bluuebunny/crossref_metadata_2025 huggingface dataset:
Processes of visual self‐recognition in infants: experimental induction of ‘mirror’ experience via video self‐image presentation
Authors: Vyt Andre
Published: August 2002

This study investigates infants' (ages 15–28 months) performance on two visual self‐recognition measures: using a video‐screen as a mirror‐like medium to locate objects not seen directly, and locating a mark on the face after seeing it in the mirror‐like medium. Infants experienced one of two training conditions on the video‐screen: they watched their parents and the parents' reflected images or they watched themselves. The study aims to find evidence for the view that object‐locating and mark‐directed behaviour in self‐image presentation are in different ways experience‐dependent. Contingency experience influenced the ability to locate objects, but did not influence mark‐directed behaviour in a marked‐face (rouge) condition. Also, children with a higher level of object‐permanence understanding scored better on object‐localization, while level of object‐permanence understanding was unrelated to mark‐directed behaviour in the rouge condition. The findings suggest that mark‐ and object‐locating conditions follow a different developmental course. Search behaviour in this paradigm is also discussed with regard to experiential elements, perceptual cues and representational skills. The locating of mirrored objects may be a good paradigm for studying sensorimotor information processing, without being necessarily used as an indicator of self‐awareness. Copyright © 2001 John Wiley & Sons, Ltd.
Executive functions and development: emerging themes
Authors: Hughes Claire
Published: August 2002

Earlier in this special issue I outlined four themes that contribute to the growing research interest in studies of executive function in childhood populations. These were: (1) the importance of executive dysfunction in accounts of developmental disorders such as Autism and ADHD; (2) methodological insights arising from the development of new techniques for assessing children's emerging executive functions; (3) evidence for a fractionated or componential view of executive control; and (4) the relation between individual differences in young children's performance on tests of executive function and ‘theory of mind’. In this paper, these four themes are used to integrate the findings from all the papers in this special issue on executive functions and development. Copyright © 2002 John Wiley & Sons, Ltd.
Rule‐based reasoning and theory of mind in autism: a commentary on the work of Zelazo, Jacques, Burack and Frye
Authors: Colvert Emma , Custance Deborah , Swettenham John
Published: August 2002

This commentary is concerned with the work of Zelazo, Jacques, Burack and Frye (2002) and highlights a number of aspects of the Zelazo et al. (2002) study that raise some concern, most notably the small sample size and lack of control groups. The commentary provides details of our own research (Colvert et al., The rule‐based reasoning and theory of mind abilities of children with autism, poster presented at the biennial meeting, Society for Research in Child Development, Minneapolis, Minnesota, 2001, Rule‐based reasoning and theory of mind in children with autism, submitted), which used a larger sample and a more carefully controlled design to provide a further examination of the possible links between rule‐based reasoning and theory of mind (ToM) in autism. With these key modifications our study also found evidence of a significant link between these two aspects of development for high‐functioning children with autism. It would seem that there is evidence that the ToM abilities of children with autism may not be a separate aspect of development, but may instead be linked to more general developments in embedded reasoning skills; as stated by the Cognitive Complexity and Control theory. However, the current commentary notes that caution is required when drawing such conclusions, as all evidence thus far is correlational in nature. Copyright © 2002 John Wiley & Sons, Ltd.
Sequence variation and physical state of human papillomavirus type 16 cervical cancer isolates from Australia and New Caledonia
Authors: Watts Kylie J. , Thompson Carol H. , Cossart Yvonne E. , Rose Barbara R.
Published: August 2002

Sequence diversity over 2600 nucleotides of the upstream regulatory region (URR) and the E6 and E2/E4 genes of 34 human papillomavirus (HPV)16 cervical cancer isolates from Australia and New Caledonia was investigated. One 81 base duplication, 41 single base substitutions and 1 single base insertion were identified in the URRs. Some of these changes are reported here for the first time. Several of the 19 changes impacting transcription factor binding sites had the potential to alter promoter activity. Twenty‐eight (82%) of the variants belonged to the European lineage, 4 (12%) were Asian and 2 (6%) were Asian‐American. Eighteen of 27 (67%) isolates where the E6 gene was examined contained amino acid substitutions. Of 13 isolates sequenced with intact E2 genes, 12 (92%) contained amino acid substitutions in the E2 protein and 3 (23%) amino acid substitutions in the overlapping E4 protein. Some of the changes in E6 and E2 may alter immunological epitopes or protein function. The physical state of HPV DNA was assessed by Southern hybridization and PCR for an intact E2 gene. Overall, 11 of 25 isolates contained only integrated HPV DNA, 10 only episomal HPV DNA and 4 both integrated and episomal DNA. No particular patterns of variation in the URR, E6 or E2/E4 genes predicted physical state. This investigation represents one of the most comprehensive studies of its kind and fills an important gap in global sequence data. © 2001 Wiley‐Liss, Inc.
Meat consumption and colorectal cancer risk: Dose‐response meta‐analysis of epidemiological studies
Authors: Norat Teresa , Lukanova Annekatrin , Ferrari Pietro , Riboli Elio
Published: August 2002

