 wt % PES. The 40 wt % PES blend exhibited the lowest sorption levels and the lowest permeabilities for all of the gases. Application of the dual‐mode sorption model revealed negative deviations for the Henry's law parameter kD that were larger than those observed for blends relying on van der Waals or simple polar interactions. Also, the magnitude of the blend interaction parameter obtained from the gas sorption data and the volume of mixing were both more negative in the hydrogen‐bonded blend. Diffusion coefficients at infinite dilution and from the dual mode/partial immobilization model exhibited minima at 40 wt % PES, as did the fractional free volume, a measure of chain packing ability. © 1994 John Wiley & Sons, Inc.
Quantitative confirmation of the crystal‐amorphous interphase in semicrystalline poly(vinylidene fluoride) and poly (vinylidene fluoride)/poly (ethyl methacrylate) blends
Authors: Ando Yutaka , Hanada Tomomi , Saitoh Kumiko
Published: April 2003

Dielectric and thermal characterizations were performed for poly (vinylidene fluoride) (PVDF)/poly (ethyl methacrylate) (PEMA) blends of different composition. The characteristics of PVDF β relaxation were shown to be little affected in the semicrystalline blends with PEMA. The relaxation strength, however, depends strongly on the PEMA content and a linear relation was found between the intensity of the β relaxation and the weight fraction of the PVDF crystal‐amorphous interphase. Phase structures of the PVDF/PEMA blends are also proposed. © 1994 John Wiley & Sons, Inc.
Drying of solvent‐coated polymer films
Authors: Vrentas J. S. , Vrentas C. M.
Published: April 2003

A set of equations is developed for the description of heat and mass transfer and film shrinkage in the drying of polymer films. The utilization of jump balances in the formulation of boundary conditions at phase interfaces is illustrated, and a solution scheme is developed for solving the coupled, nonlinear equations. The proposed model will produce the size of drying over needed to reduce the solvent concentration to the desired level. © 1994 John Wiley & Sons, Inc.
Is Colonoscopy Alone Sufficient to Screen for Ulcerative Colitis‐associated Colorectal Carcinoma?
Authors: Bruewer Matthias , Krieglstein Christian F. , Utech Markus , Bode Marc , Rijcken Emile , Anthoni Christoph , Laukoetter Mike G. , Schuermann Guido , Senninger Norbert
Published: May 2003

Abstract

Patients with ulcerative colitis (UC) are at increased risk for colorectal carcinoma (CAC). Despite the fact that patients at risk are followed closely by colonoscopy to screen for dysplasia, the prevalence of CAC is still unacceptably high. The aim of this study was to evaluate the prevalence of risk factors for CAC, such as dysplasia, and to determine the relevance of colonoscopic surveillance in the group who went on to develop cancer. A series of 24 patients with UC were diagnosed with CAC. The patients’ records were analyzed retrospectively for duration of UC, prevalence of preoperative dysplasia, and other cancer risk factors (CRFs) (e.g., pancolitis, primary sclerosing cholangitis, early onset of UC, and backwash ileitis). The mean age of the patients at the time of cancer diagnosis was 43 years with an average UC duration of 15 years (6 patients had had UC less than 8 years). CAC was identified preoperatively by colonoscopy in 15 of 24 patients, with an additional 7 of 15 showing flat dysplasia. Five of nine patients without preoperatively diagnosed CAC had flat dysplasia. Overall, 19 patients had additional CRFs, most of them with at least two more CRFs. Despite a regular colonoscopic follow‐up for most patients with UC, flat dysplasia was missed in 12 patients preoperatively. Therefore we suggest that patient information should also always include surgical options in each case where significant cancer risk factors are found.
Long‐term Outcome after Inflammatory Abdominal Aortic Aneurysm Repair: Case‐matched Study
Authors: Bonati Luigi , Rubini Patrizia , Japichino Gioacchino G. , Parolari Alessandro , Contini Sandro , Zinicola Roberto , Fusari Melissa , Biglioli Paolo
Published: May 2003

