bluuebunny/crossref_metadata_2025 huggingface dataset:
PKC activation rescues LTP from NMDA receptor blockade
Authors: Kleschevnikov Alexander M. , Routtenberg Aryeh
Published: August 2002

It has been proposed that a critical step in long‐term potentiation (LTP) expression is the activation of presynaptic protein kinase C (PKC) after activation of postsynaptic NMDA receptors. A prediction from this “synaptic dialogue” hypothesis (Routtenberg, Trends Neurosci 1999;22:255–256) is that the well‐known blockade of LTP by NMDA receptor antagonists would be rescued by direct activation of PKC. To test this prediction we recorded extracellular EPSPs in the molecular layer of the dentate gyrus (DG) in the intact, anesthetized mouse after stimulation of the perforant path. Three experimental series were performed in which tetanization was applied after continuous infusion of 1) vehicle, 2) NMDA receptor antagonist dl‐2‐amino‐5‐phosphonovaleric acid (APV) (2.5 ± 1.0 nmol), or 3) both APV and then PKC activator 4‐beta‐phorbol‐12,13‐dibutyrate (PDBu, 9.0 ± 1.0 pmol). LTP was reliably induced in the first series (124 ± 5%, N = 6; 2.5 h after the tetanus), suppressed by APV in the second series (95 ± 18%, N = 4), and restored in the third series (121 ± 13%, N = 5). Decreased paired‐pulse facilitation, an index of presynaptic involvement in LTP expression, was observed after tetanization in the first and third series, but not in the second series. Blockade of LTP by NMDA receptor antagonists that can be overridden by presynaptic activation of PKC is thus consistent with the proposed hypothesis. As LTP is rescued after NMDA receptor blockade in transgenic mice overexpressing growth‐associated presynaptic protein GAP‐43, we suppose that this protein is one of the presynaptic targets of PKC activation. Hippocampus 2001;11:168–175. © 2001 Wiley‐Liss, Inc.
Hippocampal spatial representations require vestibular input
Authors: Stackman Robert W. , Clark Ann S. , Taube Jeffrey S.
Published: August 2002

The hippocampal formation is essential for forming declarative representations of the relationships among multiple stimuli. The rodent hippocampal formation, including the entorhinal cortex and subicular complex, is critical for spatial memory. Two classes of hippocampal neurons fire in relation to spatial features. Place cells collectively map spatial locations, with each cell firing only when the animal occupies that cell's “place field,” a particular subregion of the larger environment. Head direction (HD) cells encode directional heading, with each HD cell firing when the rat's head is oriented in that cell's particular “preferred firing direction.” Both landmarks and internal cues (e.g., vestibular, motor efference copy) influence place and HD cell activity. However, as is the case for navigation, landmarks are believed to exert greater influence over place and HD cell activity. Here we show that temporary inactivation of the vestibular system led to the disruption of location‐specific firing in hippocampal place cells and direction‐specific discharge of postsubicular HD cells, without altering motor function. Place and HD cell activity recovered over a time course similar to that of the restoration of vestibular function. These results indicate that vestibular signals provide an important influence over the expression of hippocampal spatial representations, and may explain the navigational deficits of humans with vestibular dysfunction. Hippocampus 2002;12:291–303. © 2002 Wiley‐Liss, Inc.
Patient referral patterns in Namibia: identification of potential to improve the efficiency of the health care system
Authors: Low Anne , Coeyere Dirk de , Shivute Nestor , Brandt Laura J.
Published: August 2002

In order to assess how the hospital referral system in Namibia was operating, a cross‐sectional survey of patients attending three intermediate hospitals and the national hospital was conducted over a 4‐week period. The survey was planned by a Ministry of Health and Social Services' working group, with technical support provided by a donor funded health programme. Together with complementary qualitative data, obtained through focus group discussions with the community, the survey generated information on the extent to which the referral system was being bypassed, the types of bypassing and related factors. These included reasons for non‐compliance with referral to the intermediate hospitals, perceived barriers to their utilization and community preparedness to use these hospitals after upgrading. The results were used to inform decisions about the classification of the three hospitals and identification of their catchment areas. The results were also shown to be useful for assessing the likely impact of different strategies for reducing bypassing. In Namibia these impacts were expected to be limited, due to the influence of distance and low population densities. Information on the extent and types of bypassing taking place across districts is essential for assessing opportunities to improve the functioning of a pyramidal referral system, which supports a cost‐effective primary health care strategy. Copyright © 2001 John Wiley & Sons, Ltd.
A perspective adjustment to add value to external clients, including society
Authors: Kaufman Roger , Guerra Ingrid
Published: August 2002