The hypothesis that consumption of red and processed meat increases colorectal cancer risk is reassessed in a meta‐analysis of articles published during 1973–99. The mean relative risk (RR) for the highest quantile of intake vs. the lowest was calculated and the RR per gram of intake was computed through log‐linear models. Attributable fractions and preventable fractions for hypothetical reductions in red meat consumption in different geographical areas were derived using the RR log‐linear estimates and prevalence of red meat consumption from FAO data and national dietary surveys. High intake of red meat, and particularly of processed meat, was associated with a moderate but significant increase in colorectal cancer risk. Average RRs and 95% confidence intervals (CI) for the highest quantile of consumption of red meat were 1.35 (CI: 1.21–1.51) and of processed meat, 1.31 (CI: 1.13–1.51). The RRs estimated by log‐linear dose‐response analysis were 1.24 (CI: 1.08–1.41) for an increase of 120 g/day of red meat and 1.36 (CI: 1.15–1.61) for 30 g/day of processed meat. Total meat consumption was not significantly associated with colorectal cancer risk. The risk fraction attributable to current levels of red meat intake was in the range of 10–25% in regions where red meat intake is high. If average red meat intake is reduced to 70 g/week in these regions, colorectal cancer risk would hypothetically decrease by 7–24%. © 2001 Wiley‐Liss, Inc.
Use of H19 regulatory sequences for targeted gene therapy in cancer
Authors: Ohana Patricia , Bibi Osaat , Matouk Imad , Levy Carol , Birman Tatiana , Ariel Ilana , Schneider Tamar , Ayesh Suhail , Giladi Hilla , Laster Morris , de Groot Nathan , Hochberg Abraham
Published: August 2002

We present a tumor gene therapy approach based on the use of regulatory sequences of the H19 gene that are differentially expressed between normal and cancer cells. We constructed expression vectors carrying the gene for the A fragment of diphtheria toxin (DT‐A) or herpes simplex virus thymidine kinase (HSV‐tk), under the control of a 814 bp 5′‐flanking region of the H19 gene. The cell killing activity of these constructs was in accordance with the relative activity of the H19 regulatory sequences in the transfected cells. We evaluated the therapeutic potential of the gene expression constructs driven by H19 regulatory sequences in an animal model of bladder cancer induced by subcutaneous injection of syngeneic bladder tumor cell lines. Intratumoral injection of these constructs caused a significant suppression of subcutaneous tumor growth, with no obvious toxicity toward the host. © 2002 Wiley‐Liss, Inc.
Short‐term sexual function after prostate brachytherapy
Authors: Merrick Gregory S. , Wallner Kent , Butler Wayne M. , Lief Jonathan H. , Sutlief Steven
Published: August 2002

Sexual function was evaluated in 34 patients with low‐risk prostate cancer (PSA ≤ 10, Gleason score ≤ 6, clinical stage T1/T2) undergoing brachytherapy in a phase III prospective randomized trial comparing iodine‐125 (125I) to palladium‐103 (103Pd). The mean and median International Index of Erectile Function (IIEF) scores for the entire group were 14.2 and 16.5, respectively, and there was no difference between these scores when stratified by isotope. IIEF scores < 6, 6 to 11, and ≥ 12 were recorded in 35% (12/34), 6% (2/34), and 59% (20/34) of patients, respectively. Hematospermia, orgasmalgia (pain at the time of orgasm), and alteration in intensity of orgasm were documented in 26% (9/34), 15% (5/34), and 38% (13/34) of patients, respectively, but these side effects were of limited duration for most patients. There was no relationship between radiation dose to the neurovascular bundles (NVB), which averaged 209% of the prescribed prostate dose, and the development of postbrachytherapy impotence. All four impotent patients who used sildenafil responded favorably. With a median follow‐up of 13 months, 65% of patients undergoing prostate brachytherapy maintained sexual function without pharmacologic support. Including sildenafil responses, 76.5% of patients sustained erections sufficient for sexual intercourse. 2001 Wiley‐Liss, Inc.
Analysis of mutations and identification of several polymorphisms in the putative promoter region of the P34CDC2‐related CDC2L1 gene located at 1P36 in melanoma cell lines and melanoma families
Authors: Feng Yongmei , Shi Jiaqi , Goldstein Alisa M. , Tucker Margaret A. , Nelson Mark A.
Published: August 2002

Chromosome 1 abnormalities are the most commonly detected aberrations in many cancers including malignant melanoma. Partial deletions and an allelic loss of the chromosome 1p36 region observed in melanoma indicate the presence of putative tumor suppressor gene(s) in this region. A candidate gene, CDC2L1, which encodes PITSLRE proteins related to p34cdc2, is mapped to 1p36. To determine whether CDC2L1 mutation is involved in melanoma development, we examined 20 melanoma cell lines and 11 members of melanoma‐prone families linked to chromosome 1p36. Mutation analysis throughout the entire coding region of the CDC2L1 gene revealed only 1 mutation (C→T at nucleotide location 97 of exon 7, Ser→Leu) in the melanoma cell line UACC 903 out of 20 melanoma cell lines and 6 melanoma cases. However, 4 polymorphic nucleotide changes, C‐48T, G‐53C, T‐103C and T‐210C, in the putative promoter region of CDC2L1 were identified. The 4 variants were located within or beside the conserved binding sites of transcription factors TCF11, MZF1 and TAAC box, indicating their potential effects on the regulation of CDC2L1 expression. No aberrant methylation of the CDC2L1 CpG island in the promoter region was observed by sodium bisulfite genomic sequencing. These results indicate that mutations are rare in the CDC2L1 gene in these melanoma cell lines and melanoma families and that the aberrant cytosine methylation of the CDC2L1 CpG island is not the mechanism of CDC2L1 repression in melanoma. The contribution of 4 promoter polymorphisms to the transcriptional regulation of the gene and its association with melanoma warrants further investigation. © 2002 Wiley‐Liss, Inc.
Possible role of galectin‐9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance
Authors: Kageshita Toshiro , Kashio Yumiko , Yamauchi Akira , Seki Masako , Abedin Mohammad Jainul , Nishi Nozomu , Shoji Hiroki , Nakamura Takanori , Ono Tomomichi , Hirashima Mitsuomi
Published: August 2002

