bluuebunny/crossref_metadata_2025 huggingface dataset:
Do cocarcinogenic effects of ELF electromagnetic fields require repeated long‐term interaction with carcinogens? Characteristics of positive studies using the DMBA breast cancer model in rats
Authors: Löscher W.
Published: August 2002

The carcinogenic or cocarcinogenic potential of extremely low frequency (ELF; 50 or 60 Hz) magnetic fields (MFs) has been evaluated worldwide in diverse animal model systems. Though most results have been negative, weakly positive or equivocal results have been reported in several cancer models, including the rat DMBA (7,12‐dimethylbenz[a]anthracene) model of mammary cancer. Based on the experimental conditions used in studies in which cocarcinogenic effects of ELF MF were found, it was recently proposed that MF exposure may potentiate the effects of known carcinogens only when the animals are exposed to both MF and carcinogen during an extended period of tumor development, i.e., when the carcinogen is given repeatedly during MF exposure. This review summarizes a series of experiments from our group, showing cocarcinogenic MF effects in the DMBA breast cancer model in rats, to test whether the above proposal is confirmed by existing data. Flux densities of 50 or 100 μT significantly increased the growth of mammary tumors, independent of whether DMBA was given in a single administration or repeatedly over a prolonged period. Thus, these data do not substantiate the hypothesis requiring repeated doses of DMBA during MF exposure. Instead, several other aspects of study design and experimental factors are identified that seem to be critical for the detection of cocarcinogenic effects of MF exposure in the rat DMBA mammary cancer model. These include the rat subline used, the dose of DMBA, the duration of MF exposure, the flux density, the background (sham control) tumor incidence, and the location of mammary tumors in the mammary gland complex. These and other experimental aspects may explain why some laboratories did not detect cocarcinogenic MF effects in the DMBA model. We hope that direct comparison of MF bioeffects in different rat sublines and further evaluation of other experimental differences between studies on MF exposure in the DMBA model will eventually determine which genetic and environmental factors are critical for potential carcinogenic or cocarcinogenic effects of ELF MF exposure. Bioelectromagnetics 22:603–614, 2001. © 2001 Wiley‐Liss, Inc.
Estimating the magnitude of the sum of two magnetic fields with uncertain spatial orientations, polarizations, and/or relative phase
Authors: Kaune W.T.
Published: August 2002

A problem frequently encountered when modeling the power frequency magnetic fields, B and A, produced by two sources is the necessity of estimating the root mean square (rms) magnitude of their sum, i.e., T = |B + A|, when the rms magnitudes, B and A, of the fields are specified by the model, but not necessarily their spatial directions, polarizations, and/or relative phase. The estimator $Q=\sqrt {B^2+A^2}$ was proposed many years ago for this purpose. The accuracy of this estimator is characterized in this paper. If it is known that B and A are approximately linearly polarized and in phase, the maximum bias (i.e., systematic) and random errors for Q used to estimate T are 6.1 and 35%, respectively, when B = A. These errors decrease as the difference between B and A increases. The bias and random errors are, respectively, 3.2 and 26% when B = 2A or A/2 and 0.2 and 5.8% when B = 10A or A/10. If the directions, relative phase, and polarizations of the two fields are unknown, Q has maximum bias and random errors of ≈ 2.6 and ≈ 23%, respectively, when B = A. These errors decrease to ≈ 1.5 and ≈ 18% when B =2 A or A/2 and ≈ 0.08 and ≈ 4.0% when B = 10A or A/10. If B and A are known to be linearly polarized and collinear, but with unknown phase between them, the maximum bias and random errors are 11 and 48%, respectively, when B = A. The errors are 5.1 and 32% when B = 2A or A/2 and 0.2 and 7.0% when B = 10A or A/10. Estimators for T with zero bias can be derived, but they are more complicated and increase overall accuracy very little. Bioelectromagnetics 23:59–67, 2002. © 2002 Wiley‐Liss, Inc.
Selective activity of butyrylcholinesterase in serum by a chemiluminescent assay
Authors: Yavo Boni , Brunetti Iguatemy L. , da Fonseca Luiz M. , Catalani Luiz H. , Campa Ana
Published: August 2002

In a previous study, we showed that purified commercial esterase activity can be detected in a chemiluminescent assay based on the hydrolysis of 2‐methyl‐1‐propenylbenzoate (MPB) to 2‐methyl‐1‐propenol, which is subsequently oxidized by the horseradish peroxidase (HRP)–H2O2 system. The purpose of this study was to verify the applicability of this assay to human serum. The existence of an esterase activity capable of hydrolysing MPB is indicated by the fact that the MPB–serum–HRP–H2O2 system consumes oxygen and emits light. Both signals were abolished by prior serum heat inactivation and were preserved when serum was stored at ≤4°C. Addition of aliesterase inhibitors, such as fluoride ion and trichlorfon or the cholinesterase inhibitor eserine, totally prevents light emission. The butyrylcholinesterase‐specific substrate benzoylcholine causes a delay in both O2 uptake and light emission, while the specific acetylcholinesterase substrate, acetyl‐β‐methylcholine, had practically no effect. Purified butyrylcholinesterase, but not acetylcholinesterase, triggered light emission. The finding that butyrylcholinesterase is responsible for the hydrolysis of MPB in serum should serve as the basis for the development of a specific chemiluminescent assay for this enzyme. Copyright © 2001 John Wiley & Sons, Ltd.
Direct chemical extraction of a recombinant viral coat protein from Escherichia coli at high cell density
Authors: Choe Woo‐seok , Middelberg Anton P.J.
Published: August 2002

