bluuebunny/crossref_metadata_2025 huggingface dataset:
The chemopreventive agent α‐difluoromethylornithine blocks Ki‐ras–dependent tumor formation and specific gene expression in Caco‐2 cells
Authors: Ignatenko Natalia A. , Zhang Hui , Watts George S. , Skovan Bethany A. , Stringer David E. , Gerner Eugene W.
Published: March 2004

Mutation of the Kirsten‐ras (Ki‐ras) proto‐oncogene occurs frequently in colorectal cancers. α‐Difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme, ornithine decarboxylase (ODC), inhibits Ki‐ras transformation and colon tumorigenesis in carcinogen‐treated animal models by mechanisms yet to be elucidated. Caco‐2 cells transfected with an activated Ki‐ras, but not parental cells, formed tumors in severe combined immunodeficient (SCID) mice. DFMO treatment (2% in drinking water) prevented tumor growth. Gene expression profiling was performed to identify Ki‐ras–and DFMO‐dependent patterns of gene expression. Microarray results were validated with real‐time or semi‐quantitative RT‐PCR and/or Western blot analysis. Genes upregulated in Caco‐2 cells expressing an activated Ki‐ras encoded cytoskeletal‐, transport‐, protease‐, and gap junction–associated proteins. These genes are important for normal development and maintenance of colonic epithelial tissue. Caco‐2 cells transfected with an activated Ki‐ras displayed increased expression of the integrin alpha 1 (INGA1) and enhanced cell migration on laminin. These parameters were unaffected by DFMO, but Ki‐ras–dependent migration was inhibited by INGA1 antibodies. Other Ki‐ras–dependent, but DFMO‐independent, genes included transglutaminase (TGase) and kallikrein 6 (KLK6). Ki‐ras–transfected cells also expressed increased levels of connexin43 (Cx43) (RNA and protein), tight junction protein, and endothelin 1. DFMO reversed these increases. The results indicated that the Ki‐ras oncogene caused changes in experimental cell migration and cell‐cell communication genes and that some of these changes could be reversed by DFMO. © 2004 Wiley‐Liss, Inc.
Alterations of the M6p/Igf2 receptor gene in hepatocellular carcinomas induced by N‐nitrosodiethylamine and a choline‐deficient L‐amino acid–defined diet in rats
Authors: Tsujiuchi Toshifumi , Sasaki Yasutaka , Oka Yasuo , Kuniyasu Hiroki , Konishi Yoichi , Tsutsumi Masahiro
Published: March 2004

To elucidate whether the M6p/Igf2 receptor (M6p/Igf2r) gene might be involved in exogenous and endogenous liver carcinogenesis, we investigated its alteration in hepatocellular carcinomas (HCCs) induced by N‐nitrosodiethylamine (DEN) and by a choline‐deficient L‐amino acid‐defined (CDAA) diet in rats. Male F344 rats, 6 wk old, received a single intraperitoneal (i.p.) injection of DEN at a dose of 10 mg/kg body weight, followed by combined treatment with partial hepatectomy and colchicine to induce cell cycle disturbance, and a selection procedure regimen, HCCs being obtained after 42 wk. With continuous CDAA diet feeding, tumors were sampled after 75 wk. Total RNA was extracted from individual HCCs for assessment of mutations within exons 27, 28, 31, 33, and 34, and aberrant transcript of the M6p/Igf2r gene by reverse transcription (RT)‐polymerase chain reaction (PCR)‐single strand conformation polymorphism (SSCP) and RT‐PCR analyses, respectively. Mutations were detected in three of 15 HCCs (20%) induced by the CDAA diet, a TTT to TTG (Phe to Leu) transversion at codon 1516 and two AAG to AGG (Lys to Arg) transitions at codon 1620, but in none of those caused by DEN. Aberrant transcripts were found in seven of 15 HCCs after DEN treatment (46.7%) and in two of 15 HCCs induced by the CDAA diet (13.3%). These results suggest that alterations of the M6p/Igf2r gene may be involved in both exogenous and endogenous liver carcinogenesis with the different patterns and frequencies. © 2004 Wiley‐Liss, Inc.
Screen for expanded FMR1 alleles in patients with essential tremor
Authors: Garcia Arocena Dolores , Louis Elan D. , Tassone Flora , Gilliam T. Conrad , Ottman Ruth , Jacquemont Sébastien , Hagerman Paul J.
Published: March 2004

Fragile X‐associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder, was described recently among male carriers of expanded alleles (55–200 CGG repeats; premutation range) of the fragile X mental retardation 1 (FMR1) gene. Major features of the syndrome include intention tremor, gait ataxia, and parkinsonism in men over 50 years of age. This disorder is believed to be relatively common, possibly affecting 1 in 3,000 men over the age of 50 years in the general population. This raises the possibility that some patients presenting with essential tremor (ET) may harbor expanded FMR1 alleles. We screened 81 ET patients (40 males, 41 females) for expanded FMR1 alleles to determine whether ET is associated with such alleles. None of the ET cases had the premutation genotype. CGG repeat sizes ranged from 5 to 47 repeats within this study population, suggesting that expanded FMR1 alleles are uncommon among patients with ET. Screening of movement disorder patients with other clinical features of FXTAS (e.g., ataxia and parkinsonism) may be more likely to yield expanded FMR1 alleles. © 2004 Movement Disorder Society
Clinical characteristics of Parkinson's disease among Inuit in Greenland and inhabitants of the Faroe Islands and Als (Denmark)
Authors: Wermuth Lene , Bünger Nick , Von Weitzel‐Mudersback Paul , Pakkenberg Henning , Jeune Bernard
Published: March 2004