Galectin‐9 expression was examined in 6 human melanoma cell lines. Among them, MM‐BP proliferated with colony formation, but MM‐RU failed. RT‐PCR analysis revealed evident expression of galectin‐9 mRNA in MM‐BP but not in MM‐RU. MM‐BP expressed galectin‐9 protein both on the surface and in the cytoplasm, whereas MM‐RU expressed it only weakly in the cytoplasm. Exogenous galectin‐9 induced in vitro both cell aggregation and apoptosis of MM‐RU proliferating without colony formation. Association of galectin‐9 expression in melanoma cells with prognosis of the patients bearing melanocytic tumors was further examined. Galectin‐9 protein was strongly and homogeneously expressed in melanocytic nevi, but down‐regulated in melanoma cells especially in metastatic lesions. High galectin‐9 expression was inversely correlated with the progression of this disease, suggesting that high galectin‐9 expression in primary melanoma lesions links to a better prognosis. © 2002 Wiley‐Liss, Inc.
Workplace mobility and occupational achievement
Authors: van Ham Maarten
Published: August 2002

This paper reports an investigation of the effects on occupational achievement of workplace mobility, that is, accepting a job over a longer distance. We extend the classical conceptualisation of the relationship between spatial flexibility and occupational achievement by including not only long‐distance migration, but also long‐distance commuting as an instrument of career advancement. Using longitudinal data, with job change as the unit of analysis, career advancement is measured directly by comparing the level of the accepted job with the level of the former job. The results show that workplace mobility is indeed instrumental in career advancement. Workers who accept jobs over a longer distance make more career advancement after a job change than workers who accept jobs closer to their residence. Women with a partner form an exception. For them, workplace mobility has no effect on career advancement. A probable explanation is a tied‐mover effect. Some women with a partner accept a job over a longer distance for the sake of the career of the male spouse and because the household as a whole migrates. So the conclusion is that for women, workplace mobility is only instrumental in career advancement when a job is accepted over a long distance for their own career. Copyright © 2001 John Wiley & Sons, Ltd.
Shifting sex differentials in mortality during urban epidemiological transition: the case of Victorian London
Authors: Mooney Graham
Published: August 2002

Unlike some forms of mortality inequality, sex differentials in England and Wales increased unequivocally during the Victorian era. A gradual reversal of this trend was observed only recently. The origin of the widened mortality gap between males and females lies in the transformation of the epidemiological landscape during the second half of the nineteenth century, from one where epidemic and endemic infectious diseases dominated, to one where chronic, degenerative conditions began to prevail. This so‐called ‘epidemiological transition’ had differential impacts on males and females through time and in space, partly because mortality change was mediated by socially constructed gender roles. Research on rural and urban contrasts has shown consistent excess female mortality in youth and early adulthood. But because London did not exhibit this particular sex bias in the Victorian period, examination of internal variations in the capital offers an opportunity to explore the influence of factors that varied within the urban environment. Using life table decomposition, the article reveals that contrasts in cause‐specific mortality between boys and girls and elderly men and women contributed most forcefully to overall male/female differences in life expectation at birth. Copyright © 2002 John Wiley & Sons, Ltd.
Editorial introduction: (re)theorising population geography: mapping the unfamiliar
Authors: Graham Elspeth , Boyle Paul
Published: August 2002

In recent years, population geography has become increasingly marginalised within its parent discipline as a result of its failure to engage with the ‘new’ human geographies. Despite notable successes in some areas, contemporary population geography is characterised by a methodological conservatism and an inattention to theory that could prove detrimental to its future prospects. In 2000, a conference was held at the University of St. Andrews to discuss openings for (re)theorising population geography. This special issue arises from that conference and is devoted to stimulating debate about possible ‘new’ and more theoretically grounded population geographies. Whilst not intended as a blueprint for how any (re)theorisation might be conceptualised, the six papers cover a variety of topics and address different ways in which population geography might seek to re‐orientate its research agenda. Copyright © 2001 John Wiley & Sons, Ltd.
New forms of migration into the European South: challenges for citizenship and governance – the Portuguese Case
Authors: Fonseca Maria Lucinda , Caldeira Maria José , Esteves Alina
Published: August 2002