The release of protein and DNA from nonrecombinant E. coli JM101 and recombinant E. coli HMS174(DE3) expressing L1 (the major viral coat protein of human papillomavirus type 16) as an inclusion body was demonstrated at high cell density (OD600 = 160). For the nonrecombinant strain, extraction efficiency decreased significantly as cell mass increased, with a high viscosity increase in the postextraction broth. A different dependence on cell concentration was observed for the recombinant strain, with total protein extraction efficiency exceeding 85% for both uninduced and induced cells. Almost complete release of the recombinant L1 protein was achieved at high cell concentration (OD600 = 80 ∼ 160) without the use of reducing agent. This greatly extends the concentration range for chemical extraction. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 451–455, 2001.
Effect of operating variables on the yield of recombinant trypsinogen for a pulse‐fed dilution‐refolding reactor
Authors: Mark Buswell A. , Ebtinger Mark , Vertés Alain A. , Middelberg Anton P.J.
Published: August 2002

The inclusion body process route for manufacturing proteins offers distinct process advantages in terms of expression levels and the ease of initial inclusion body recovery. The efficiency of the refolding unit operation, however, does determine the overall economic feasibility of a process. Dilution refolding is the simplest and most extensively used refolding operation, although significant yield losses often occur due mainly to aggregation. Operating variables may have a significant effect on the degree of aggregation, but a systematic study has not been reported. This study investigates the effect of operating variables on the dilution refolding of solubilized r‐trypsinogen inclusion bodies in a pulse‐fed stirred reactor. Variables investigated were inclusion body washing, stirring speed, feed rate, concentration of solubilized r‐trypsinogen, and concentration of urea during solubilization of the inclusion bodies. Additionally, the effect of baffles in the reactor was investigated. The yield of renatured r‐trypsinogen varied between 12 ± 0.2% and 21 ± 1.0% depending on the specific combination of operating variables employed. It is clear that a suboptimal operating strategy can significantly reduce protein yield. In particular, we note that an increased intensity of mixing adversely affected yield in contrast to previous reports indicating that enhanced dispersion increases yield. We conclude that yield is determined not only by the efficiency of dispersion, but also by the local chemical environment of the protein as it folds, and the rate of change of this environment. This will be controlled by micromixing effects, and hence the intensity of agitation, in a complex manner requiring further characterization. © 2002 John Wiley & Sons, Inc. Biotechnol Bioeng 77: 435–444, 2002; DOI 10.1002/bit.10148
Strain selection of Metarrhizium anisopliae by image analysis of colony morphology for consistency of steroid biotransformation
Authors: Yang Kui , Wang Jifen , Li Xiaojing , Feng Xia , Duan Shiduo
Published: August 2002

Quantitative description of colony morphological images of the fungus Metarrhizium anisopliae was done by means of computer image analysis based on fractal analysis. Compared with simple fractal analysis, the differences in the morphological features of colonies were expressed more accurately by multifractal analysis. The use of multifractal analysis markedly improved the reliability of colony image analysis, which could be extended to morphological characterization for colony recognition and classification. First, the multifractal spectrum was calculated from each morphological image and 14 features were defined on the spectrum to describe the spectral line profile. Second, three features, α‐right, α‐width, and f‐start, were selected from the 14 features in two‐dimensional feature vector spaces and a feature augmented vector (α‐right, α‐width, and f‐start, 1)T was generated and used for classifier design. Third, a statistical least mean square error (LMSE) algorithm was applied to design a piecewise‐linear classifier, which consists of two linear classifiers, d1(x) and d2(x). Representative colony samples were used as training and test sample sets, which were previously classified into a high‐activity class and another class by a training person. After passing the training phase, the piecewise‐linear classifier could be used for automated classification of unknown colony samples. A correct recognition rate of 96% was achieved in this manner. Compared with conventional strain selection methods, this new method has the advantage of less subjectivity, reduced labor and time, and improved ability to deal with a large number of colonies. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 53–62, 2001.
Stretching the boundary: the possibilities of flexibility as an organizational capability in industrial ecology
Authors: Boons Frank , Berends Marjolein
Published: August 2002

The concept of industrial ecology focuses on groups of firms and their stakeholders that interact to achieve sustainable development. This article presents a dynamic approach to the interaction within such networks of organizations. The literature on networks and group dynamics provides us with contradicting views on the extent to which learning is possible in a developing group of organizations. We assess these views, and apply them to three types of groups of firms: sectors of industry, product chains, and regionally defined groups. In addition, the necessary capabilities of individual organizations to learn within these contexts are discussed. Copyright © 2001 John Wiley & Sons, Ltd. and ERP Environment
Beyond the business case for corporate sustainability
Authors: Dyllick Thomas , Hockerts Kai
Published: August 2002

The article is intended as a contribution to the ongoing conceptual development of corporate sustainability. At the business level sustainability is often equated with eco‐efficiency. However, such a reduction misses several important criteria that firms have to satisfy if they want to become truly sustainable.

This article discusses how the concept of sustainable development has evolved over the past three decades and particularly how it can be applied to the business level. It then goes on to describe the three types of capital relevant within the concept of corporate sustainability: economic, natural and social capital.