In earlier studies, we found high age‐adjusted prevalences of Parkinson's disease (PD) in the Faroe Islands (209 per 100,000 inhabitants) and in Greenland (187.5 per 100,000 inhabitants) compared to the age‐adjusted prevalence on the island of Als in the southern part of Denmark (98.3 per 100,000 inhabitants). We thoroughly examined patients with suspected parkinsonism using internationally accepted diagnostic criteria. In the present study, we found no significant clinical differences between patients with PD in the three areas, despite this high difference in prevalence. However, comparing the age at examination and age at treatment, the patients were younger in Greenland, a higher proportion of patients had cognitive decline, and they had a higher mean Hoehn and Yahr rating score, although they received a lower levodopa dose. A higher proportion of the patients in Greenland were newly diagnosed than in the other two areas. © 2004 Movement Disorder Society
Observations on the human rejection behaviour syndrome: Denny–Brown revisited
Authors: Warren Jason D. , Hu Michele T.M. , Galloway Malcolm , Greenwood Richard J. , Rossor Martin N.
Published: March 2004

The parietal avoiding–rejection behaviour syndrome, first described by Denny‐Brown in the rhesus monkey, has been reported only rarely in humans. Here, we describe a patient with rejection behaviour in the setting of progressive cognitive decline accompanied by cortical myoclonus. © 2004 Movement Disorder Society
Ninhydrin sweat test: A simple method for detecting antibodies neutralizing botulinum toxin type A
Authors: Voller Bernhard , Moraru Ekaterina , Auff Eduard , Benesch Michael , Poewe Werner , Wissel Jörg , Müller Jörg , Entner Tanja , Bigalke Hans , Schnider Peter
Published: March 2004

Approximately 5% of patients with cervical dystonia receiving repeated botulinum neurotoxin A (BoNT/A) injections develop secondary loss of treatment benefit. Currently available tests to directly detect neutralizing BoNT/A antibodies (BoNT/A‐AB) are either expensive or time consuming. To establish a simple, clinically useful test for antibody detection, we adapted the ninhydrin sweat test (NST). Eighteen dystonic patients with secondary nonresponse and clinically suspected BoNT/A‐AB formation were tested for BoNT/A‐AB in the mouse diaphragm test (MDT). In addition, the size of the anhidrotic area was determined by the NST 21 days after an intradermal dose of 10 U Dysport into the hypothenar region of the left palm. In nine patients, positive BoNT‐AB titers were found in the MDT. There was a significant correlation between the BoNT/A‐AB titers and the anhidrotic area (Spearman's rho = −0.9, P < 0.0001). Both tests provided comparably good results with respect to qualitative antibody detection. In the clinical situation of secondary nonresponse to BoNT/A therapy, the economical NST may be a helpful tool to detect neutralizing BoNT/A‐AB. © 2004 Movement Disorder Society
Vascular hemichorea/hemiballism and topiramate
Authors: Gatto Emilia Mabel , Uribe Roca Claudia , Raina Gabriela , Gorja Marcelo , Folgar Silvia , Micheli Federico E.
Published: March 2004

Although vascular hemichorea/hemiballism (HC/HB) has been reported to be self‐limited, in some cases, it can be irreversible and severely disabling. The standard treatment includes typical and atypical neuroleptics and GABA‐mimetic drugs. Topiramate is a new antiepileptic drug possessing a complex mechanism of action, including the enhancement of GABA‐mediated inhibition. We describe a 71‐year‐old patient with HC/HB who markedly improved after topiramate treatment. © 2004 Movement Disorder Society
Solid‐phase synthesis and 1H and 13C high‐resolution magic angle spinning NMR of 13C‐labeled resin‐bound saccharides
Authors: Loening Nikolaus M. , Kanemitsu Takuya , Seeberger Peter H. , Griffin Robert G.
Published: March 2004

We show how high‐resolution magic angle‐spinning NMR spectroscopy can be used to characterize 13C‐labeled saccharides that have been prepared using solid‐phase synthesis techniques while they are still bound to a solid‐support resin. With the use of 13C‐labeled glucose as the starting material, we have successfully synthesized mono‐, di‐ and trisaccharides with uniform 13C labeling of the saccharide rings. Using these materials, we have been able to assign the 13C and 1H spectra and to characterize various impurities on the resin beads. Copyright © 2004 John Wiley & Sons, Ltd.
Which motor nerve conduction study is best in ulnar neuropathy at the elbow?
Authors: Shakir Ali , Micklesen Paula J. , Robinson Lawrence R.
Published: March 2004

There is debate regarding how best to utilize ulnar motor nerve conduction velocity (MNCV) to identify ulnar neuropathy at the elbow (UNE). We used receiver operator characteristic (ROC) curves to compare absolute across‐elbow MNCV with MNCV difference between elbow and forearm segments (VDIF) when recording from abductor digiti minimi (ADM) and first dorsal interosseous (FDI) muscles. Also, we determined how their utility was impacted by low amplitudes of compound muscle action potentials (CMAPs). We studied 85 subjects with UNE and 77 subjects with carpal tunnel syndrome but without clinical evidence of UNE. The UNE group was divided into three subgroups based on CMAP amplitude. At 95% specificity, MNCV sensitivities were 80% at ADM and 77% at FDI, and VDIF sensitivities were 51% at ADM and 38% at FDI. The ROC curves showed MNCV to be superior to VDIF across all amplitude subgroups; however, confidence intervals overlapped when amplitude was high. Muscle Nerve 29: 585–590, 2004
Genomic organization and mutation analysis of three candidate genes for hereditary neuralgic amyotrophy
Authors: Hünermund Gert , Schirmacher Anja , Ringelstein Bernd , Young Peter , Watts Giles D. , Meuleman Jan , Nelis Eva , Chance Phillip F. , Timmerman Vincent , Stögbauer Florian , Kuhlenbäumer Gregor
Published: March 2004