Our realities have shifted. What was comfortable and acceptable will no longer provide useful guidance on
what any HRD professional uses, does, and delivers. There is a new and overriding focus on external value added
for both clients and society. This article gives the rationale and guidance on what it takes to adjust our
perspectives in order to define and deliver success. And prove it.
Measurement of mutual diffusion coefficients of gases by the Taylor method: Measurements on H2–Air,H2–N2, and H2–O2 systems
Authors: Matsunaga Naoki , Hori Morio , Nagashima Akira
Published: August 2002

Mutual diffusion coefficients of hydrogen gas (H2) into air and its component gases (N2 and O2) have been measured in the temperature range of 30 to 180°C and at atmospheric pressure via the Taylor dispersion method. For a H2–N2 system, the composition dependence of the mutual diffusion coefficient has been studied with both H2 and N2 as the carrier gas. The mutual diffusion coefficients for the H2–air and H2–N2 systems are almost the same and smaller than that for the H2–O2 system by about 5%. The present data for the H2–N2 system, corrected to an equimolar composition, agree well with the accurate data reported by the groups of P. J. Dunlop and of R. J. J. Van Heijningen. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(3): 182–193, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10025
Auditory verbal learning in drug‐free Ecstasy polydrug users
Authors: Fox H. C. , Toplis A. S. , Turner J. J. D. , Parrott A. C.
Published: August 2002

Drug‐free Ecstasy polydrug users have shown impairment on tasks of verbal working memory and memory span. Current research aims to investigate how these deficits may affect the learning of verbal material by administration of the Auditory Verbal Learning Task (AVLT) (Rey, 1964). The task provides a learning curve by assessing immediate memory span over multiple trials. Learning strategies are further analysed by tendencies to confabulate as well as demonstrate either proactive or retroactive interference elicited by a novel ‘distractor’ list. Three groups completed the task: two groups of 14 Ecstasy users (short‐ and long‐term) and one group of 14 polydrug controls. Compared with controls both Ecstasy groups recalled significantly fewer words and made more confabulation errors on the initial three recall trials as well as a delayed recall trial. Long‐term users demonstrated increased confabulation on the initial trials and the novel ‘distractor7’ trial, compared with short‐term users. Only following repeated presentations were both short‐ and long‐term users shown to perform at control levels. As such, deficits in verbal learning may be more related to storage and/or retrieval problems than problems associated with capacity per se. No interference errors were demonstrated by either of the Ecstasy groups. However, a high level of intrusion errors may indicate selective working memory problems associated with longer‐term use of the drug. Copyright © 2001 John Wiley & Sons, Ltd.
The distribution and strength of riparian tree roots in relation to riverbank reinforcement
Authors: Abernethy Bruce , Rutherfurd Ian D.
Published: August 2002

The main influences of plants on the mass stability of riverbanks are those that affect the strength of bank sediments. Plants enhance bank strength by reducing pore‐water pressures and by directly reinforcing bank material with their roots. In this paper we do not consider bank hydrology but focus on quantifying increases in sediment strength due to root reinforcement. Root reinforcement is a function of root strength, interface friction between the roots and the soil, and the distribution of roots within the soil. Field and laboratory studies of Australian riparian trees, river red gum (Eucalyptus camaldulensis) and swamp paperbark (Melaleuca ericifolia), indicate that bank reinforcement, due to the roots of these species, decreases exponentially with depth below the soil surface and distance away from the trees. Differences in the spatial distribution of root reinforcement are illustrated by a comparison of the apparent cohesion due to roots (cr) with the effective cohesion of the saturated bank material (15 kPa). Directly below the river red gum, root reinforcement is equal to effective cohesion at 1·7 m depth. At the dripline (17 m from the trunk), root reinforcement is equal to material strength at 0·4 m depth. For the swamp paperbark, cr=15 kPa at 1·1 m depth beneath surface, at the trunks, and at 0·4 m depth at the dripline (2·5 m from the trunk). A description of the spatial distribution of root reinforcement is important in the riverbank context. We find that interspecies differences in the strength of living roots have less significance for bank reinforcement than interspecies differences in root distribution. Copyright © 2001 John Wiley & Sons, Ltd.
Qualitative methods in the study of children's racial attitudes and identities
Authors: Connolly Paul
Published: August 2002

