bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal stabilization of the DNA duplex by adducts of aflatoxin B1
Authors: Giri Indrajit , Stone Michael P. 
Published: October 2002

AbstractThe trans‐8,9‐dihydro‐8‐(N7‐guanyl)‐9‐hydroxyaflatoxin B1 cationic guanine N7 adduct of aflatoxin B1 thermally stabilizes the DNA duplex, as reflected in increased Tm values upon adduction. The magnitude of the increased Tm value is characteristically 2–3°C. The major rotamer of the neutral guanine N7 adduct trans‐8,9‐dihydro‐8‐(2,6‐diamino‐4‐oxo‐3,4‐dihydropyrimid‐5‐yl‐formamido)‐9‐hydroxy aflatoxin B1 (the FAPY major adduct) exhibits a 15°C increase in Tm in 5′‐d(CTATFAPYGATTCA)‐3′‐5′‐d(TGAATCATAG)‐3′. Site‐specific mutagenesis experiments reveal the FAPY major adduct induces G→T mutations in Escherichia coli at a frequency six times higher than that of the cationic adduct (Smela, M. E.; Hamm, M. L.; Henderson, P. T.; Harris, C. M.; Harris, T. M.; Essigmann, J. M. Proc Natl Acad Sci USA, 99, 6655–6660). Thus, the FAPY major lesion may account substantially for the genotoxicity of AFB1. Structural studies for cationic and FAPY adducts of aflatoxin B1 suggest both adducts intercalate above the 5′‐face of the modified deoxyguanosine and that in each instance the aflatoxin moiety spans the DNA helix. Intercalation of the aflatoxin moiety, accompanied by favorable stacking with the neighboring base pairs, is thought to account for the increased thermal stability of the aflatoxin cationic guanine N7 and the FAPY major adducts. However, the structural basis for the large increase in thermal stability of the FAPY major adduct in comparison to the cationic guanine N7 adduct of aflatoxin B1 is not well understood. In light of the site‐specific mutagenesis studies, it is of considerable interest. For both adducts, the intercalation structures are similar, although improved stacking with neighboring base pairs is observed for the FAPY major adduct. In addition, the presence of the formamido group in the aflatoxin B1 FAPY major adduct may enhance duplex stability, perhaps via intrastrand sequence‐specific hydrogen bonding interactions within the duplex. © 2002 Wiley Periodicals, Inc. Biopolymers (Nucleic Acid Sci) 65: 190–201, 2002
Proposed modifications to metabolic model for glycogen‐accumulating organisms under anaerobic conditions
Authors: Zeng Raymond , Yuan Zhiguo , van Loosdrecht Mark C. M. , Keller Jürg 
Published: October 2002

AbstractFilipe et al. (2001) proposed an anaerobic metabolic model for glycogen‐accumulating organisms (GAO) in which the succinate–propionate pathway was used to describe the production of propionyl‐CoA. However, propionyl‐CoA is only an intermediate product in the above pathway. Stopping at propionyl‐CoA instead of propionate (the end product of the pathway) results in the consumption of one ATP from succinate to succinyl‐CoA, which was not accounted for in the model of Filipe et al. (2001). This resulted in significant errors in the stoichiometric coefficients in the final metabolic model. A modified model is presented in this communication and is shown to fit the experimental data significantly better than the original model. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 277–279, 2002.
Teaching and learning iterative methods for solving linear systems using symbolic and numeric software
Authors: Cariaga E. A. , Nualart M. C. 
Published: October 2002

AbstractAn integral approach is presented to strengthen the teaching and learning processes in the environment of the undergraduate course Numerical Analysis (NA) for engineering, examining tha advantages of combining the symbolic and numeric paradigms. In particular, the methodology is illustrated with the iterative methods: Gauss–Seidel (GS) and Conjugated Gradient (CG), for the numeric solution of Linear Systems (LS). The computer tools MATLAB and MAPLE are used in a pedagogic model that requires the explicit definition of Prospective Learnings and Activities of Learning. © 2002 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 51–58, 2002; Published online in Wiley InterScience (www.interscience.wiley.com.); DOI 10.1002/cae.10008
An exploratory study of the perceptions and experiences of further education amongst the young long‐term unemployed
Authors: Bolam Bruce , Sixsmith Judith 
Published: October 2002