Since the mid‐1980s, Portugal has altered its position in the international migration context. It is no longer exclusively an emigration country but has also become a receiving nation, hosting people from its former African colonies, and more recently from Brazil and Eastern Europe. This has caused significant changes in Portuguese society, which is nowadays socially more diverse and ethnically richer. This paper identifies the most important challenges to citizenship and governance in Portugal, focusing on: (a) the changes in the national laws regulating immigration; (b) the measures adopted by central government to fight discrimination; and (c) the growing social exclusion faced by many immigrants. Among the adopted measures, the new law regulating the entry and permanence of foreigners in Portugal, the establishment of a High Commissioner for Immigration and Ethnic Minorities (ACIME), the growing role of immigrants' associations, and the responsibilities transferred to local authorities are closely analysed. Drawing on analysis of interviews and questionnaires addressed to civil servants working in departments related to immigration as well as on reports published by municipalities in the Lisbon Metropolitan Area (LMA), the article also investigates the strategies adopted by local authorities to promote the successful integration of immigrants. The evidence indicates that there is a growing feeling among local authorities that their resources should be oriented to work with the citizens and not just for the citizens. To guarantee future sustainable development, citizens, regardless of their geographical origin, should have a say in the decision‐making processes at a local level. Copyright © 2002 John Wiley & Sons, Ltd.
Investigation of smooth basis functions and an approximated projection algorithm for faster tomography
Authors: Rydesäter Peter , Gustavsson Björn
Published: August 2002

To decrease the calculation time of iterative tomographic reconstruction, this study proposes and investigates the uses of the “dot‐projection” algorithm, which uses smooth basis functions for data representation. Basis functions give an approximation to the basis functions of blobs, which provide a more accurate reconstruction at the same resolution than for traditional “ray‐driven” projection algorithms with voxels. This study evaluates the calculation time decrease and obtained errors from the algorithm for reconstruction, as well as its response to spatial frequencies. Finally, we compare the dot‐projection for several basis functions and the ray‐driven projection with respect to accuracy. © 2001 John Wiley & Sons, Inc. Int J Imaging Syst Technol 11, 347–354, 2000
Mother–child interaction and sleep regulation in one‐year‐olds
Authors: Scher Anat
Published: August 2002

The regulation of sleep–wake states is controlled not only by biological mechanisms but by care‐giving context as well. In this study the association between mother–child relationship and the infant's sleep was examined. Thirty‐seven 12‐month‐olds and their mothers participated in a 10‐minute laboratory play episode. The dyadic interaction was coded with the Early Parent–Child Relational Assessment (Clark, 1985) and with the Emotional Availability scales (Biringen, Robinson, & Emde, 1993). The child's sleep was measured at home with a small‐computerized activity monitor. Although mothers' behavior was not related to the child's sleep, infants who were more responsive in the play episode woke up more frequently compared to infants who were less involved in the interaction. The link between social‐emotional competency and fragmented sleep, among nonrisk infants, could be an age‐related phenomenon. ©2001 Michigan Association for Infant Mental Health.
Revenue
Authors: Zemsky Robert , Shaman Susan , Shapiro Daniel B.
Published: August 2002

This chapter discusses how the pursuit of revenue accelerated the shift from institutional to market perspectives across U.S. institutions of higher education.
Contours
Authors: Zemsky Robert , Shaman Susan , Shapiro Daniel B.
Published: August 2002

Touring across the various market segments, this chapter demonstrates how faculty salaries, faculty‐student ratios, use of part‐time faculty, and student choice follow the ordering of the market.
Effects of pond water, sediment and sediment extract samples from new hampshire, usa on early Xenopus development and metamorphosis: comparison to native species
Authors: Fort Douglas J. , Rogers Robert L. , Paul Robbin R. , Miller Mark F. , Clark Patrick , Stover Enos L. , Yoshioko Joy , Quimby Fred , Sower Stacia A. , Reed Karen L. , Babbitt Kimberly J. , Rolland Rosalind
Published: August 2002

In an effort to assess potential ecological hazards to amphibian species in selected regions within New Hampshire, the traditional Frog Embryo Teratogenesis Assay—Xenopus (FETAX), a 14‐/21 day tail resorption thyroid disruption assay and >30 day limb development tests were conducted with representative surface water and sediment samples. Two separate sets of samples collected from five sites were evaluated. The primary objectives of the study were to determine if samples were capable of inducing early embryo‐larval maldevelopment, to determine if maldevelopment included limb defects, to determine if thyroxine co‐administration altered the rates of limb malformation and to evaluate the impact of the samples on growth rates, developmental progress and metamorphic climax. Results from these studies suggested that pond water and sediment extract samples, but not whole sediment samples, from B2, FW, LP and W ponds were capable of inducing abnormal early embryo‐larval development. In addition, water samples from B2 and W ponds induced significant abnormal hindlimb development. Some abnormal forelimb development was noted in the tail resorption studies, but not to the same extent as the hindlimbs. Each of the water samples induced appreciable developmental delay, including the paired reference site B1, which could be reversed by the addition of exogenous thyroxine. Copyright © 2001 John Wiley & Sons, Ltd.
Production of superoxide anion, lipid peroxidation and DNA damage in the hepatic and brain tissues of rats after subchronic exposure to mixtures of TCDD and its congeners
Authors: Hassoun Ezdihar A. , Li Feng , Abushaban Ahmed , Stohs Sidney J.
Published: August 2002