From this basis we shall then develop the six criteria managers aiming for corporate sustainability will have to satisfy: eco‐efficiency, socio‐efficiency, eco‐effectiveness, socio‐effectiveness, sufficiency and ecological equity. The article ends with a brief outlook towards future research. Copyright © 2002 John Wiley & Sons, Ltd. and ERP Environment
The United Nations Convention on the Rights of the Child: a basis for Jus Cogens prohibition of juvenile capital punishment in the United States*
Authors: Walker Nancy E.
Published: August 2002

This article supports the position that the 1989 United Nations Convention on the Rights of the Child (CRC) articulates a prohibition of capital punishment of juveniles that now must be considered a norm of jus cogens. The article provides statistics and trends regarding juveniles who commit capital crimes and describes how the U.S. justice system handles such juveniles, including Eighth Amendment analyses of juvenile executions under the U.S. Constitution. The article also discusses community consensus regarding evolving standards of decency, describes international law on the capital punishment of juveniles, and outlines worldwide trends in juvenile executions. It then defines and describes the concepts of customary international law and jus cogens, applying these concepts to the problem of the execution of juveniles in the United States. The article concludes by suggesting that there is a moral imperative for universal prohibition of juvenile capital punishment and by speculating about the domestic effects of applying such a jus cogens norm in the United States. Copyright © 2001 John Wiley & Sons, Ltd.
Student responses to the gross anatomy laboratory in a medical curriculum
Authors: Dinsmore Charles E. , Daugherty Steven , Zeitz Howard J.
Published: August 2002

Working with cadavers, whether through active dissection or by examination of prosected specimens, constitutes a potential stressor in medical education although there is no consensus on its effect. Some reports have suggested that it creates such a strongly negative experience that it warrants special curricular attention. To assess the issue for ourselves, we administered surveys to the freshman medical students taking the Anatomical Sciences course in the problem‐based Alternative Curriculum (A.C.) at Rush Medical College for four consecutive years. We found that although a vast majority of students expressed a positive attitude toward the experience, both before and after taking the course, there remains a small percentage of students for whom human dissection may initially be a traumatic experience. We offer explanations for our findings, comments on disparate results from other studies and suggestions for appropriate responses by anatomy faculty, who must address these student needs. Clin. Anat. 14:231–236, 2001. © 2001 Wiley‐Liss, Inc.
Key Literature
Authors: No author
Published: August 2002

This chapter provides an annotated list of literature that the authors of this issue of New Directions for Community Colleges deem key to the subjects covered in their chapters.
Percutaneous transvenous mitral commissurotomy: Immediate and long‐term follow‐up results
Authors: Arora Ramesh , Kalra Gurcharan Singh , Singh Sandeep , Mukhopadhyay Saibal , Kumar Ashish , Mohan Jagdish Chander , Nigam Madhuri
Published: August 2002

Percutaneous transvenous mitral commissurotomy has emerged as an effective nonsurgical technique for the treatment of patients with symptomatic mitral stenosis. This report highlights the immediate and long‐term follow‐up results of this procedure in an unselected cohort of patients with rheumatic mitral stenosis from a single center. It was performed in a total of 4,850 patients using double balloon in 320 (6.6%), flow‐guided Inoue balloon technique in 4,374 (90.2%), and metallic valvulotome in 156 (3.2%) patients. Their age range was 6.5–72 years (mean, 27.2 ± 11.2 years) and 1,552 (32%) patients were under 20 years of age. Atrial fibrillation was present in 702 (14.5%) patients. No patient was rejected on the basis of echocardiographic score using the Wilkins criteria. Echocardiographic score of ≥ 8 was present in 1,632 (33.6%) patients, of which 103 (2.1%) had densely calcified (Wilkins score 4+) valve. A detailed clinical and echocardiographic (two‐dimensional, continuous‐wave Doppler and color‐flow imaging) assessment was done at every 3 months for the first year and at 6‐month interval thereafter. The procedure was technically successful in 4,838 (99.8%) patients but optimal result was achieved in 4,408 (90.9%) patients with an increase in mitral valve area (MVA) from 0.7 ± 0.2 to 1.9 ± 0.3 cm2 (P < 0.001) and a reduction in mean transmitral gradient from 29.5 ± 7.0 to 5.9 ± 2.1 mm Hg (P < 0.001). The mean left atrial pressure decreased from 32.1 ± 9.8 to 13.1 ± 6.2 mm Hg (P < 0.001). Although there was no statistically significant difference in the MVA achieved between de novo and restenosed valves (1.9 ± 0.3 and 1.8 ± 0.2 cm2, respectively; P > 0.05), or between noncalcific and calcific valves (2.0 ± 0.3 and 1.8 ± 0.2 cm2, respectively; P > 0.05), on the whole MVA obtained after percutaneous transvenous mitral commissurotomy was less in restenosed and calcific valves. Ten (0.20%) patients had cardiac tamponade during the procedure. Mitral regurgitation appeared or worsened in 2,038 (42%) patients, of which 68 (1.4%) developed severe mitral regurgitation. Urgent mitral valve replacement was carried out in 52 (1.1%) of these patients. Data of 3,500 patients followed over a period of 94 ± 41 months (range, 12–166 months) revealed MVA of 1.7 ± 0.3 cm2. Elective mitral valve replacement was done in 34 (0.97%) patients. Mitral restenosis was seen in 168 (4.8%) patients, of which 133 (3.8%) were having recurrence of class III or more symptoms. Thus, percutaneous transvenous mitral commissurotomy is an effective and safe procedure with gratifying results in high percentage of patients. The benefits are sustained in a majority of these patients on long‐term follow‐up. It should be considered as the treatment of choice in patients with rheumatic mitral stenosis of all age groups. Cathet Cardiovasc Intervent 2002;55:450–456. © 2002 Wiley‐Liss, Inc.
Efficacy of heparin‐coated stent in early setting of acute myocardial infarction
Authors: Shin Eak Kyun , Son Ji Won , Sohn Min Soo , Jin Dong Kyu , Park Gi Soo , Koh Kwang Kon , Ahn Tae Hoon , Choi In Suck
Published: August 2002