AbstractThe aim of this study was to explore, in depth, the perceptions and experiences of Further Education (FE) amongst the young long‐term unemployed. Semi‐structured interviews were conducted with 16 long‐term unemployed youths of 18–25 years of age divided into three groups: those with no experience of FE; those having recently dropped out of FE; and those currently studying in FE. Grounded theoretical analysis highlighted the importance of both responses to and institutional aspects of unemployment. The impact of unemployment, poor previous educational experience and perceived irrelevance of FE are key barriers to learning. Those that enter FE may drop out as a result of both material and psychosocial factors. Those that stay on commonly emphasize both social support and personal agency in decision‐making alongside positive evaluations of FE. In conclusion, limitations of the findings, policy and practical recommendations for successful widening of participation in FE amongst this group are considered. Copyright © 2002 John Wiley & Sons, Ltd.
From genotype to phenotype: linking bioinformatics and medical informatics ontologies
Authors: Holloway Ele 
Published: October 2002

AbstractA small group of around 40 people came together at the Chancellors Conference Centre in Manchester for the Ontologies Workshop, chaired by Alan Rector and Robert Stevens. The workshop was, rather strangely, spread over 2 half days. In hindsight, this programme worked very well as it gave people the opportunity to chat over a drink on the Saturday evening and share ideas, before launching into the second half on the following day. The participants were from various walks of life, all with a common interest in finding out more about ontologies and promoting collaborations between the medical informatics and bioinformatics ontology communities. Copyright © 2002 John Wiley & Sons, Ltd.
Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors
Authors: Gilles Floyd H. , Leviton Alan , Tavaré C. Jane , Adelman Lester , Rorke Lucy B. , Sobel Eugene L. , Hedley‐Whyte E. Tessa , Davis Richard L. ,   The Childhood Brain Tumor Consortium
Published: October 2002

AbstractBACKGROUNDIn the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial neuroglial tumors in the Childhood Brain Tumor Consortium database.METHODSThe Cox proportional models were used to identify class survival covariates.RESULTSAge was found to be a survival covariate only in Class 1, in which older age increased the 5‐year survival rate 73% from the first year (0.49) to the tenth year (0.85). A greater amount of tumor removed improved survival in Classes 2 and 4 only. Rosenthal fibers improved survival in Class 2 and overrode the negative effects of high Proliferative factor scores and pleomorphic nuclei. Survival for Class 3 children with high Proliferative factor scores improved from 0.60 to 0.95 as the Spongy factor scores increased. Survival in Class 4 increased from 0.17 to 0.39 with total tumor removal. Irregular nuclei and glomeruloid capillaries improved survival in Class 5 patients. Class 6 survival improved with low cell density. Macrocysts in tumors in Classes 1 and 5 were found to improve survival.CONCLUSIONSAs a result of the current study, the authors conclude that survival covariates differ with tumor class and may modify prognosis considerably. Cancer 2002;95:1302–10. © 2002 American Cancer Society.DOI 10.1002/cncr.10815
Role of 5‐aminolevulinic acid in the detection of urothelial premalignant lesions
Authors: Zaak Dirk , Hungerhuber Edwin , Schneede Peter , Stepp Herbert , Frimberger Dominic , Corvin Stefan , Schmeller Nikolaus , Kriegmair Martin , Hofstetter Alfons , Knöchel Ruth 
Published: October 2002

AbstractBACKGROUNDThe authors evaluated the role of 5‐aminolevulinic acid (5‐ALA)‐induced fluorescence endoscopy (AFE) in the detection of flat urothelial lesions in light of the suggestions made for flat neoplastic lesions within the 1999 World Health Organization (WHO) classification of urinary bladder tumors.METHODSFrom 1995 to 2000, 713 patients underwent 1414 AFE procedures for the detection of transitional cell carcinoma of the bladder (TCCB). Fluorescence imaging was performed with an incoherent light source (D‐light; 380–440 nm) that was filtered for efficient protoporphyrin IX excitation and with cystoscopes partially blocking reflected excitation light to enable fluorescence evaluation by a red/blue color contrast 2–3 hours after 50 mL of a 3% solution of 5‐ALA was instilled into the bladder. In total, 3834 biopsy specimens (mean, 2.7 specimens per AFE procedure) were taken.RESULTSMalignant disease was found in 1250 (32.6%) of all biopsies, with 304 biopsies (24.3%) showing carcinoma in situ (cis) and dysplasia II° (dys II) according to the previous diagnostic criteria of the WHO. Under prior conventional white‐light endoscopy, 30.3% of specimens with dys II and 52.8% of specimens with cis had been missed.CONCLUSIONSThe current results suggest that 5‐ALA may be more effective in the detection of flat urothelial lesions than the current diagnostic devices. Cancer 2002;95:1234–8. © 2002 American Cancer Society.DOI 10.1002/cncr.10821
Patterns of multiple recurrences of superficial (Ta/T1) transitional cell carcinoma of bladder and effects of clinicopathologic and biochemical factors
Authors: Yan Yan , Andriole Gerald L. , Humphrey Peter A. , Kibel Adam S. 
Published: October 2002