This article examines the role that qualitative methods can play in the study of children's racial attitudes and identities. It does this by discussing a number of examples taken from a qualitative, ethnographic study of 5‐ and 6‐year‐old children in an English multi‐ethnic, inner‐city primary school. The examples are used to highlight the limitations of research that relies solely on quantitative methods and the potential that qualitative methods have for addressing these limitations. Within this context, the article contrasts the strengths and weaknesses of qualitative and quantitative methods in the study of children's racial attitudes and identities. The article concludes by arguing that a much more integrated, multi‐method approach is needed in this area and sets out some of the most effective ways this could be achieved. Copyright © 2001 John Wiley & Sons, Ltd.
Executive control and higher‐order theory of mind in children at risk of ADHD
Authors: Perner Josef , Kain Winfried , Barchfeld Petra
Published: August 2002

Nursery teachers assessed 234 children aged 4½ to 6½ years on the DSM‐IV criteria for hyperactivity–impulsivity and attention deficit (ADHD). Using slightly lenient classification criteria 21 children scored on hyperactivity–impulsivity and/or attention deficit and were classified as ‘at risk of ADHD’. An age‐matched control group showed significant relations between acquisition of an advanced theory of mind, in particular understanding second‐order beliefs, and executive competence as measured by several tasks from the NEPSY. This extends findings from younger children that theory of mind development relates to executive control. The group at risk of ADHD showed impaired performance relative to the control group on several executive tasks but no impairment at all on the advanced theory of mind tasks. This speaks against the theory that later theory of mind development is a consequence of improvements in executive control. Copyright © 2002 John Wiley & Sons, Ltd.
Topotecan inhibits VEGF‐ and bFGF‐induced vascular endothelial cell migration via downregulation of the PI3K‐Akt signaling pathway
Authors: Nakashio Ayako , Fujita Naoya , Tsuruo Takashi
Published: August 2002

Angiogenesis plays a crucial role in tumor growth and metastases. The extent of angiogenesis correlates with the increased invasion and metastasis in a variety of human neoplasms. Vascular endothelial cell proliferation and migration are critical steps in angiogenesis and are regulated by various growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The topoisomerase I inhibitor topotecan (10‐hydroxy‐9‐dimethylaminomethyl‐(S)‐camptothecin) is a water‐soluble camptothecin analogue and possesses an indirect in vivo antitumor effect mediated through the inhibition of angiogenesis. We found that topotecan inhibited VEGF‐ and bFGF‐induced migration of human umbilical vein endothelial cells (HUVECs) in vitro. The migration of HUVECs was also inhibited by a phosphatidylinositol 3‐kinase (PI3K) inhibitor, LY294002. Thus, we investigated the possibility that topotecan's antiangiogenic property might be mediated by its inhibitory effect on VEGF‐ and bFGF‐induced activation of the PI3K‐Akt signaling pathway. We found that topotecan treatment decreased the amount of the phosphorylated (activated) form of Akt, but not the amount of Akt protein, in HUVECs. Moreover, transient transfection of constitutive active akt cDNA into HUVECs reversed the topotecan‐mediated decrease in HUVEC migration. These results suggest that the antiangiogenic activity of topotecan is mediated in part by downregulating the PI3K‐Akt signaling pathway. © 2001 Wiley‐Liss, Inc.
Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish family‐cancer database
Authors: Czene Kamila , Lichtenstein Paul , Hemminki Kari
Published: August 2002