In this study the induction of oxidative stress in the hepatic and brain tissues of rats after subchronic exposure to various mixtures of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and two of its congeners, namely 2,3,4,7,8‐pentachlorodibenzofuran (PeCDF) and 3,3′,4,4′,5‐pentachlorobiphenyl (PCB 126) was investigated. Four mixtures of TCDD and its congeners, corresponding to 10, 22, 46 and 100 ng of toxic equivalence (TEQ) kg−1 day−1, were administered to groups of rats for 13 weeks. The animals were sacrificed at the end of the exposure period and the biomarkers of oxidative stress, including the production of superoxide anion, lipid peroxidation and DNA single‐strand breaks (SSBs), were determined in the hepatic and brain tissues. All mixtures caused dose‐dependent increases in the production of superoxide anion, lipid peroxidation and DNA SSBs in both tissues, with significantly higher damage in the hepatic compared with the brain tissues. The 22 ng TEQ dose level (TEQ = 22) contains TCDD, PeCDF and PCB 126 at levels that correspond to 7.3, 14.5 and 73.3 ng kg−1 day−1, respectively, and it produced effects that correspond to ca. 50% of the maximal production of superoxide anion, lipid peroxidation and DNA SSBs in the hepatic and brain tissues of those animals. Relative to the doses that are required to produce 50% of the maximal production of the biomarkers of oxidative stress by the individual congeners in hepatic and brain tissues of rats, the concentrations of the congeners in TEQ = 22 did result in significant interactivity, probably in the form of additive effects in the hepatic but not in brain tissues. Copyright © 2001 John Wiley & Sons, Ltd.
Site‐specific percutaneous absorption of methyl salicylate and VX in domestic swine
Authors: Duncan E. J. Scott , Brown April , Lundy Paul , Sawyer Thomas W. , Hamilton Murray , Hill Ira , Conley John D.
Published: August 2002

The site specificity of the percutaneous absorption of methyl salicylate (MeS) and the organophosphate nerve agent VX (O‐ethyl S‐(2‐diisopropylaminoethyl) methylphosphonothioate) was examined in anaesthetized domestic swine that were fully instrumented for physiological endpoints. Four different anatomical sites (ear, perineum, inguinal crease and epigastrium) were exposed to the MeS and the serum levels were measured over a 6‐h time period. The dose absorbed at the ear region was 11 μg cm−2 with an initial flux of 0.063 μg cm−2min−1, whereas at the epigastrium region the dose absorbed was 3 μg cm−2 with an initial flux of 0.025 μg cm−2min−1. For this reason further studies were carried out with VX on the ear and the epigastrium only. In animals treated with agent on the epigastrium, blood cholinesterase (ChE) activity began to drop 90 min after application and continued to decline at a constant rate for the remainder of the experiment to ca. 25% of awake control activity. At this time there were negligible signs of poisoning and the medical prognosis was judged to be good. In contrast, the ChE activity in animals receiving VX on the ear decreased to 25% of awake control values within 45 min and levelled out at 5–6% by 120 min. Clinical signs of VX poisoning paralleled the ChE inhibition, progressing in severity over the duration of the exposure. It was judged that these animals would not survive. The dramatic site dependence of agent absorption leading to vastly different toxicological endpoints demonstrated in this model system has important ramifications for chemical protective suit development, threat assessment, medical countermeasures and contamination control protocols. Copyright © 2002 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Hydroxyapatite coating on titanium by thermal substrate method in aqueous solution
Authors: Kuroda Kensuke , Ichino Ryoichi , Okido Masazumi , Takai Osamu
Published: August 2002

A new hydrocoating method (the thermal substrate method) is proposed for coating calcium phosphates such as hydroxyapatite (HA), on titanium substrates in an aqueous solution. Several factors (e.g., the type of ion source, the heating time and temperature, and the surface roughness of the substrate) affected the characteristics of the precipitate formed by this method. The solution used included 3 mmol dm−3 Ca(H2PO4)2 and 7 mmol dm−3 CaCl2, and its pH was adjusted to 6.5. The experimental studies were conducted under the following conditions: temperature 45–160°C, heating time 10–20 min, and surface roughness of substrate #120–#2000 grid ground using energy paper. A high quality of precipitate, whose predominant component was HA, was obtained on titanium substrates by the thermal substrate method in an aqueous solution. No significant difference in the precipitates was found with the type of ion source. The amount of HA precipitate increased with increasing temperature and with increasing heating time. The features of the precipitate were different, depending on the surface roughtness of the substrate: HA regularly nucleated along the grooves of the rough surface (#120 and #400 grid), and in the case of the fine surface (#1200–#2000 grid), a uniform precipitation occurred. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 390–397, 2002
Adhesion between poly(ethylene‐co‐vinyl alcohol) (EVA) and titanium
Authors: Matsumura Kazuaki , Hyon Suong‐Hyu , Nakajima Naoki , Peng Chunyan , Iwata Hiroo , Tsutsumi Sadami
Published: August 2002

Lap shear adhesive strength between titanium and various kinds of commercial polymers was evaluated. Among them, poly(ethylene‐co‐vinyl alcohol) (EVA) showed the highest strength. The results of electron spectroscopy for chemical analysis and the contact angle to water indicated that the high adhesive strength of EVA might be due to its high hydrophilicity. Water resistance of adhesion by water immersing at 37°C was investigated. In the case of polyurethane‐titanium, the adhesive strength decreased immediately. In contrast, EVA‐titanium kept its initial adhesive strength for at least up to 1 month. It was confirmed that surface modification of titanium by hydrogen peroxide enhanced the adhesive and peeling strength. It was based on not only an increase in surface adhesive area but also an increase in the hydrophilicity of titanium by the production of Ti‐OH. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 309–315, 2002; DOI 10.1002/jbm.10051
Effect of surface treatment of NiTi alloy on its corrosion behavior in Hanks’ solution
Authors: Cissé O. , Savadogo O. , Wu M. , Yahia L'H.
Published: August 2002