Hereditary neuralgic amyotrophy (HNA) is an autosomal‐dominant inherited recurrent focal neuropathy affecting mainly the brachial plexus. In this study we report the genomic structure and mutation analysis of three candidate genes: sphingosine kinase 1 (SPHK1); tissue inhibitor of metalloproteinase 2 (TIMP2); and cytoglobin (CYGB). We did not find any disease‐associated mutations, indicating that HNA is not caused by point mutations in these genes. However, we identified several sequencing errors in the cDNA of SPHK1 as well as seven novel single‐nucleotide polymorphisms. Muscle Nerve 29: 601–604, 2004
On the behavior and shape of mixture failure rates from a family of IFR Weibull distributions
Authors: Wondmagegnehu Eshetu T.
Published: March 2004

Populations of many types of component are heterogeneous and often consist of a small number of different subpopulations. This is called a mixture and it arises in a number of situations. For example, a majority of products in industrial populations are mixtures of defective items with shorter lifetimes and standard items with longer lifetimes. It is a well‐known result that distributions with decreasing failure rates are closed under mixture. However, mixtures of distributions with increasing failure rates are not easily classifiable. If the subpopulations involved in the mixture have increasing failure rates, there might be some upward movement in the mixture and later a general downward pull towards the strongest component. Little work has been done in describing the shape of mixture failure rates when all subpopulations do not have decreasing failure rate. In this paper, we present general results that describe the shape and behavior of a failure rate of a mixture obtained from two Weibull subpopulations with strictly increasing failure rates. © 2004 Wiley Periodicals, Inc. Naval Research Logistics, 2004
1H NMR spectroscopic method for diagnosis of malabsorption syndrome: a pilot study
Authors: Bala Lakshmi , Nagana Gowda G. A. , Ghoshal U. C. , Misra A. , Bhandari M. , Khetrapal C. L.
Published: March 2004

Despite its well‐documented limitations, colorimetry has been commonly used for the d‐xylose test in the diagnosis of malabsorption syndrome (MAS). With a possibility of overcoming its limitations, the use of 1H NMR spectroscopy for D‐xylose test is explored herein. Urine samples from 35 adults with suspected MAS were obtained before and after oral ingestion of D‐xylose. The diagnosis of MAS was based on fecal fat (72 h excretion using Van de Kamer's technique, normal < 7 g/24 h and/or Sudan III stain of spot stool specimen, normal≤10 droplets/high power field) and/or endoscopic duodenal biopsy. Urinary excretion of D‐xylose over 5 h after consumption of 5 g D‐xylose, using both colorimetry and NMR was compared (normal≥1 g/5 g/5 h). In vitro experiments on the standard specimens of D‐xylose were also performed independently using both methods. Colorimetry showed a lower value for the quantity of D‐xylose excreted in urine than NMR [median 0.73 (0.17–1.89 g) vs 1.37 (0.17–3.23 g), respectively; p<0.0001, Wilcoxon's signed ranks test]. Colorimetry and NMR correctly diagnosed 11/12 and 10/12 (p=N.S.) patients with MAS and 14/23 and 20/23 (p<0.05) without MAS, respectively. Sensitivity and specificity of colorimetry and NMR were 91.6 and 60.7% vs 83.3 and 86.9%, respectively. In in vitro experiments, the values obtained for standard xylose using NMR showed a maximum error of 7%, whereas the colorimetric method showed 20%. The NMR method is simple and may be more accurate for the D‐xylose absorption test. Colorimetry was found to be inferior as compared with NMR due to its low specificity. Copyright © 2004 John Wiley & Sons, Ltd.
Error estimates for a finite volume element method for parabolic equations in convex polygonal domains
Authors: Chatzipantelidis P. , Lazarov R. D. , Thomée V.
Published: March 2004

We analyze the spatially semidiscrete piecewise linear finite volume element method for parabolic equations in a convex polygonal domain in the plane. Our approach is based on the properties of the standard finite element Ritz projection and also of the elliptic projection defined by the bilinear form associated with the variational formulation of the finite volume element method. Because the domain is polygonal, special attention has to be paid to the limited regularity of the exact solution. We give sufficient conditions in terms of data that yield optimal order error estimates in L2 and H1. The convergence rate in the L∞ norm is suboptimal, the same as in the corresponding finite element method, and almost optimal away from the corners. We also briefly consider the lumped mass modification and the backward Euler fully discrete method. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2004
A new class of stabilized mesh‐free finite elements for the approximation of the Stokes problem
Authors: Srinivas Kumar V. V. K. , Rathish Kumar B. V. , Das P. C.
Published: March 2004

Previously, we solved the Stokes problem using a new linear‐constant stabilized mesh‐free finite element based on linear Weighted Extended B‐splines (WEB‐splines) as shape functions for the velocity approximation and constant extended B‐splines for the pressure (Kumar et al., 2002). In this article we derive another linear‐constant element that uses the Haar wavelets for the pressure approximation and a quadratic‐linear element that uses quadrilateral bubble functions for the enrichment of the velocity approximation space. The inf‐sup condition or Ladyshenskaya‐Babus̆ka‐Brezzi (LBB) condition is verified for both the elements. The main advantage of these new elements over standard finite elements is that they use regular grids instead of irregular partitions of domain, thus eliminating the difficult and time consuming pre‐processing step. Convergence and condition number estimates are derived. Numerical experiments in two space dimensions confirm the theoretical predictions. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2004.
MRI morphometric and neuropsychological correlates of long‐term memory in survivors of childhood leukemia
Authors: Hill Dina E. , Ciesielski Kristina T. , Hart Blaine L. , Jung Rex E.
Published: March 2004

Background

Long‐term survivors of acute lymphoblastic leukemia (ALL) are reported to have post‐treatment neurological changes as well as neuropsychological changes. Few studies have investigated the relationship between magnetic resonance imaging (MRI) volumetric measurements of brain regions of interest and cognitive functioning. This study examined the relationship between hippocampal volumes and long‐term memory abilities in survivors of ALL.