The genetic and environmental components in 15 common cancers were estimated using the nationwide Swedish Family‐Cancer Database. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modeling was used to derive estimates of the importance of genetic and environmental effects. Statistically significant estimates of proportion of cancer susceptibility, accounted for by genetic effects, were obtained for all studied cancers except for leukemia. The estimate was highest in thyroid cancer (53%), followed by tumors at endocrine glands (28%), testis (25%), breast (25%), cervix (22%), melanoma (21%), colon (13%), nervous system (12%), rectum (12%), non‐Hodgkin lymphoma (10%), lung (8%), kidney (8%), urinary bladder (7%), stomach (1%) and leukemia (1%). The estimates of shared environmental effects ranged from 0% (cervix) to 15% (stomach). The childhood shared environmental effects were most important in testicular cancer (17%), stomach cancer (13%) and cervix in situ (13%). Our results indicate that environment has a principal causative role in cancer at all studied sites except for thyroid. The relatively large effect of heritability in cancer at some sites, on the other hand, indicates that even though susceptibility genes have been described at many cancer sites, they are likely to explain only part of the genetic effects. © 2002 Wiley‐Liss, Inc.
Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF‐κB and AP‐1 activation and IL‐8 and VEGF expression in human head and neck squamous cell carcinoma lines
Authors: Bancroft Caren C. , Chen Zhong , Yeh Jason , Sunwoo John B. , Yeh Ning T. , Jackson Sadhana , Jackson Chad , Van Waes Carter
Published: August 2002

We previously reported that expression of angiogenesis factors interleukin‐8 (IL‐8) and vascular endothelial growth factor (VEGF) is promoted by coactivation of transcription factors nuclear factor‐kappaB (NF‐κB) and activator protein‐1 (AP‐1) by interleukin‐1α in human head and neck squamous cell carcinomas (HNSCC). However, expression of IL‐1 receptor antagonist incompletely blocked reporter gene activity and cytokine expression, suggesting that other upstream signals may contribute to activation. Overexpression and autocrine activation of epidermal growth factor receptor (EGFR) is detected in 90% of HNSCC, and EGFR inhibitors have been reported to inhibit IL‐8 and VEGF expression, but the intermediary signal pathways and transcription factors by which EGFR modulates proangiogenic factors is unknown. EGFR can activate the phosphotidylinositol‐3 kinase (PI3K) and mitogen‐activated/extracellular signal‐regulated kinase (MEK) pathways, which can potentially modulate activation of NF‐κB and AP‐1, respectively. In our study, we examined the effect of EGF and antagonists of EGFR, PI3K and MEK on NF‐κB and AP‐1 activation and IL‐8 and VEGF expression in HNSCC cell lines UM‐SCC‐9 and 11B in which EGFR is overexpressed and activated. Recombinant EGF induced EGFR phosphorylation, activation of NF‐κB and AP‐1 reporter genes and IL‐8 and VEGF expression, indicating that EGFR can mediate coactivation of both transcription factors and cytokine genes in HNSCC. EGFR antagonist PD153035 and anti‐EGFR antibody C225 completely inhibited EGF‐induced reporter activity and cytokine expression, but only partially inhibited constitutive activity. MEK inhibitor U0126 preferentially blocked AP‐1 activity and expression of both IL‐8 and VEGF, while PI3K inhibitor LY‐294002 or a dominant negative inhibitor‐κB preferentially blocked NF‐κB activation and expression of IL‐8 but not VEGF. EGFR, PI3K and MEK antagonists inhibited growth of HNSCC. We conclude that antagonists of EGFR, PI3K and MEK signal pathways have inhibitory activity against EGFR‐induced NF‐κB and AP‐1 activation, IL‐8 and VEGF expression and growth by HNSCC. Published 2002 Wiley‐Liss, Inc.
Characterization of XAGE‐1b, a short major transcript of cancer/testis‐associated gene XAGE‐1, induced in melanoma metastasis
Authors: Zendman Albert J.W. , van Kraats Annemieke A. , den Hollander Anneke I. , Weidle Ulrich H. , Ruiter Dirk J. , van Muijen Goos N.P.
Published: August 2002