The effect of surface modification of NiTi shape memory alloy on its corrosion behavior in Hanks’ solution was determined. The near‐equi‐atomic super elastic NiTi (Ni 55.8 wt %) alloy used for this study was provided by Memry USA. The surfaces of heat‐treated samples were modified by mechanical polishing (MP), electropolishing (EP), and electropolishing followed by chemical passivation (CP). As‐heat‐treated samples with straw‐colored oxide finishes (SCO) and blue‐colored oxide finishes (BO) also were included in the study. Surface analysis was performed using auger electron spectroscopy (AES), atomic force microscopy (AFM), and contact angle measurements (CAM). It was shown that surface roughness increased in the order CP < EP < SCO < BO < MP. The nickel release within the five groups of NiTi samples, as determined by atomic absorption spectrophotometry, reduced in time over the measured period. The level of Ni ions released over a 25‐day immersion period was highest in the SCO sample (0.002 μg/day). This Ni level is negligible compared with the daily intake of Ni in an ordinary diet. The auger electron spectroscopy (AES) analyses indicated that before immersion in Hanks’ physiologic solution, the main surface composition of all the samples was titanium and nickel, with a small amount of oxygen, carbon, and sulphur as contaminants. And the surface oxide thickness of the different samples increased in the order CP < EP < MP < BO < SCO. On the other hand, for the electrodes treated under the same conditions, the mean breakdown potential value decreased in the order BO > MP > CP > EP > SCO while the corrosion current density and rate increased in the order CP < SCO < EP < BO < MP. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 339–345, 2002
Application of frog (Rana tigerina Daudin) skin collagen as a novel substrate in cell culture
Authors: Kumar K. V. Sathya Sai , Sai K. Purna , Babu M.
Published: August 2002

Collagen and collagen‐based materials have extensive application in biomedical devices and tissue engineering. The current paper pertains to the application of frog (Rana tigerina Daudin) skin collagen as a novel substrate in cell culture. The study deals with the behavior, morphology, and physiology of keratinocytes and fibroblasts over dry and reconstituted collagen substratum, which are the key cells involved in wound repair. The advantage of using frog skin collagen as a substratum lies in the ease with which the reconstituted gel can be formed. Further, frog skin collagen is highly hydrophilic, which may be attributed to the fact that amphibians, as the first vertebrates connecting water and land, must have evolved certain physiologic specializations. These studies also contribute to the hypothesis that part of the healing efficacy of frog skin may be due to the collagen since proliferation, migration, and differentiation of epithelial cells are prime requisites for a normal healing mechanism. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 197–202, 2002
Ultimate tensile strength of dentin: Evidence for a damage mechanics approach to dentin failure
Authors: Staninec Michal , Marshall Grayson W. , Hilton Joan F. , Pashley David H. , Gansky Stuart A. , Marshall Sally J. , Kinney John H.
Published: August 2002

Dentin structure and properties are known to vary with orientation and location. The present study explored the variation in the ultimate tensile strength (UTS) of dentin with location in the tooth. Hourglass specimens were prepared from dentin located in the center, under cusps, and in the cervical regions of human molar teeth. These were tested in tension at various distances from the pulp. Median tensile strengths ranged from 44.4 MPa in the inner dentin near the pulp, to 97.8 MPa near the dentino–enamel junction (DEJ). This increase in the median UTS with distance from the pulp to the DEJ was statistically significant (P <.001). Of particular importance was the observation that the UTS measurements followed a Weibull probability distribution, with a Weibull modulus of about 4.5. The Weibull behavior of the UTS data strongly suggests that the large variances in fracture strength data result from a distribution of preexisting defects in the dentin. These findings justify a damage‐mechanics approach to studies of dentin failure. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 342–345, 2002
Transforming growth factor β released from natural coral implant enhances bone growth at calvarium of mature rat
Authors: Vuola Jyrki , Böhling Tom , Göransson Harry , Puolakkainen Pauli
Published: August 2002

Earlier studies have shown that transforming growth factor β (TGF‐β) has the capability of enhancing bone formation after a single application to an orthotopic site. We investigated whether 1, 5, or 25 μg of recombinant human TGF‐β1 added to porous natural coral (NC) blocks could promote bone ingrowth in a critical size defect (CSD) model in nongrowing rats. A 6‐mm CSD in the parietal bone of Wistar rats was filled with NC disks, which were retrieved at 3 and 8 weeks. We prepared undecalcified sections for microscopy and histomorphometry to study bone formation in the implants. The differences in the means of the measured variables were compared with a one‐way analysis of variance and Tukey's Student range test, and p values smaller than 0.05 were considered statistically significant. Bone formation was enhanced in all the TGF‐β1‐treated implants at 8 weeks in comparison with the controls, but none of the implants showed complete bridging across the defect. The number of macrophages and giant cells was reduced in the TGF‐β1 implants, which showed less resorption and more intact structure than the coral controls. Void areas without any fibrous tissue ingrowth were found only in the TGF‐β1‐treated implants, which may partly explain the reduced resorption. The data suggested that TGF‐β1 induced enhanced but limited bone formation in mature rats and prevented resorption of the coral calcium carbonate matrix, possibly by hindering reactive cell formation and fibrous tissue ingrowth. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 152–159, 2002
Mutagenicity evaluation of forty‐one metal salts by the umu test
Authors: Yamamoto Akiko , Kohyama Yuko , Hanawa Takao
Published: August 2002