Procedure

Ten survivors of ALL and ten matched controls underwent MRI acquisition. The participants completed a battery of tests measuring both visual and verbal long‐term memory. Volumetric measurements of the hippocampus were obtained by consecutive manual tracing using the NIH Image 1.52 program. Estimates of whole brain volume were also obtained.

Results

No significant group differences were found in right or left hippocampi. Nor were there significant differences between the two groups on measures of long‐term memory. Correlations between volumetric measurements of the hippocampus and measures of long‐term memory were non‐significant.

Conclusions

Our hypothesis of deficits in both long‐term memory and its neural substrates was not supported. It was concluded that the hippocampus, as an early developing structure, may be less vulnerable to chemotherapy treatment. Children surviving ALL are able to retain and retrieve once learned information comparable with peers. Pediatr Blood Cancer 2004;42:611–617. © 2004 Wiley‐Liss, Inc.
Ototoxicity following pediatric hematopoietic stem cell transplantation: A prospective cohort study
Authors: Punnett Angela , Bliss Bonnie , Dupuis L. Lee , Abdolell Mohamed , Doyle John , Sung Lillian
Published: March 2004

Background

Our objectives were to describe the frequency and determine risk factors for hearing deterioration following pediatric stem cell transplantation (SCT).

Methods

In this prospective cohort study, we performed pure tone audiometry and measured otoacoustic emissions (OAE) prior to and following SCT. Worse hearing was considered deterioration in either audiometry or OAE.

Results

Between October 2000 and November 2002, 45 informative audiometry or OAE results were obtained. Hearing deteriorated following SCT in 20/45 (44%) of these children. Those with worse hearing following SCT were more likely to have neuroblastoma (odds ratio [OR] 16.0 [95% CI 1.8, 143.2; P = 0.003]), receive carboplatin conditioning (OR 7.7 [95% CI 1.4, 41.9; P = 0.01]), have abnormal baseline hearing (OR 5.1 [95% CI 1.3, 19.5; P = 0.02]), and have higher baseline serum creatinine (OR for every increase of 5 μmol/L of serum creatinine of 1.5 [95% CI 1.03, 2.1; P = 0.03]).

Conclusion

Many children who undergo SCT will have deterioration in hearing following SCT. A high‐risk group of children can be delineated who may bene fit from more intensive audiological monitoring following SCT. © 2004 Wiley‐Liss, Inc.
Steroids and triterpenes from Eleocharis acutangula and E. sellowiana (cyperaceae)
Authors: Amaral Maria do Carmo E. , Faria Aparecida D. , Magalhães Aderbal F. , Magalhães Eva G. , Ruiz Ana Lúcia T. G.
Published: March 2004

From the hexane extract of the underground parts of Eleocharis acutangula (Roxb.) Schult., lup‐20(29)‐ene‐3β,16β‐diol and a mixture of campesterol, stigmasterol and sitosterol were isolated. The hexane extracts of aerial and underground parts of E. sellowiana Kunth furnished two new substances, namely neohop‐13(18)‐en‐3α‐ol and stigmast‐22‐en‐3β,6β,9α‐triol, together with a mixture of steroids, betulinic acid, stigmast‐4‐en‐6β‐ol‐3‐one and fern‐9(11)‐en‐3α‐ol. The molecular structures were determined by spectral analysis (1D‐ and 2D‐NMR experiments and MS) and comparison with literature data. Copyright © 2004 John Wiley & Sons, Ltd.
Psychosocial factors at the workplace—do they affect substance use? Evidence from the Tyrolean workplace study
Authors: Traweger C. , Kinzl Johann F. , Traweger‐Ravanelli B. , Fiala M.
Published: March 2004

Background

To determine the prevalence of drug consumption and the impact of workplace demands and burdens for substance use, we conducted a survey in a representative sample of Tyrolean employees.

Methods

This analysis was restricted to the 700 respondents (395 male, 305 female; age 18–60 years) in the year 2001 by telephone interview who hold a full‐time or part‐time job during the 6 months preceding the interview. We studied the use of antidepressants, benzodiazepines, analgetics. stimulants and phytotherapeutics.

Results

Of the whole sample, 5.6% employees (4.8% male, 6.6% female) stated that they take some kind of pills to cope with job demands. There was no statistically significant difference between males and females. Substance use depended to a great extent on the work atmosphere and job satisfaction. The prevalence of drug consumption increased from 3.7% (good atmosphere at work) and 3.3% (high job satisfaction) to 12.6% (bad atmosphere at work) and 42.9% (low job satisfaction ) (p = 0.019 and p = 0.001). The feeling of being a victim of bullying at work appears to be particularly destructive for the individuals' well‐being. Only 4.1% of the employees who were not victims of bullying took drugs because of job problems, as compared with 20% of the bullying victims.