Abstract

The purpose of this study was to compare early and late outcomes after inflammatory and noninflammatory abdominal aortic aneurysm (AAA) repair with emphasis on graft‐related complications. Of 625 consecutive patients submitted to AAA repair, 18 were classified as having inflammatory AAAs (group 1). The results of this group were compared with those of 54 patients (group 2) retrospectively drawn from patients who underwent aortic replacement for noninflammatory AAAs. A computer‐assisted matching system was used to match patients according to date of birth, gender, and surgical priority. All patients of both groups were followed by periodic clinical and instrumental examinations. Patients in group 1 complained more frequently of aneurysm‐related symptoms (72% vs. 20%; p = 0.0001), and their erythrocyte sedimentation rate was elevated more often (78% vs. 19%; p < 0.0001). Surgical morbidity and mortality rates were not different. The mean lengths of follow‐up were 61 ± 47 months (group 1) and 71 ± 38 months (group 2). The 10‐year overall survival rates did not differ significantly between the two groups (49.1% ± 16.9% for group 1 vs. 61.6% ± 13.8% for group 2; p = 0.26, log‐rank test). In contrast, the free from paraanastomotic aneurysm survival rates were significantly lower in group 1 (57.3% ± 20.2% vs. 97.8% ± 2.5% at 10 years; p = 0.025, log‐rank test). Long‐term outcomes showed a higher incidence of graft‐related complications in group 1. As inflammatory aneurysms might represent a risk factor for the development of paraanastomotic aneurysms, routine imaging surveillance of graft aortic healing after inflammatory AAA repair is warranted.
Optimal Lymphadenectomy for Squamous Cell Carcinoma in the Thoracic Esophagus: Comparing the Short‐ and Long‐term Outcome among the Four Types of Lymphadenectomy
Authors: Fujita Hiromasa , Sueyoshi Susumu , Tanaka Toshiaki , Fujii Teruhiko , Toh Uhi , Mine Takashi , Sasahara Hiroko , Sudo Tomoya , Matono Satoru , Yamana Hideaki , Shirouzu Kazuo
Published: May 2003

Abstract

Controversy continues over the optimal extent of lymphadenectomy (regional versus three‐field) for a potentially resectable squamous cell carcinoma in the thoracic esophagus. In the Consensus Conference of the International Society for Diseases of the Esophagus (ISDE), held in Munich in 1994, the types of lymphadenectomy were classified as standard, extended, total, or three‐field lymphadenectomy. The objective of the present study was to determine the optimal procedure among these four types of lymphadenectomy. The mortality and morbidity rates, postoperative course, and survival rates were compared among 302 patients who underwent curative (R0) transthoracic esophagectomy with one of these four types of lymphadenectomy at Kurume University Hospital, Fukuoka, Japan, from 1986 to 1998. Three‐field lymphadenectomy resulted in better survival than any other type of lymphadenectomy for patients with positive lymph node metastasis from a cancer in the upper or middle thoracic esophagus. A postoperative complication, such as recurrent laryngeal nerve paralysis, anastomotic leakage, and tracheal ischemic lesion, was significantly more common after three‐field lymphadenectomy. However, the mortality rate was the same among the four procedures. Three‐field lymphadenectomy was optimal for an upper or middle thoracic esophageal cancer with metastasis in the lymph node(s) based on improved long‐term survival, whereas there was not a large difference in short‐term and long‐term outcomes after the four types of lymphadenectomy for a lower thoracic esophageal cancer.
Spectroscopic identification of the axial ligands of cytochrome b560 in bovine heart succinate‐ubiquinone reductase
Authors: Crouse Brian R. , Yu Chang-An , Yu Linda , Johnson Michael K.
Published: May 2003

The axial ligands of low potential cytochrome b
560 in the five subunit bovine heart succinate‐ubiquinone reductase complex and in the isolated quinone binding proteins have been investigated using EPR and near‐infrared magnetic circular dichroism spectroscopies. The results are consistent with bis‐histidine ligation with near‐perpendicular imidazole rings for cytochrome b
560 in the four‐subunit complex. The pronounced changes in EPR properties that accompany isolation of the cytochrome‐b
560 containing quinone binding proteins, are attributed to perturbation of the orientation of the imidazole rings of the heme bis‐histidine ligands, rather than a change in axial ligation.
STE2/SCG1‐dependent inhibition of STE4‐induced growth arrest by mutant STE4ΔC6 in the yeast pheromone response pathway
Authors: Coria Roberto , Saviñon-Tejeda Alma L. , Birnbaumer Lutz
Published: May 2003

The yeast pheromone response pathway involves the activation of a heterotrimeric G protein composed by SCGI (α) (also GPA1), STE4 (β), and STE18 (γ) subunits by the pheromone‐activated receptors STE2 and STE3 in a and α cells, respectively. Upon exchange of bound GDP for GTP in the SCG1 subunit, the release of STE4/STE18 dimer occurs which, in turn causes activation of downstream effectors leading growth arrest and mating competence. Over‐expression of STE4 also leads to growth arrest in a STE18 dependent manner. Removal of 6 amino acids from the C‐terminus of STE4 rendered a subunit incapable of downstream signalling but still able to interact with STE18. This ΔC6 mutant acts as a dominant negative because it blocks the growth arresting effect obtained by over‐expression of STE4. The inhibitory effect of STE4ΔC6 is dependent on the presence of the SCG1 subunit in a STE2 but not ste2 background. Inhibition of the growth arresting effect of STE4 by the ΔC6 mutant is not due to competition at the effector site, but rather involves an intrinsic activity of STE2 that is dependent on SCG1.