Metallic biomaterials implanted in a human body may corrode and wear, releasing metal ions and debris which may induce adverse reactions such as inflammation, allergy, neoplastic formation, developmental malformation, etc. Mutagenicity is a very fundamental and important toxicity related to carcinogenicity and reproductive/developmental toxicity because the damages to genes or DNA can be a cause of carcinogenesis and developmental abnormalities. However, available mutagenic data on metallic ions and compounds are restricted to the number of elements. Therefore, to obtain the systematic data necessary for metal ion mutagenicity, 41 metal salts encompassing 36 metals and 5 metallic elements tested with different valences, were evaluated on their mutagenicity by a microbial test, the umu test. As a result, K2Cr2O7, RhCl3, IrCl4, and MgCl2 are positive without metabolic activation. Concentrations having the maximum mutagenic effect (Cmax) are 9.65 × 10−5, 1.00 × 10−4, 3.11 × 10−3, 4.12 × 10−3 mol · L−1, respectively. CuCl2, VCl3, CuCl, RhCl3, K2Cr2O7, and IrCl4 are positive with metabolic activation by S‐9 mix with Cmax of 1.60 × 10−5, 3.91 × 10−5, 1.57 × 10−4, 2.00 × 10−4, 3.86 × 10−4, 1.56 × 10−2 mol · L−1, respectively. Thirty‐five metal salts were negative for tests performed both with and without metabolic activation, whereas it was impossible to evaluate the mutagenicity of MoCl5 and ZrCl4 by the umu test because of their colorimetric reaction to testing reagents. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 176–183, 2002
Probe of specific interaction between a simplified synthetic glycopolymer and erythrocytes as mediated by a glucose transporter (GLUT) on a cell membrane
Authors: Park Keun‐Hong , Na Kun , Akaike Toshihiro , Lee Kang Choon
Published: August 2002

In order to develop a biomimetic polymer for cell recognition, we synthesized poly [3‐O‐(4′‐vinylbenzyl)‐D‐glucose] (PVG), a polystyrene derivative with reduced glucose moiety, and studied the specific interaction of this PVG with erythrocytes, carried by a glucose transporter (GLUT‐1), on a cell membrane. To clarify the specific interaction between the PVG and the erythrocytes, fluorescence isothiocyanate‐ (FITC) labeled polymer was used to prove and visualize the specific interaction. We found that labeled polymer strongly binds to erythrocytes, probably due to the specific interaction mediated by the presence of GLUT‐1 on the cell membrane. The fluorescence intensity of PVG on erythrocytes was time and dose dependent. To verify the specific interaction between the PVG and the erythrocytes, cells were pretreated with phloretin, an inhibitor of GLUT‐1, before adding the FITC‐labeled PVG polymer to the cell‐culture medium. This treatment suppressed the interaction of PVG with erythrocytes. A confocal laser microscopic study further confirmed this interaction. The results from this study provide evidence that a biomimetic polymer of PVG interacts with erythrocytes mediated by GLUT‐1 on cell membranes. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 591–594, 2002
Effects of quercetin on antioxidant defense in streptozotocin‐induced diabetic rats
Authors: Sanders Ruth A. , Rauscher Frederick M. , Watkins John B.
Published: August 2002

In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin‐induced diabetic Sprague‐Dawley rats (30 days after streptozotocin induction). Quercetin, 2‐(3,4‐dihydroxyphenyl)‐3,5,7‐trihydroxy‐4H‐1‐benzopyran‐4‐one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free‐radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:143–149, 2001
26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer
Authors: Shah Shimul A. , Potter Michael W. , McDade Theodore P. , Ricciardi Rocco , Perugini Richard A. , Elliott Peter J. , Adams Julian , Callery Mark P.
Published: August 2002

The 26S proteasome degrades proteins that regulate transcription factor activation, cell cycle progression, and apoptosis. In cancer, this may allow for uncontrolled cell division, promoting tumor growth, and spread. We examined whether selective inhibition of the 26S proteasome with PS‐341, a dipeptide boronic acid analogue, would block proliferation and induce apoptosis in human pancreatic cancer. Proteasome inhibition significantly blocked mitogen (FCS) induced proliferation of BxPC3 human pancreatic cancer cells in vitro, while arresting cell cycle progression and inducing apoptosis by 24 h. Accumulation of p21Cip1‐Waf‐1, a cyclin dependent kinase (CDK) inhibitor normally degraded by the 26S proteasome, occurred by 3 h and correlated with cell cycle arrest. When BxPC3 pancreatic cancer xenografts were established in athymic nu/nu mice, weekly administration of 1 mg/kg PS‐341 significantly inhibited tumor growth. Both cellular apoptosis and p21Cip1‐Waf‐1 protein levels were increased in PS‐341 treated xenografts. Inhibition of tumor xenograft growth was greatest (89%) when PS‐341 was combined with the tumoricidal agent CPT‐11. Combined CPT‐11/PS‐341 therapy, but not single agent therapy, yielded highly apoptotic tumors, significantly inhibited tumor cell proliferation, and blocked NF‐κB activation indicating this systemic therapy was effective at the cancer cell level. 26S proteasome inhibition may represent a new therapeutic approach against this highly resistant and lethal malignancy. J. Cell. Biochem. 82: 110–122, 2001. © 2001 Wiley‐Liss, Inc.
Possible involvement of protein kinase C in the induction of adipose differentiation‐related protein by Sterol ester in RAW 264.7 macrophages
Authors: Chen Jin‐Shan , Greenberg Andrew S. , Tseng Yung‐Zu , Wang Seu‐Mei
Published: August 2002