Discussion

Our results indicate that drug consumption as the consequence of workplace burdens is a frequent and serious problem with negative consequences for the life quality of the individuals and for the individuals' efficiency. Therefore, occupational medicine and employers should direct their attention to ensure the best possible work place structure and occupational conditions. Copyright © 2004 John Wiley & Sons, Ltd.
Extent of branching from linear viscoelasticity of long‐chain‐branched polymers
Authors: Robertson Christopher G. , García‐Franco César A. , Srinivas Srivatsan
Published: March 2004

We present new results and examine literature data concerning the linear viscoelastic behavior of polyethylene with sparse to intermediate levels of long‐chain branching (LCB). These branched polymers displayed a common rheological signature, namely, a region of frequency‐independent loss tangent along with the corequisite scaling of the storage and loss moduli to the same frequency exponent. This apparent power‐law response occurred within a finite frequency window and bore resemblance to the behavior of physical gels. The appearance of this region, however, was the consequence of the presence of two distinct, yet partially overlapping, terminal relaxation processes. After considering the analogous relaxation behavior of wholly linear polymers with bimodal molecular weight distributions, we considered the polymers with LCB as blends of linear and branched species to develop a simple method of quantifying the extent of LCB. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1671–1684, 2004
Supportive‐expressive group therapy: The transformation of existential ambivalence into creative living while enhancing adherence to anti‐cancer therapies
Authors: Kissane David W. , Grabsch Brenda , Clarke David M. , Christie George , Clifton Diane , Gold Stan , Hill Christine , Morgan Ann , McDermott Fiona , Smith Graeme C.
Published: March 2004

Supportive‐Expressive Group Therapy (SEGT) has been developed and manualised in the research setting, but there have been few clinical accounts of its utility. In this qualitative review of its application in the Melbourne‐based randomised control trial (RCT) for women with advanced breast cancer, SEGT is considered from the perspective of the structure and framework of therapy, its therapists, the issues that develop in exploring its common themes and what constitutes a well functioning group. Groups move through identifiable developmental phases. The mature group process transforms existential ambivalence into creative living, evidenced by humour, celebration, assertiveness, altruism, new creative pursuits and eventually courageous acceptance of dying. Challenges and pitfalls include avoidance, non‐containment of ambivalence, intolerance of difference, anti‐group phenomena and splitting. A key element is the medicalization of the group culture whereby members and co‐therapists explore health beliefs and attitudes about care. This promotes compliance with anti‐cancer treatments, including both the initiation of and perseverance with chemotherapy. This mechanism could prove to be a potentially important pathway in promoting longer survival. Copyright © 2004 John Wiley & Sons, Ltd.
Emotional control in Chinese female cancer survivors
Authors: Ho Rainbow T.H. , Chan Cecilia L.W. , Ho Samuel M.Y.
Published: March 2004

Chinese persons are not known as strong in expressing emotions, especially negative ones. However, being diagnosed with cancer and going through treatment can be an emotionally traumatic experience and cancer patients are supposed to have a stronger need to express these negative feelings. The control of expression of negative emotions such as anger, anxiety and depression in Chinese female cancer survivors (n=139) was examined in the present study using the Chinese version of the Courtauld Emotional Control Scale (CECS). The reliability, internal consistency and validity of the Chinese CECS were comparable to the original English scale. Correlation analyses suggested that cancer survivors with higher emotional control tended to have higher stress, anxiety and depression levels and to adopt negative coping with cancer. Regression analysis showed that emotional control would positively predict stress level even after the effect of depressed mood was under control. Further investigations are suggested in order to elucidate the causal relationships and specific cultural factors affecting emotional control in Chinese cancer survivors and, most importantly, its effect on health outcomes. Copyright © 2004 John Wiley & Sons, Ltd.
Predictors of adherence and contamination in a randomized trial of exercise in colorectal cancer survivors
Authors: Courneya Kerry S. , Friedenreich Christine M. , Quinney H. Arthur , Fields Anthony L.A. , Jones Lee W. , Fairey Adrian S.
Published: March 2004

The purpose of this study was to examine predictors of exercise adherence (i.e. exercise in the intervention group) and exercise contamination (i.e. exercise in the control group) in a randomized controlled trial of home‐based exercise in colorectal cancer survivors. At baseline, 102 participants completed measures of the theory of planned behavior, personality, past exercise, exercise stage of change, physical fitness, and medical/demographics and then were randomly assigned in a 2:1 ratio to an exercise (n=69) or control (n=33) group. Exercise was monitored weekly for 16 weeks using self‐reports by telephone. Ninety‐three (91%) participants completed the trial. Adherence was 76% in the exercise group and contamination was 52% in the control group. Hierarchical stepwise regression analyses indicated that baseline exercise stage of change (β=0.35; p=0.001), employment status (β=−0.28; p=0.010), treatment protocol (β=−0.26; p=0.018), and perceived behavioral control (β=0.20; p=0.055) explained 39.6% of the variance in exercise adherence. Intentions (β=0.36; p=0.049) and baseline exercise stage of change (β=0.30; p=0.095) explained 29.9% of the variance in exercise contamination. These findings may have implications for conducting clinical trials of exercise in colorectal cancer survivors and for promoting exercise to colorectal cancer survivors outside of clinical trials. Copyright © 2004 John Wiley & Sons, Ltd.
Androgen receptor polymorphisms and risk of biochemical failure among prostatectomy patients
Authors: Strom Sara S. , Gu Yun , Zhang Hui , Troncoso Patricia , Babaian Richard J. , Pettaway Curtis A. , Shete Sanjay , Spitz Margaret R. , Logothetis Christopher J.
Published: March 2004

Background

Little is known about the role of inherited genotypes in prostate cancer (PC) progression. This prospective study evaluated the predictive value of androgen receptor (AR) polymorphisms (CAG and GGC repeats) among prostatectomy patients.