AbstractBACKGROUNDAlthough multiple sequential recurrences are one of the most important characteristics of superficial transitional cell carcinoma (TCC) of the bladder, few studies have examined multiple sequential recurrence patterns and the clinicopathologic and biochemical factors associated with these patterns.METHODSTwo hundred seventy superficial TCC bladder carcinoma patients were followed. Clinical, pathologic, and tumor marker (p53, MIB‐1, bcl‐2, c‐erb B‐2, and epidermal growth factor receptor) data were collected at baseline and during followup. The Kaplan‐Meier (KM) method was used to describe multiple recurrences. The Wei, Lin, and Weissfeld (WLW) marginal proportional hazards model was used to assess the effects of clinicopathologic and immunohistochemic factors on multiple recurrences.RESULTSAmong the 270 patients, 126 (46.7%) had one or more recurrences, 38 (14.1%) had two or more recurrences, and 14 (5.2%) had three or more recurrences during the followup. The median times for the first, the second, and the third recurrences were 23 months, 15 months, and 13 months, respectively. In KM analysis, Stage T1, higher grades, and Ki‐67 stain positivity were associated with the first recurrence, and p53 stain positivity was marginally significant. Other markers were not significant. For the second recurrence, only p53 stain positivity was significant. In multivariate analysis (WLW method), stage was significantly associated with the first recurrence (risk ratio [RR] = 2.03), and Ki‐67 was marginally significant (RR = 1.49). For the second recurrence, only p53 positivity was statistically significant (RR = 2.73).CONCLUSIONSAmong superficial TCC bladder carcinoma patients, multiple recurrences are common phenomena. The time for recurrence becomes shorter as the number of recurrences increases. In addition to tumor stage and grade, Ki‐67 can be used to identify patients at high risk for a first recurrence; and p53 can be used to identify patients at high risk for a second recurrence. Cancer 2002;95:1239–46. © 2002 American Cancer Society.DOI 10.1002/cncr.10822
Prognostic significance of positive surgical margins in patients with extraprostatic carcinoma after radical prostatectomy
Authors: Kausik Sankar J. , Blute Michael L. , Sebo Thomas J. , Leibovich Bradley C. , Bergstralh Erik J. , Slezak Jeff , Zincke Horst 
Published: October 2002

AbstractBACKGROUNDA significant number of prostate adenocarcinoma patients undergoing radical prostatectomy are found to have microscopic extraprostatic disease extension. A majority of these patients have focal extraprostatic extension limited to one or both sides of the prostate. In addition, positive surgical margins are a common pathologic finding in this patient subgroup. In the current study, the authors evaluated the impact of positive surgical margins as an independent predictive factor for prostate specific antigen (PSA) progression in patients with pT3a/b N0M0 carcinoma.METHODSThe Mayo Clinic prostate cancer registry list provided 1202 patients with pT3a/b NO prostate carcinoma (no seminal vesicle or regional lymph node involvement) who underwent a radical prostatectomy between 1987–1995. To reduce confounding variables, patients who received preoperative therapy or adjuvant therapy were excluded, resulting in 842 patients who were eligible for analysis.RESULTSA total of 354 patients (42%) had ≥ 1 positive surgical margins whereas 488 patients (58%) demonstrated no margin involvement. The sites of margin positivity were as follows: apex (n = 163), base (n = 47), posterior prostate (n = 227), and anterior prostate (n = 11). A total of 111 patients had ≥ 2 positive surgical margins. The 5‐year survival free of clinical recurrence and/or biochemical failure (postoperative PSA level > 0.2 ng/mL) for patients with no positive surgical margins was 76% and was 65% for patients with 1 positive surgical margin (P = 0.0001). There was no significant difference in biochemical disease progression between patients with 1 versus those with ≥ 2 surgical margins (65% vs. 62%). Multivariate analysis revealed that positive surgical margins were a significant predictor (P = 0.0017) of clinical disease recurrence and biochemical failure (relative risk, 1.55; 95% confidence interval, 1.18–2.04) after controlling for preoperative PSA, Gleason score, and DNA ploidy.CONCLUSIONSIn the current study, positive surgical margins were found to be a significant predictor of disease recurrence in patients with pT3a/b NO prostate carcinoma, a finding that is independent of PSA, Gleason score, and DNA ploidy. The benefit of adjuvant therapy in optimizing recurrence‐free survival remains to be tested. Cancer 2002;95:1215–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10871
Central projections of the utricular nerve in the gerbil
Authors: Newlands Shawn D. , Purcell Ian M. , Kevetter Golda Anne , Perachio Adrian A. 
Published: October 2002