The accumulation of lipid droplets in macrophages contributes to the formation of foam cells, an early event in atherosclerosis. It is, therefore, important to elucidate the mechanisms by which lipid droplets accumulate and are utilized. Sterol ester (SE)‐laden RAW 264.7 macrophages accumulated lipid droplets in a time‐dependent manner up to 16 h, which was enhanced by cotreatment with 0.1 μM phorbol 12‐myristate 13‐acetate (PMA). Inhibition of protein kinase C (PKC) activity by cotreatment with 0.3 μM calphostin C CAL for 16 h resulted in coalescence of small lipid droplets into large ones and increased accumulation of lipid droplets, although to a lesser extent than after PMA cotreatment. Immunostaining for adipose differentiation‐related protein (ADRP) revealed a fluorescent rim at the surface of each medium to large lipid droplet. ADRP appearance correlated with lipid droplet accumulation and was regulated by PMA in a time‐dependent manner. Induction of ADRP expression by PMA or CAL required SE, since ADRP levels in PMA‐ or CAL‐treated non‐SE‐laden macrophages were comparable to those in untreated cells. Removal of SE from the incubation medium resulted in the concomitant dissolution of lipid droplets and down‐regulation of ADRP. In conclusion, the above results suggest that ADRP may be an important protein in the regulation of lipid droplet metabolism in lipid‐laden macrophages and that this regulation may be mediated by PKC activity. J. Cell. Biochem. 83: 187–199, 2001. © 2001 Wiley‐Liss, Inc.
Expression of different NF‐κB pathway genes in dendritic cells (DCs) or macrophages assessed by gene expression profiling
Authors: Baltathakis Ioannis , Alcantara Orlando , Boldt David H.
Published: August 2002

NF‐κB/Rel transcription factors have been implicated in the differentiation of monocytes to either dendritic cells (DCs) or macrophages, as well as in the maturation of DCs from antigen‐processing to antigen‐presenting cells. Recent studies of the expression pattern of Rel proteins and their inhibitors (IκBs) suggest that their regulation during this differentiation process is transcriptional. To investigate differential gene expression between macrophages and DCs, we used commercially available gene microarrays (GEArray KIT), which included four of the NF‐κB/Rel family genes (p50/p105, p52/p100, RelB, and c‐rel) and 32 additional genes either in the NF‐κB signal transduction pathway or under transcriptional control of NF‐κB/Rel factors. To generate macrophages and DCs, human adherent peripheral blood monocytes were cultured with M‐CSF or GM‐CSF + IL‐4 respectively for up to 8 days. DCs (and in some experiments, macrophages) were treated with lipopolysaccharide (LPS) for the last 48 h of culture to induce maturation. Cells were harvested after 7 days, cDNA was prepared and radiolabeled with α‐32P‐dCTP, then hybridized to gene arrays containing specific gene probes. β‐actin and GAPDH or PUC18 oligonucleotides served as positive or negative controls, respectively. The expression of all four NF‐κB/Rel family genes examined was significantly upregulated in maturing DCs compared to macrophages. The strongest difference was observed for c‐rel. RT‐PCR determinations of c‐rel, RelB, and p105 mRNAs confirmed these observations. Among the 32 NF‐κB/Rel pathway genes, 14 were upregulated in mature DCs compared to macrophages. These genes were IκBα, IKK‐β, NIK, ICAM‐1, P‐selectin, E‐selectin, TNF‐α, TNFR2, TNFAIP3, IL‐1α, IL‐1R1, IL‐1R2, IRAK, and TANK. By contrast, only mcp‐1 (monocyte chemotactic protein 1) was upregulated in macrophages compared to DCs. NF‐κB pathway genes upregulated in DCs compared to macrophages were constitutively expressed in monocytes then selectively downregulated during macrophage but not DC differentiation. LPS did not induce expression of most of these genes in macrophages but LPS did induce upregulation of IL‐8 in mature macrophages. We conclude that NF‐κB/Rel family genes, especially c‐rel, are selectively expressed during differentiation of monocytes towards DCs. Moreover, this differential expression is associated both with activation of different NF‐κB signal transduction pathways in DCs and macrophages and with expression of a unique subset of genes in DCs that are transcriptionally targeted by NF‐κB/Rel factors. The results illustrate the ability of the NF‐κB pathway to respond to differentiation stimuli by activating in a cell‐specific manner unique signalling pathways and subsets of NF‐κB target genes. J. Cell. Biochem. 83: 281–290, 2001. © 2001 Wiley‐Liss, Inc.