Methods

We studied 354 patients registered at M. D. Anderson Cancer Center from 1991 to 2001. Kaplan–Meier and Cox proportional hazard analyses were used.

Results

During an average follow‐up of 56 months, 66 (19%) post‐prostatectomy patients experienced biochemical failure (BF). Patients with higher CAG repeats (CAG ≥ 24) had significantly longer BF‐free survival (BFFS) than those with fewer repeats (CAG ≤ 23) (P = 0.04). Higher CAG repeats were significantly associated with lower BF risk among Whites and African Americans. Among Whites, longer CAG repeats (relative risk (RR) = 0.45,P = 0.03) and Gleason score ≥8 (RR = 19.33,P = 0.005) remained significant BFFS predictors in multivariate analysis. GGC repeats were not associated with BF.

Conclusions

Our data showed that an inherited polymorphism (CAG repeats) in the AR is related to differences in genetic susceptibility to BF, supporting the hypothesis that increased AR activity may play a role in PC progression. © 2004 Wiley‐Liss, Inc.
Mutational analysis of PINX1 in hereditary prostate cancer
Authors: Hawkins Gregory A. , Chang Bao‐Li , Zheng S. Lilly , Isaacs Sarah D. , Wiley Kathleen E. , Bleecker Eugene R. , Walsh Patrick. C. , Meyers Deborah A. , Xu Jianfeng , Isaacs William B.
Published: March 2004

Background

Telomerase activity is increased in most tumors. PinX1 has recently been identified as a critical component in regulating telomerase activity. The PinX1 gene is located within chromosomal region 8p22‐23, a region associated with LOH and potentially linked to increased prostate cancer risk.

Methods

PINX1 was re‐sequenced in 159 hereditary prostate cancer (HPC) probands. Four non‐synonymous coding variants were genotyped in 159 HPC families.

Results

Thirty‐nine polymorphisms were identified in the HPC screening panel. Ten coding polymorphisms were identified, seven (Gln50His, Leu91Met, Gln206His, Arg215Ile, Thr220Ala, Ser254Cys, and Glu414Ala) of which were non‐synonymous. The most common variants Thr220Ala and Ser254Cys were not significantly over‐transmitted from affected parent to affected offspring.

Conclusions

Based on these results, we conclude that PINX1 is not a major factor for HPC risk. © 2004 Wiley‐Liss, Inc.
Ultrahigh resolution drug design. II. Atomic resolution structures of human aldose reductase holoenzyme complexed with fidarestat and minalrestat: Implications for the binding of cyclic imide inhibitors
Authors: El‐Kabbani Ossama , Darmanin Connie , Schneider Thomas R. , Hazemann Isabelle , Ruiz Federico , Oka Mitsuru , Joachimiak Andrzejj , Schulze‐Briese Clemens , Tomizaki Takashi , Mitschler Andre , Podjarny Alberto
Published: March 2004

The X‐ray structures of human aldose reductase holoenzyme in complex with the inhibitors Fidarestat (SNK‐860) and Minalrestat (WAY‐509) were determined at atomic resolutions of 0.92 Å and 1.1 Å, respectively. The hydantoin and succinimide moieties of the inhibitors interacted with the conserved anion‐binding site located between the nicotinamide ring of the coenzyme and active site residues Tyr48, His110, and Trp111. Minalrestat's hydrophobic isoquinoline ring was bound in an adjacent pocket lined by residues Trp20, Phe122, and Trp219, with the bromo‐fluorobenzyl group inside the “specificity” pocket. The interactions between Minalrestat's bromo‐fluorobenzyl group and the enzyme include the stacking against the side‐chain of Trp111 as well as hydrogen bonding distances with residues Leu300 and Thr113. The carbamoyl group in Fidarestat formed a hydrogen bond with the main‐chain nitrogen atom of Leu300. The atomic resolution refinement allowed the positioning of hydrogen atoms and accurate determination of bond lengths of the inhibitors, coenzyme NADP+ and active‐site residue His110. The 1′‐position nitrogen atom in the hydantoin and succinimide moieties of Fidarestat and Minalrestat, respectively, form a hydrogen bond with the Nϵ2 atom of His 110. For Fidarestat, the electron density indicated two possible positions for the H‐atom in this bond. Furthermore, both native and anomalous difference maps indicated the replacement of a water molecule linked to His110 by a Cl‐ion. These observations suggest a mechanism in which Fidarestat is bound protonated and becomes negatively charged by donating the proton to His110, which may have important implications on drug design. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Polyproline II helix is the preferred conformation for unfolded polyalanine in water
Authors: Mezei Mihaly , Fleming Patrick J. , Srinivasan Rajgopal , Rose George D.
Published: March 2004