Primary stenting has been reported to be superior to balloon percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) for recurrent ischemia, target lesion revascularization, and restenosis. However, concerns about early reocclusion or thrombosis after stenting in the very thrombotic environment of acute myocardial infarction still remain. Therefore, postprocedural short‐term heparin or GpIIb/IIIa receptor blockades has been used. The aim of our study was to evaluate the safety, feasibility, and long‐term efficacy of heparin‐coated stent in the early setting of AMI without postprocedural heparin or GpIIb/IIIa receptor blockade infusion. We studied 102 consecutive patients presenting to cardiac catheterization laboratory ≤ 6 hr from the onset of chest pain. No patients who were implanted with heparin‐coated stents received heparin or GpIIb/IIIa receptor blockade infusion after the procedures, not even patients who showed an angiographically large thrombus burden before stenting. Patients were evaluated for clinical endpoints at 30 days and 6 months. Coronary angiography was required for all patients at 2 weeks and 6 months after the procedure. Angiographic and procedural successes were 100% and 98%, respectively. Two patients (2%) died of heart failure without evidence of reocclusion of stented vessel during the hospitalization and 4 (4%) additional patients died of refractory heart failure within the first 6 months. Major bleeding complication occurred in one patient (1%). Recurrent myocardial infarction developed in one patient at 4 months. Early angiographic follow up at 2 weeks was performed in 88% of all patients, none of whom showed thrombotic stent occlusion. Six‐month angiographic follow‐up was completed in 71%(64/91) of eligible patients and binary restenosis was present in 17.2% of stented vessels. Eight(8%) patients underwent repeat PTCA. Cardiac event‐free survival rate at 6 months was 86.3%. This study demonstrates that heparin‐coated stents are safe in the early setting of acute myocardial infarction and no additional heparin infusion after stenting is necessary, which may reduce bleeding complications. Angiographic restenosis rate compares favorably to the binary restenosis rate from other studies with uncoated stents. Cathet Cardiovasc Intervent 2001;52:306–312. © 2001 Wiley‐Liss, Inc.
Gadolinium‐based coronarography in a patient with renal failure: First clinical report
Authors: Sarkis Antoine , Badaoui Georges , Slaba Samy , Moussalli Aida , Jebara Victor A.
Published: August 2002

This article reports the use of gadolinium to perform a coronarography in a patient with renal insufficiency, unstable angina, and peripheral vascular disease. The examination was well tolerated and the images obtained of good quality. Cathet Cardiovasc Intervent 2001;54:68–69. © 2001 Wiley‐Liss, Inc.
Prediction intervals in linear regression taking into account errors on both axes
Authors: del Río F. Javier , Riu Jordi , Rius F. Xavier
Published: August 2002

This study reports the expressions for the variances in the prediction of the response and predictor variables calculated with the bivariate least squares (BLS) regression technique. This technique takes into account the errors on both axes. Our results are compared with those of a simulation process based on six different real data sets. The mean error in the results from the new expressions is between 4% and 5%. With weighted least squares, ordinary least squares, the constant variance ratio approach and orthogonal regression, on the other hand, mean errors can be as high as 85%, 277%, 637% and 1697% respectively. An important property of the prediction intervals calculated with BLS is that the results are not affected when the axes are switched. Copyright © 2001 John Wiley & Sons, Ltd.
Chiral recognition of binaphthyl derivatives: A chiral recognition model on the basis of chromatography, spectroscopy, and molecular mechanistic calculations for the enantioseparation of 1,1′‐binaphthyl derivatives on cholic acid‐bonded stationary phases
Authors: Vaton‐Chanvrier L. , Oulyadi H. , Combret Y. , Coquerel G. , Combret J.C.
Published: August 2002

In an effort to elucidate the mechanism of chiral discrimination of cholic acid‐based stationary phases, the enantiomeric recognition ability of six chiral stationary phases (CSPs), prepared from differently substituted cholic acid derivatives, was evaluated in normal phase high‐performance liquid chromatography (HPLC) with a series of 1,1′‐binaphthyl compounds. The influence of structural variations of analytes on retention and enantioselectivity was investigated. Particularly high values of enantioselectivity were observed for the binaphthol enantiomers on a CSP prepared from the allyl 7α,12α‐dihydroxy‐3α‐phenylcarbamoyloxy‐5β‐cholan‐24‐oate. The complexes of this chiral selector with both enantiomers of binaphthol were studied as models for the interactions responsible for the enantioseparation with the cholic acid‐based stationary phases. The 1:1 stoichiometry of the complex in solution was determined by UV titration. The chiral selector dissolved in chloroform exhibited a chiral discrimination for the binaphthol in 1H and 13C nuclear magnetic resonance (NMR) spectroscopies. Some aromatic proton and carbon resonances of binaphthol were clearly separated into a pair of peaks due to enantiomers in the presence of the chiral selector. Moreover, on the basis of molecular mechanics calculation, a chiral discrimination model was proposed which nicely explains the relevant chromatographic behavior of the 1,1′‐binaphthyl derivatives. Chirality 13:668–674, 2001. © 2001 Wiley‐Liss, Inc.
Chiral discrimination by HPLC and CE and antifungal activity of racemic fenticonazole and its enantiomers
Authors: Quaglia M.G. , Donati E. , Desideri N. , Fanali S. , D'auria F.D. , Tecca M.
Published: August 2002