AbstractThe central projections of primary afferent fibers in the utricular nerve, which convey linear head acceleration signals to neurons in the brainstem and cerebellum, are not completely defined. The purpose of this investigation was twofold: 1) to define the central projections of the gerbil utricular afferents by injecting horseradish peroxidase (HRP) and biotinylated dextran amine (BDA) into the utricular macula; and 2) to investigate the projections of individual utricular afferents by injecting HRP intracellularly into functionally identified utricular neurons. We found that utricular afferents in the gerbil projected to all divisions of the vestibular nuclear complex, except the dorsal lateral vestibular nucleus. In addition, terminals were observed in the interstitial nucleus of the eighth nerve, nucleus Y, external cuneate nucleus, and lobules I, IV, V, IX, and X of the cerebellar vermis. No projections appeared in the flocculus or paraflocculus. Fibers traversed the medial and intermediate cerebellar nuclei, but terminals appeared only occasionally. Individual utricular afferents collateralize extensively, projecting to much of the brainstem area innervated by the whole of the utricular nerve. This study did not produce complete filling of individual afferent collateral projections into the cerebellar cortex. J. Comp. Neurol. 452:11–23, 2002. © 2002 Wiley‐Liss, Inc.
Targeting Alzheimer's disease: Is there a light at the end of the tunnel?
Authors: Gurwitz David 
Published: October 2002

AbstractThe prevalence of Alzheimer's disease (AD) is on the rise in developed nations as a consequence of longer human lifespan. Current costs to society are alarming, and are projected to become even more demanding on future health budgets. Considering the relative success of Parkinson's disease pharmacotherapy, the success of AD therapy has been disappointing. Quite a few novel and promising AD drug targets are presented in this special issue of Drug Development Research. These are built on countless research studies, by many bright minds, carried out over the last several decades. However, the answer to the growing AD threat must include reliable and accurate tools, presently lacking, for its early diagnosis in at‐risk individuals. Drug Dev. Res. 56:45–48, 2002. © 2002 Wiley‐Liss, Inc.
Pharmacogenomic approaches in Alzheimer's disease drug development
Authors: Aerssens Jeroen 
Published: October 2002

AbstractThe basic principle of pharmacogenomics, namely, the search for a genetic basis that might explain the interindividual variation in drug response, has been around for a long time. Thanks to some recent biotechnological developments and the deliveries of the Human Genome Project, significant progress can now be made. Of particular interest for pharmacogenomics research is the availability of a large number of genetic markers in the human genome that have been identified and can now efficiently be screened for. In addition to new scientific and laboratory tools, successful pharmacogenomics projects also require high‐quality phenotypic data, for which clinical trials provide a unique resource. This review describes how pharmacogenomic approaches can be applied during the discovery and clinical development of new drugs for Alzheimer's disease. Drug Dev. Res. 56:67–73, 2002. © 2002 Wiley‐Liss, Inc.
Immunological concept in the treatment of Alzheimer's disease
Authors: Solomon Beka 
Published: October 2002