Does aqueous solvent discriminate among peptide conformers? To address this question, we computed the solvation free energy of a blocked, 12‐residue polyalanyl‐peptide in explicit water and analyzed its solvent structure. The peptide was modeled in each of 4 conformers: α‐helix, antiparallel β‐strand, parallel β‐strand, and polyproline II helix (PII). Monte Carlo simulations in the canonical ensemble were performed at 300 K using the CHARMM 22 forcefield with TIP3P water. The simulations indicate that the solvation free energy of PII is favored over that of other conformers for reasons that defy conventional explanation. Specifically, in these 4 conformers, an almost perfect correlation is found between a residue's solvent‐accessible surface area and the volume of its first solvent shell, but neither quantity is correlated with the observed differences in solvation free energy. Instead, solvation free energy tracks with the interaction energy between the peptide and its first‐shell water. An additional, previously unrecognized contribution involves the conformation‐dependent perturbation of first‐shell solvent organization. Unlike PII, β‐strands induce formation of entropically disfavored peptide:water bridges that order vicinal water in a manner reminiscent of the hydrophobic effect. The use of explicit water allows us to capture and characterize these dynamic water bridges that form and dissolve during our simulations. Proteins 2004. © 2004 Wiley‐Liss, Inc.
On the functional significance of electron density protein structure alignments
Authors: Constans Pere
Published: March 2004

Electron density protein alignments are analyzed in terms of their underlying similarity measure, the density overlap. These alignments are conceptually unrelated to biochemical structural elements and, therefore, are appropriate in structure‐only similarity studies. The analysis is focused on the low sequence similarity subset of protein domains. A remarkable association is found between simple, density overlap measures and the expert designed Structural Classification of Proteins (SCOP) for which functional and evolutive analogies prevail. The association found validates the functional significance of electron density alignments. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Discrimination of single amino acid mutations of the p53 protein by means of deterministic singularities of recurrence quantification analysis
Authors: Porrello Alessandro , Soddu Silvia , Zbilut Joseph P. , Crescenzi Marco , Giuliani Alessandro
Published: March 2004

p53 is mutated in roughly 50% of all human tumors, predominantly in the DNA‐binding domain codons. Structural, biochemical, and functional studies have reported that the different p53 mutants possess a broad range of behaviors that include the elimination of the tumor‐suppression function of wild‐type protein, the acquisition of dominant‐negative function over the wild‐type form, and the establishment of gain‐of‐function activities. The contribution of each of these types of mutations to tumor progression, grade of malignancy, and response to anticancer treatments has been so far analyzed only for a few “hot‐spots.” In an attempt to identify new approaches to systematically characterize the complete spectrum of p53 mutations, we applied recurrence quantification analysis (RQA), a non‐linear signal analysis technique, to p53 primary structure. Moving from the study of the p53 hydrophobicity pattern, which revealed important similarities with the singular deterministic structuring of prions, we could statistically discriminate, on a pure amino acid sequence basis, between experimentally characterized DNA‐contact defective and conformational p53 mutants with a very high percentage of success. This result indicates that RQA is a mathematical tool particularly advantageous for the development of a database of p53 mutations that integrates epidemiological data with structural and functional categorizations. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Apolipoprotein E‐low density lipoprotein receptor binding: Study of protein–protein interaction in rationally selected docked complexes
Authors: Prévost Martine , Raussens Vincent
Published: March 2004

Apolipoprotein E (apoE) is an important protein involved in lipid metabolism due to its interaction with members of the low‐density lipoprotein receptor (LDLR) family. To further understand the molecular basis for this receptor‐binding activity, an apoE fragment containing the receptor binding region (residues 135–151) was docked onto the fifth LDLR ligand binding repeat (LR5) by computational methods. A subset of structures generated by the docking was rationally selected on the grounds of experimental data combined with modeling and was used for further analysis.

The application and comparison of two different experimental structures for the apoE fragment underlines the local structural changes occurring in apoE when switching from a receptor‐inactive to a receptor‐active conformation. The body of interactions occurring at the interface between the two proteins is in very good agreement with the biochemical data available for both apoE and LDLR. Charged residues are involved in numerous ionic interactions and might therefore be important for the specificity of the interaction between apoE and LR5. In addition, the interface also features a tryptophan and a stacking of histidine residues, revealing that the association between the two proteins is not entirely governed by ionic interactions. In particular, the presence of histidine residues in the interface gives a structural basis for the pH‐regulated release mechanism of apoE in the endosomes. The proposed molecular basis for apoE binding to LDLR could aid the design of strategies for targeting alterations in lipid transport and metabolism. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Recognition of coarse‐grained protein tertiary structure
Authors: Lezon Timothy , Banavar Jayanth R. , Maritan Amos
Published: March 2004

A model of the protein backbone is considered in which each residue is characterized by the location of its Cα atom and one of a discrete set of conformal (ϕ, ψ) states. We investigate the key differences between a description that offers a locally precise fit to known backbone structures and one that provides a globally accurate fit to protein structures. Using a statistical scoring scheme and threading, a protein's local best‐fit conformation is highly recognizable, but its global structure cannot be directly determined from an amino acid sequence. The incorporation of information about the conformal states of neighboring residues along the chain allows one to accurately translate the local structure into a global structure. We present a two‐step algorithm, which recognizes up to 95% of the tested protein native‐state structures to within a 2.5 Å root mean square deviation. Proteins 2004;55:000–000. © 2004 Wiley‐Liss, Inc.
Fmoc‐based chemical synthesis and selective binding to supercoiled DNA of the p53 C‐terminal segment and its phosphorylated and acetylated derivatives
Authors: Teruya Kenta , Murphy Angela C. , Burlin Tom , Appella Ettore , Mazur Sharlyn J.
Published: March 2004