Fenticonazole is a chiral antifungal agent, used in therapy as the racemic mixture. The investigation on the chirality of fenticonazole is reported in this study. rac‐Fenticonazole was resolved by HPLC and by capillary electrophoresis (CE). The chiral stationary phase (CSP), used in HPLC, was Daicel OD‐H, a commercial phase, which allowed the separate collection of the two enantiomers. The chiral selectors used for CE were some cyclodextrin derivatives. The analysis time required from CE was about the half the HPLC enantioseparation time. The biological activity of the rac‐mixture and each individual enantiomer was tested against Cryptococcus neoformans and two Aspergillus nidulans strains. The minimum inhibitory concentration (MIC) evaluation showed that the eutomer was the enantiomer chromatographically more retained and had a longer migration time in the electrophoretic enantioseparation. The CD spectrum of the eutomer showed a positive Cotton effect. Chirality 14:449–454, 2002. © 2002 Wiley‐Liss, Inc.
Chiral separation of pheniramine‐like 3‐phenyl‐3‐heteroarylpropylamines by CE and HPLC methods
Authors: Schuster Andreas , Götte Carsten , Bernhardt Günther , Buschauer Armin
Published: August 2002

Analytical CE and HPLC methods were developed for the chiral separation of halogen‐substituted 3‐phenyl‐3‐(2‐pyridyl)propylamines 1–4 (1: 3‐(4‐fluorophenyl)∼, 2: 3‐(3,4‐difluorophenyl)∼, 3: 3‐(4‐chlorophenyl)∼, 4: 3‐(3,4‐dichlorophenyl)∼), 3‐(4‐fluorophenyl)‐3‐(2‐thiazolyl)propylamine (5), and 3‐(4‐fluorophenyl)‐3‐(1‐benzylimidazol‐2‐yl)propylamine (6), which are building blocks for the preparation of very potent arpromidine‐type histamine H2 receptor agonists. All amines were enantioseparated by CE with resolutions of at least 1.8 using α‐, β‐, or γ‐cyclodextrin (CD) as chiral selectors. With heparin as buffer additive for CE the optical antipodes of 1–4 and 6 were separated with resolutions ≥1.8. On RP‐18 columns the separation of the (+)‐(S)‐acetylmandelic acid amides of racemic 2 (R = 0.9, α = 1.07) and the thioureas prepared by addition of 6 to 2,3,4,6‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl isothiocyanate (R = 2.0, α = 1.20) was successful, whereas the diastereomeric ureas prepared from 3 and (+)‐(S)‐1‐(1‐naphthyl)ethyl isocyanate could not be resolved. Separation of the diastereomeric isoindoles prepared from 1–5, o‐phthaldialdehyde and 2,3,4,6‐tetra‐O‐acetyl‐1‐thio‐β‐D‐glucopyranoside was achieved on a RP‐18 phase (R ≥ 0.4, a ≥ 1.02). Direct separation of the enantiomers of 3 and 4 was achieved on a Cyclobond I column (R ≥ 0.9, α ≥ 1.07). α‐ and β‐CD were also useful as mobile phase additives for HPLC (3 and 4: RP‐18 column, β‐CD, R ≥ 0.4, α ≥ 1.03; 3: RP‐18 column, α‐CD: R = 0.5, α = 1.04). Chirality 13:285–293, 2001. © 2001 Wiley‐Liss, Inc.
Steady‐state pharmacokinetics of indobufen enantiomers in patients with obliterative atherosclerosis
Authors: Główka F.K. , Strzelecka D. , Zapalski S.
Published: August 2002

Steady‐state pharmacokinetics of indobufen (INDB) enantiomers administered as racemic INDB (rac‐INDB) tablets and bleeding time were studied in patients. Two‐hundred mg INDB tablets (Ibustrin) were administered twice daily for 7 days to obliterative atherosclerosis patients. Enantiospecific reversed phase (RP) HPLC with UV detection (λ = 275 nm) was used for determination of INDB enantiomers in serum of patients. The ratio AUCR:AUCS equalled 1.7 ± 0.2 as a result of higher (−)‐R‐enantiomer serum levels. The (+)‐S‐enantiomer was more rapidly eliminated (oral clearance, Cl = 1.1 ± 0.3 L/h) than its (−)‐R‐antipode (Cl = 0.7 ± 0.2 L/h). Therefore, the mean steady/state levels of (−)/R/enantiomer (13.5 ± 3.8 mg/L) exceeded those of its (+)‐S‐enantiomer (7.8 ± 1.8 mg/L). Furthermore, half‐life (t1/2) was significantly shorter for (+)‐S‐INDB (t1/2 = 4.5 ± 1.2 h as compared to (−)‐R‐INDB (t1/2 = 7.4 ± 2.4 h). However, no significant differences were observed in the respective Vd values. The bleeding time of patients was not significantly extended. The above pharmacokinetic data provide a rationale for potential future replacement of INDB racemic tablets with tablets of its (+)‐S‐enantiomer. Chirality 13:308–312, 2001. © 2001 Wiley‐Liss, Inc.
Light chains of mammalian cytoplasmic dynein: identification and characterization of a family of LC8 light chains
Authors: Wilson Matthew J. , Salata Mark W. , Susalka Stephen J. , Pfister K. Kevin
Published: August 2002