Suppression subtractive hybridization, comparing mRNA expression profiles of common nevocellular nevi and melanoma metastases, was used to identify potential markers of melanoma progression. From the metastases we isolated XAGE‐1b, a 470 bp transcript of the XAGE‐1 gene. In general, expression of XAGE‐1b was much more prominent than expression of the longer XAGE‐1 transcript, isolated from Ewing's sarcoma. The XAGE‐1b open‐reading frame codes for a putative protein of 81 amino acids, harboring a functional bipartite nuclear localization signal and a C‐terminal acidic transcription‐activation‐like domain. On the nucleotide level, XAGE‐1b has a 50% homology with members of the GAGE family. However, homology between the corresponding proteins is weak. Expression of XAGE‐1b in normal tissues was mainly restricted to testis, while placenta and brain were sporadically positive. In human tumor cell lines as well as in human tumor lesions, expression was most frequently found in melanocytic tumors and Ewing's sarcoma. In the different stages of melanocytic tumor progression, expression was exclusively seen in melanoma metastases (38%; n = 61), while all tested common and atypical nevi (n = 10) as well as primary melanomas (n = 8) were negative. Upregulation of expression after treatment with demethylating agent 5‐aza‐2′‐deoxycytidine was detected in 1 of 4 human melanoma cell lines tested. The XAGE‐1 gene consists of 4 exons and is located on chromosome Xp11.21–Xp11.22. After transfection into COS cells, the corresponding protein can direct the coupled fluorescent protein to the nucleus, showing a distinct speckled staining aspect. Our data imply the nuclear cancer/testis‐associated XAGE‐1b to be a marker for late melanocytic tumor progression. © 2002 Wiley‐Liss, Inc.
Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy
Authors: Lu Dan , Jimenez Xenia , Zhang Haifan , Bohlen Peter , Witte Larry , Zhu Zhenping
Published: August 2002

Compelling evidence suggests that vascular endothelial growth factor (VEGF) and its receptors play an important role in angiogenesis associated with tumor growth and metastasis. VEGF exerts its biologic activities through 2 transmembrane tyrosine kinase receptors: the fms‐like tyrosine kinase receptor (Flt‐1, or VEGFR1) and kinase insert domain‐containing receptor (KDR or VEGFR2). We have previously produced a panel of antibodies directed against KDR from mice immunized with the recombinant form receptor. These antibodies efficiently neutralized VEGF‐induced KDR activation and mitogenesis of human umbilical vascular endothelial cells (HUVEC). Murine antibodies, however, may not be suitable candidates for human therapy because of their propensity to elicit human anti‐mouse antibody response. Here we isolated several high‐affinity human Fab antibody fragments directed against KDR from an antibody phage display library constructed from the pooled B lymphocytes of nonimmunized healthy human donors. These human Fab fragments bind specifically to KDR with nanomolar affinity and block KDR/VEGF interaction with IC50 of approximately 2–20 nM. Further, they effectively inhibit VEGF‐stimulated mitogenesis of HUVEC and migration of human leukemia cells. Epitope mapping studies demonstrated that all neutralizing human antibodies bound the epitope(s) located within the first 3 N‐terminal immunoglobulin‐like domains of KDR, the same region that encompasses the binding site of VEGF. Our results suggest that these human anti‐KDR antibodies may have potential application in the treatment of cancer and other diseases in which pathologic angiogenesis occurs. © 2002 Wiley‐Liss, Inc.
Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk
Authors: Zavras Athanasios I. , Wu Tianxia , Laskaris George , Wang Yue‐Fen , Cartsos Vassiliki , Segas John , Lefantzis Dimitris , Joshipura Kaumudi , Douglass Chester W. , Diehl Scott R.
Published: August 2002