The C‐terminal domain of p53 comprises a linker, the tetramerization domain and the regulatory domain, and contains at least seven sites of potential post‐translational modification. An improved strategy was developed for the synthesis of large peptides that contain phosphorylated amino acids and p53(303–393), a 91‐amino acid peptide, and three post‐translationally modified derivatives were synthesized through the sequential condensation of three partially protected segments. Peptide thiolesters were prepared using the sulfonamide‐based ‘safety‐catch’ resin approach and employing Fmoc‐based solid‐phase peptide synthesis. At the N‐terminus of the middle building block, a photolabile protecting group, 3,4‐dimethoxy‐6‐nitrobenzyloxycarbonyl, was incorporated to differentiate the N‐terminal amino group from the side‐chain amino groups. Two sequential couplings were accomplished following this protection strategy. The synthetic products, p53(303–393) and its phosphorylated or acetylated derivatives, exhibited the ability to bind specifically to supercoiled DNA, which is one of the characteristics of this domain. Published in 2004 by the European Peptide Society and John Wiley & Sons, Ltd.
First‐principles periodic and semiempirical cyclic cluster calculations for single oxygen vacancies in crystalline Al2O3
Authors: Janetzko Florian , Evarestov Robert A. , Bredow Thomas , Jug Karl
Published: March 2004

Single neutral and positively charged oxygen vacancies (F and F+ centers) in α‐Al2O3 are investigated using the supercell model (SCM) at the Hartree‐Fock (HF) and density functional theory (DFT) level and the cyclic cluster model (CCM) implemented in the semiempirical MSINDO method. Results of supercell and cyclic cluster calculations for the cohesive energy of the perfect Al2O3 crystal are compared with the experimental value for the heat of atomization. The defect formation energy of the unrelaxed F center is calculated with the SCM. The CCM is used to calculate the defect formation energy of the F and the F+ centers. Relaxation effects for the nearest neighbors (NN) and the next‐nearest neighbors (NNN) of the F and F+ centers are investigated. The obtained values are compared to other theoretical literature data. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Photoelectric emission from quantum well wire: effect of broadening
Authors: Mutsuddi I. , Bose C. , Sarkar C. K.
Published: March 2004

We investigate the photoemission from quasi‐one‐dimensional electron gas (Q1DEG) formed in a quantum wire in the presence of energy level broadening arising due to electron impurity interactions in a real system. The effect of broadening has been incorporated in analogy of energy level broadening observed in a bulk semiconductor subjected to a quantizing magnetic field. Inclusion of broadening is found to be responsible for the lowering of photoemission, as expected, due to enhanced scattering. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Thickness dependence of the dielectric function of ferroelectric thin films
Authors: Wesselinowa J. M. , Trimper S.
Published: March 2004

A Green's function technique for a modified Ising model in a transverse field is applied, which allows to calculate the real and the imaginary parts of the dielectric function ϵ(k, E) for ferroelectric thin films. Compared to bulk materials the frequency of the soft‐mode in thin film is reduced whereas the damping is enhanced. The dependence of ϵ(k, E) on temperature and film thickness is obtained for k = 0 numerically. It is demonstrated, that the maximum of the dielectric function decreases with decreasing film thickness. The temperature, where the dielectric function offers a maximum, can decrease or increase depending on the strength of the surface transverse field and the exchange interaction parameter. Due to stronger damping effects in thin films the peak in the dielectric function becomes more diffuse when the film thickness decreases. The results are in reasonable qualitative agreement with experimental data for different ferroelctrics. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Horizontal line nodes in superconducting Sr2RuO4
Authors: Litak G. , Annett J. F. , Györffy B. L. , Wysokiński K. I.
Published: March 2004

Superconductivity in Sr2RuO4 is one of the most interesting phenomena in current condensed matter physics, since it is revealed to be a triplet‐pairing state. Our Editor's Choice [1] considers an important problem related to the type of order parameter in this material.

The position of line nodes on the Fermi surface, as evident from recent measurements, has been determined for various scenarios shown in the cover picture. Using these models, the temperature dependence of heat capacity and penetration depth has been calculated for easy comparison with experiments.

The first author, Grzegorz Litak, is assistant professor at Technical University of Lublin and visiting scientist at the Max Planck Institute in Dresden. He is working on the effect of disorder on correlated and exotic superconductors, nonlinear dynamics, and superconductivity in strontium ruthenate. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Neural Network Selection Mechanism for BDD Construction
Authors: Bartlett L. M.
Published: March 2004

The binary decision diagram (BDD) methodology is the latest approach used to improve the analysis of the fault ree diagram, which gives a qualitative and quantitative assessment of specified risks. To convert the fault tree into the necessary BDD format requires the basic events of the tree to be placed in an ordering. The ordering of the basic events is critical to the resulting size of the BDD, and ultimately affects the performance and benefits of this technique. A number of heuristic approaches have been developed to produce an optimal ordering permutation for a specific tree, however they do not always yield a minimal BDD structure for all trees. Latest research considers a neural network approach used to select the ‘best’ ordering permutation from a given set of alternatives. To use this approach characteristics are taken from the fault tree as guidelines to selection of the appropriate ordering permutation. This paper looks at a new method of using the Jacobian matrix to choose the most desired characteristics from the fault tree, which will aid the neural network selection procedure. Copyright © 2004 John Wiley & Sons, Ltd.
Calculating the Failure Intensity of a Non‐coherent Fault Tree Using the BDD Technique
Authors: Beeson Sally , Andrews John
Published: March 2004

This paper considers a technique for calculating the unconditional failure intensity of any given non‐coherent fault tree. Conventional fault tree analysis (FTA) techniques involve the evaluation of lengthy series expansions and approximations are unavoidable even for moderate sized fault trees. The binary decision diagram (BDD) technique overcomes some of the shortfalls of conventional FTA techniques enabling efficient and exact quantitative analysis of both coherent and non‐coherent fault trees. Copyright © 2004 John Wiley & Sons, Ltd.