Cytoplasmic dynein is a large multisubunit motor protein that moves various cargoes toward the minus ends of microtubules. In addition to the previously identified heavy, intermediate, and light intermediate chains, it has recently been recognized that cytoplasmic dynein also has several light chain subunits with apparent molecular weights between 8–20 kDa. To systematically identify the light chains of purified rat brain cytoplasmic dynein, peptide sequences were obtained from each light chain band resolved by gel electrophoresis. Both members of the tctex1 light chain family, tctex1 and rp3, were identified in a single band. Only one member of the roadblock family, roadblock‐2, was found. Two members of the LC8 family were resolved as separate bands, the previously identified LC8 subunit, and a second novel cytoplasmic dynein family member, LC8b. The tissue distribution of these two dynein LC8 subunits differed, although LC8b was the major family member in brain. Database searches found that both LC8a and LC8b were also present in several mammalian species, and a third mammalian LC8 sequence, LC8c was found in the human database. The amino acid sequences of both LC8a and LC8b were completely conserved in mammals. LC8a and LC8b differ in only six of the 89 amino acids. The amino acid differences between LC8a and LC8b were located near the N‐terminus of the molecules, and most were in the outward facing α‐helices of the LC8 dimer. When the mammalian LC8a sequence was compared to the LC8 sequences found in six other animal species including Xenopus and Drosophila, there was, on average, 94% sequence identity. More variation was found in LC8 sequences obtained from plants, fungi, and parasites. LC8c differed from the other two human LC8 sequences in that it has amino acid substitutions in the intermediate chain binding domain at the C‐terminal of the molecule. The position of amino acid substitutions of the three mammalian LC8 family members is consistent with the hypothesis that they bind to different proteins. Cell Motil. Cytoskeleton 49:229–240, 2001. © 2001 Wiley‐Liss, Inc.
Finite‐difference time‐domain‐based studies of MRI pulsed field gradient‐induced eddy currents inside the human body
Authors: Liu Feng , Crozier Stuart , Zhao Huawei , Lawrence Ben
Published: August 2002

In modern magnetic resonance imaging (MRI), patients are exposed to strong, rapidly switching magnetic gradient fields that, in extreme cases, may be able to elicit nerve stimulation. This paper presents theoretical investigations into the spatial distribution of induced current inside human tissues caused by pulsed z‐gradient fields. A variety of gradient waveforms have been studied. The simulations are based on a new, high‐definition, finite‐difference time‐domain method and a realistic inhomogeneous 10‐mm resolution human body model with appropriate tissue parameters. It was found that the eddy current densities are affected not only by the pulse sequences but by many parameters such as the position of the body inside the gradient set, the local biological material properties and the geometry of the body. The discussion contains a comparison of these results with previous results found in the literature. This study and the new methods presented herein will help to further investigate the biological effects caused by the switched gradient fields in a MRI scan. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 26–36, 2002.
A detunable elliptic transmission line resonator for body imaging at 3 Tesla
Authors: Ledden Patrick J. , Wald Lawrence L. , Hinton Denise P.
Published: August 2002

In this work, we demonstrate and characterize a large‐volume radiofrequency (RF) coil insert used to perform human torso magnetic resonance imaging at 3 T. The coil is a transmission line resonator of elliptic cross‐section that can be actively detuned for operation with localized receive‐only surface coils. The coil fits within the 55 cm inner bore liner of a 3 T whole body imager and accommodates small‐ to medium‐sized torsos. Sixteen flat transmission line elements are used; each is 32 cm in length and composed of multiple microstrip capacitors spaced equally inside the elliptic shield (52 cm and 40 cm major and minor axes, respectively). A four‐port electrical drive was used to improve B1 homogeneity and power efficiency. The power required for a 90° 2 ms single side‐lobe sinc pulse for the chest loaded coil was less than 2 kW. Active detuning for operation with receive‐only surface coils was achieved by placement of a low‐voltage PIN diode network on each individual transmission line element. A quadrature pair of 10 × 15 cm2 rectangular surface coils with active detuning traps was used for high spatial resolution cardiac and spine imaging. Since the coil is completely portable, any anatomical region of interest may be centered within the active volume. The head loaded coil required less power and enabled the use of standard 180° pulses well within specific absorption rate limits. Occipital lobe images using a receive‐only quadrature 8 cm loop surface coil pair are also presented. As the number of high‐field whole body systems increases, an RF coil insert optimized for the torso provides an economical and efficient strategy for extending the capabilities of these systems beyond neuroimaging. © 2002 Wiley Periodicals, Inc. Concepts in Magnetic Resonance (Magn Reson Engineering) 15: 92–100, 2002.
Histopathologic grading of medulloblastomas
Authors: Eberhart Charles G. , Kepner James L. , Goldthwaite Patricia T. , Kun Larry E. , Duffner Patricia K. , Friedman Henry S. , Strother Douglas R. , Burger Peter C.
Published: August 2002

BACKGROUND

Medulloblastomas are small cell embryonal tumors of the cerebellum found predominantly in children, only slightly more than half of whom survive. Predicting favorable outcome has been difficult, and improved stratification clearly is required to avoid both undertreatment and overtreatment. Patients currently are staged clinically, but no pathologic staging system is in use. Two rare subtypes at extreme ends of the histologic spectrum, i.e., medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas, are associated with better and worse clinical outcomes, respectively. However, there is little data about correlations between histologic features and clinical outcome for most patients with medulloblastomas that fall between these histologic extremes of nodularity and anaplasia. Therefore, the authors evaluated the clinical effects of increasing anaplasia and nodularity in a large group of children with medulloblastomas, hypothesizing that increasing nodularity would predict better clinical outcomes and that increasing anaplasia would presage less favorable results.

METHODS

Medulloblastomas from 330 Pediatric Oncology Group patients were evaluated histologically with respect to extent of nodularity, presence of desmoplasia, grade of anaplasia, and extent of anaplasia. Pathologic and clinical data were then compared using Kaplan–Meier and log‐rank analyses.