AbstractMore and more evidence shows that Alzheimer's disease, one of the most perplexing medical problems, belongs to a large group of etiologically diverse neurodegenerative disorders, so‐called ‘conformational’ diseases. Pathology of Alzheimer's disease (AD) shows significant correlation between β‐amyloid peptide (AβP) deposition and the clinical severity of dementia. For many years efforts have been focused on the development of selective inhibitors of amyloid formation to reduce the extent of its deposition and related neurotoxic effects. We developed a new concept showing that site‐directed antibodies may modulate the conformation of β‐amyloid peptide, thus leading to immunological treatment of Alzheimer's disease as well as of other conformation related diseases. Indeed, antibodies toward the EFRH sequence, located between amino acids 3–6 of the N‐terminal region of Alzheimer's AβP, found to be a key position in protein conformation modulation, suppress formation of β‐amyloid and dissolve already formed fibrillar amyloid. Performance of such anti‐β‐amyloid antibodies in transgenic mice models of AD showed that they are delivered to the central nervous system (CNS), preventing formation of β‐amyloid and dissolving real plaques. These data support the hypothesis that AβP plays a central role in AD, and antibodies that modulate Aβ conformation may lead toward immunotherapy of the disease. Drug Dev. Res. 56:163–167, 2002. © 2002 Wiley‐Liss, Inc.
Cytosolic protein‐protein interactions that regulate the amyloid precursor protein
Authors: Sabo Shasta L. , Ikin Annat F. 
Published: October 2002

AbstractAlzheimer disease (AD), a progressive neurodegenerative disease, is the most common cause of dementia in the elderly and is among the leading causes of death in adults. AD is characterized by two major pathological hallmarks, amyloid plaques and neurofibrillary tangles. For a number of reasons, amyloid plaque accumulation is widely thought to be the probable cause of AD. The amyloid plaque core is largely composed of an approximately 4‐kDa peptide referred to as Aβ. Aβ is derived from its precursor, the Alzheimer amyloid protein precursor (APP), by endoproteolytic processing. APP is a type I integral membrane protein, with a long extracellular domain, one transmembrane domain, and a short (≈50 amino acid) cytoplasmic tail. Despite intense efforts to decipher the function of APP, its normal physiological role has remained elusive. The carboxy‐terminus of APP contains the sequence YENPTY, which is absolutely conserved across APP homologues and across species. The YENPTY sequence is important for regulation of APP processing and trafficking. Given the importance of the cytoplasmic domain in APP physiology, a number of laboratories have hypothesized that proteins that bind to the YENPTY sequence in the cytoplasmic domain of APP might regulate APP processing, trafficking, and/or function. In this article, we will discuss data revealing which proteins bind to the cytoplasmic domain of APP, how these binding‐proteins regulate APP metabolism and function, and why such protein‐protein interactions provide an exciting new target for therapeutic intervention in AD. Drug Dev. Res. 56:228–241, 2002. © 2002 Wiley‐Liss, Inc.
Anti‐amyloidogenic activity of cholinergic agents
Authors: Beach Thomas G. , Walker Douglas G. , Roher Alex E. , Potter Pamela E. 
Published: October 2002

AbstractOverproduction of the peptide amyloid β (Aβ) is thought to be a critical pathogenic event in Alzheimer's disease (AD), leading to the formation of senile (amyloid) plaques, which in turn lead to neurofibrillary tangles, neuronal and synaptic loss, and dementia. Mendelian inheritance of AD, which occurs in a very small proportion of cases, is caused by mutations in the genes for β‐amyloid precursor protein (β‐APP), presenilin 1 or presenilin 2; the mutations are thought to be pathogenic because they result in increased Aβ production. The majority of AD is not inherited in a Mendelian fashion, and is therefore termed sporadic. The cause or causes of this common form of AD is unknown, although it is assumed that overproduction of Aβ is also the critical event. Recent animal experiments suggest that Aβ overproduction in aging and sporadic AD may be the result of cortical cholinergic deafferentation, which occurs as part of normal human aging. Decreasing Aβ production may therefore slow or halt the progression of AD, and cholinergic agents may be particularly suitable for this role. In vitro work has indicated that cholinergic muscarinic M1 receptor agonists may reduce the cellular production of Aβ. In vivo experiments have shown that both muscarinic agonists and acetylcholinesterase inhibitors lower central nervous system (CNS) Aβ concentrations. These results suggest that cholinergic agents may be particularly well suited to a preventative role in AD therapy by limiting the initial accumulation of Aβ. Drug Dev. Res. 56:242–247, 2002. © 2002 Wiley‐Liss, Inc.