RESULTS

Increasing grade of anaplasia and extent of anaplasia were associated strongly with progressively worse clinical outcomes (P < 0.0001 for both). Significant anaplasia (moderate or severe) was identified in 24% of medulloblastoma specimens. Neither increasing degrees of nodularity nor desmoplasia were associated significantly with longer survival.

CONCLUSIONS

Moderate anaplasia and severe anaplasia were associated with aggressive clinical behavior in patients with medulloblastomas and were detected in a significant number of specimens (24%). Pathologic grading of medulloblastomas with respect to anaplasia may be of clinical utility. Cancer 2002;94:552–60. © 2002 American Cancer Society.
Prognostic value of p53 mutations, bax, and spontaneous apoptosis in maxillary sinus squamous cell carcinoma
Authors: Bandoh Nobuyuki , Hayashi Tatsuya , Kishibe Kan , Takahara Miki , Imada Masanobu , Nonaka Satoshi , Harabuchi Yasuaki
Published: August 2002

BACKGROUND

Many researchers have attempted to correlate p53 mutation and spontaneous apoptosis with the effectiveness of radiochemotherapy and with prognosis in several malignancies.

METHODS

The current study group consisted of 70 Japanese patients with maxillary sinus squamous cell carcinoma (SCC). Fifty seven patients were treated with radiochemotherapy followed by total or partial maxillectomy, and the remaining13 patients were treated with radiotherapy alone. Tumor biopsy specimens at pretreatment status were examined for apoptosis‐related proteins such as p53 protein, Fas, bax, bcl‐x, and apoptosis using immunohistologic methods. The proportion of apoptotic cells labeled by single stranded DNA antibody was expressed as an apoptotic index (AI). p53 mutations at exons 5 through 8 were analyzed by direct sequence on polymerase chain reaction amplified products obtained from laser microdissected tissues. The effectiveness of radiochemotherapy was investigated histologically on surgically dissected specimens.

RESULTS

p53 mutations were identified in 20 (29%) of 70 patients. p53 protein was overexpressed in 39 patients (56%), Fas in 20 patients (29%), bax in 40 patients (57%), and bcl‐x in 33 patients (47%). Overexpression of bax was associated with negativity of bcl‐x (P = 0.015) and with high AI (P = 0.024). Low AI and/or p53 mutation in the pretreatment tissues correlated with low histologic effectiveness of radiochemotherapy (P = 0.048, P = 0.019, respectively). Kaplan‐Meier analysis as well as univariate analysis using the Cox proportional hazards model showed that low histologic effectiveness of radiochemotherapy (P = 0.0281, P = 0.0284, respectively), p53 mutations (P = 0.0095, P = 0.0187, respectively), negativity of bax (P = 0.0069, P = 0.0191, respectively), and low AI (P = 0.0134, P = 0.0407, respectively) were significantly related to worse disease‐free survival. Multivariate analysis showed AI as an independent factor predicting for disease‐free survival (P = 0.0455).

CONCLUSIONS

The p53 mutations, expression of bax, and levels of spontaneous apoptosis have prognostic value in maxillary sinus SCC; AI especially is an independent factor for disease‐free survival. A high level of spontaneous apoptosis induced by overexpression of bax may increase sensitivity of radiochemotherapy resulting in good prognosis, while p53 mutation may lead to resistance against radiochemotherapy. resulting in poor prognosis. Cancer 2002;94:1968–80. © 2002 American Cancer Society.

DOI 10.1002/cncr.10388
The panorama of opioid‐related cognitive dysfunction in patients with cancer
Authors: Lawlor Peter G.
Published: August 2002

BACKGROUND

Opioids have an essential role in the management of pain in cancer patients, particularly those with advanced disease. Cognitive dysfunction is a recognized complication of opioid use. However, misconceptions and controversy surround the nature and prevalence of its occurrence. A projected increase in the aging cancer population highlights the need for a better understanding of this phenomenon.

METHODS

A critical appraisal of the literature evidence in relation to the pattern, pathophysiology, assessment, impact, and management of cognitive dysfunction due to opioid use in cancer pain management is given.

RESULTS

Studies in cancer patients with less advanced disease reveal subtle evidence of cognitive impairment, largely related to initial dosing or dose increases. In advanced cancer, opioid‐induced cognitive dysfunction usually occurs in the form of delirium, a multifactorial syndrome. The presence of both cognitive impairment and delirium frequently is misdiagnosed or missed. Potential risk factors include neuropathic and incidental pain, opioid tolerance, somatization of psychologic distress, and a history of drug or alcohol abuse. Elevation of opioid metabolites with renal impairment may contribute to cognitive dysfunction. Recognition of opioid‐related cognitive dysfunction is improved by objective screening. Successful management requires either dose reduction or a change of opioid, in addition to addressing other reversible precipitants such as dehydration or volume depletion.

CONCLUSIONS

Opioid‐related cognitive dysfunction tends to be subtle in the earlier stages of cancer, whereas delirium, a more florid form with behavioral disturbance is likely to be present in the advanced cancer population. In patients with advanced disease, an optimal management approach requires careful clinical assessment, identification of risk factors, objective monitoring of cognition, maintenance of adequate hydration, and either dose reduction or switching to a different opioid. Cancer 2002;94:1836–53. © 2002 American Cancer Society.

DOI 10.1002/cncr.10389
The PedsQL™ in pediatric cancer
Authors: Varni James W. , Burwinkle Tasha M. , Katz Ernest R. , Meeske Kathy , Dickinson Paige
Published: August 2002

BACKGROUND

The Pediatric Quality of Life Inventory (PedsQL) is a modular instrument designed to measure health‐related quality of life (HRQOL) in children and adolescents ages 2–18 years. The PedsQL 4.0 Generic Core Scales are multidimensional child self‐report and parent proxy‐report scales developed as the generic core measure to be integrated with the PedsQL disease specific modules. The PedsQL Multidimensional Fatigue Scale was designed to measure fatigue in pediatric patients. The PedsQL 3.0 Cancer Module was designed to measure pediatric cancer specific HRQOL.

METHODS

The PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module were administered to 339 families (220 child self‐reports; 337 parent proxy‐reports).

RESULTS

Internal consistency reliability for the PedsQL Generic Core Total Scale Score (α = 0.88 child, 0.93 parent report), Multidimensional Fatigue Total Scale Score (α = 0.89 child, 0.92 parent report) and most Cancer Module Scales (average α = 0.72 child, 0.87 parent report) demonstrated reliability acceptable for group comparisons. Validity was demonstrated using the known‐groups method. The PedsQL distinguished between healthy children and children with cancer as a group, and among children on‐treatment versus off‐treatment. The validity of the PedsQL Multidimensional Fatigue Scale was further demonstrated through hypothesized intercorrelations with dimensions of generic and cancer specific HRQOL.

CONCLUSIONS

The results demonstrate the reliability and validity of the PedsQL Generic Core Scales, Multidimensional Fatigue Scale, and Cancer Module in pediatric cancer. The PedsQL may be utilized as an outcome measure in clinical trials, research, and clinical practice. Cancer 2002;94:2090–106. © 2002 American Cancer Society.

DOI 10.1002/cncr.10427
Prognostic relevance of cell biologic and biochemical features in conventional chondrosarcomas
Authors: Aigner Thomas , Müller Susanna , Neureiter Daniel , Illstrup Duane M. , Kirchner Thomas , Björnsson Johannes
Published: August 2002

BACKGROUND

Conventional chondrosarcoma is the second most common malignant solid tumor of bone, and its management still poses a challenge for the orthopedic surgeon. Currently, tumor grade is the only parameter of prognostic significance besides stage and, possibly, resection margins. Additional independent prognostic markers therefore would be highly valuable for patient management.

METHODS

In the current study, the authors evaluated biologic markers for various chondrocytic phenotypes by histochemical and immunohistochemical technology in a large series of clinically well defined cases of enchondromas and conventional chondrosarcomas, each with at least 5 years of clinical follow‐up.

RESULTS

The authors' results confirm the strong correlation between clinical behavior and cell differentiation as expressed by marker genes. The phenotypes of the tumor cells are the biologic substrate of the histopathologic appearance of the neoplasms and, thus, the biologic basis for classic tumor grading. Collagen Types II and X, as well as the proteoglycan aggrecan, suggest a mature neoplastic phenotype and good prognosis, i.e., low recurrence rate, rare metastasis, and long survival. Conversely, collagen Type I, together with cell spindling, indicates a transition to a more proliferative, so‐called “dedifferentiated” phenotype, which clearly is associated with a poorer prognosis. The changes in cellular phenotypes are accompanied by changes in proliferative activity. Thus, low‐grade neoplasms showing mainly mature and terminally differentiated (hypertrophic) chondrocytes display only scant proliferation whereas less differentiated chondrosarcomas with biologically dedifferentiated chondrocytes show significantly higher proliferative activity, a feature that is also highly correlated with prognosis.

CONCLUSIONS

These data indicate that molecular markers are to a large extent the biologic basis of the conventional grading, rather than representing independent prognostic markers. The authors' results further indicate that COL1 has significant value in the distinction between enchondromas and low‐grade chondrosarcomas including these that are histologically similar. Further understanding of chondrocytic phenotypes will be a promising way to provide new tumor markers for better understanding, diagnosis, and treatment of chondroid neoplasms. Cancer 2002;94:2273–81. © 2002 American Cancer Society.

DOI 10.1002/cncr.10461
Depression and functional status as predictors of death among cancer patients
Authors: Stommel Manfred , Given Barbara A. , Given Charles W.
Published: August 2002

BACKGROUND

The current study examined the extent to which depression and functional limitations contribute to the mortality of newly diagnosed cancer patients. The analysis focused on differences in survival times among cancer patients with new experiences of depressive symptoms and functional limitations and patients with a history of such limitations.

METHODS

Data for the current analysis came from two panel studies conducted in Michigan between 1993 and 1997, including 871 adult (≥ 21 years of age) breast, colon, lung, and prostate carcinoma patients. Information came from four separate sources: the intake patient interview, a self‐administered questionnaire, medical record audits, and the Death Certificate Registry of Michigan's Department of Community Health. With time to death as the primary outcome (followup of 571 days), data were analyzed using Kaplan‐Meier product limit estimates and the Cox proportional hazard model.

RESULTS

Cancer patients who, after diagnosis, report only new depressive symptoms or functional limitations, have the same survival chances as those who report none. Cancer patients with either previous emotional problems or previous physical limitations face, within the first 19 months after diagnosis, a 2.6 times greater hazard of dying than patients without prior problems. Patients with both previous emotional problems and physical limitations before diagnosis have a 7.6 times greater hazard of dying within that time frame.

CONCLUSIONS

The current data show cancer patients with prior limitations and emotional problems have worse survival chances than would be expected on the basis of their cancer diagnosis alone. While depressive symptoms and functional limitations are common short‐run responses to a cancer diagnosis and initial treatment, patients with no prior history of such problems appear to be more resilient. Cancer 2002;94:2719–27. © 2002 American Cancer Society.

DOI 10.1002/cncr.10533