We investigated effects on oral cancer (OC) risk of an interaction between a single nucleotide polymorphism (SNP) in the alcohol dehydrogenase 3 (ADH3) gene and alcohol consumption levels using a hospital‐based study of 93 cases and 99 controls conducted in Athens, Greece. This SNP affects ethanol metabolism in vitro and appeared to interact with alcohol consumption in a previous OC study. We also evaluated a SNP in CYP2E1, another gene involved in ethanol metabolism, reported to be associated with OC risk in a European population. Data on genotypes and risk factors obtained from interviews were analyzed using multivariate logistic regression, accounting for potential confounders. No overall (marginal) association was found between OC risk and ADH3 genotypes. An interaction between ADH3 genotypes and alcohol consumption levels, however, was suggested. In non‐drinkers, the ADH31‐1 genotype has higher risk than ADH31‐2 or ADH32‐2 genotypes, but for subjects consuming alcohol, lower risk was observed for ADH3 We fit a logistic regression model to estimate the increase in OC risk associated with each alcohol drink consumed per week. We estimated that OC risk increased by 31.5% per drink/week for the ADH32‐2 genotype, 4.1% for the ADH31‐2 genotype and 1.6% for the ADH31‐1 genotype. Evidence of genotype‐environment interaction was suggestive (p = 0.048, Wald χ p = 0.145, likelihood ratio). This finding is opposite to that reported for a population in Puerto Rico, where the ADH31‐1 genotype seemed more sensitive to ethanol exposure. In Greece, genetic variation at the CYP2E1 SNP is almost entirely absent, with only 1 case and 1 control heterozygous for the variant. By contrast, in a population in France where an OC association was reported, the frequency of CYP2E1 heterozygotes was 5% in controls and 9% in OC cases. These findings illustrate the importance of replicating SNP associations both within and between different racial and ethnic groups and geographic regions. Published 2001 Wiley‐Liss, Inc.
Importance of technical and fundamental analysis in the European foreign exchange market
Authors: Oberlechner Thomas
Published: August 2002

This article presents findings of a questionnaire and an interview survey on the perceived importance of chartist/technical and fundamental analysis among foreign exchange traders and financial journalists in Frankfurt, London, Vienna, and Zurich. Results confirm that most traders use both forecasting approaches, and that the shorter the forecasting horizon, the more important chartist/technical analysis is. Financial journalists put more emphasis on fundamental analysis than do foreign exchange traders. Results indicate that the importance of chartism may have increased over the last decade. Regarding the use of chartist/technical and fundamental analysis on seven forecasting horizons, four distinct clusters of traders can be identified. Forecasting styles and the overall importance attached to fundamental versus chartist/technical analysis vary across different trading locations. Foreign exchange traders mention a series of psychological motives and consequences of the use of chartism. Copyright © 2001 John Wiley & Sons, Ltd.
In search of the ‘urban penalty’: exploring urban and rural mortality patterns in Spain during the demographic transition
Authors: Reher David S.
Published: August 2002

Making use of data on age‐specific mortality and cause of death patterns for rural and urban areas of Spain during the first third of the twentieth‐century, this paper explores the meaning of the ‘urban penalty’ and how it changed over the course of the demographic transition. The author finds ample proof of the existence of this penalty, especially visible among adult males in urban areas, where respiratory and other diseases, many of which were related to urban environments and lifestyles, took their toll on people's health. Despite these disadvantages, mortality decline, for the most part, was also much faster in towns than in the countryside. The author suggests that both the existence of the ‘urban penalty’ and the pioneering role of towns for mortality decline can best be understood in terms of the nature of towns and of urban life, society and government. Copyright © 2001 John Wiley & Sons, Ltd.
What future for whites? Population projections and racialised imaginaries in the US
Authors: Ellis Mark
Published: August 2002

Population projections forecast that the US will have a white minority by the middle of this century. This paper argues that changes in racial and ethnic categorisation, most notably the creation of the Hispanic category in 1977, have accelerated the projection of this date. These uncertainties illustrate a larger problem of projections of the future size of the white population: how can we know who will be white in the future if the criteria for whiteness shift as they have done in the past? It is possible, for example, that regions of immigration may see new forms of whiteness — or non‐blackness — as whites, Asians and Latinos hybridise into a new dominant group whose members will be advantaged relative to a black ‘other’. In the light of past modifications in racial constructions, and the potential for change in the future, why bother to project the populations of today's racial categories? The paper attempts to answer this question by reviewing the history of the practice of racial population projection. What this reveals is that racial population projections can be thought of as ‘racial projects’ — efforts to frame and thereby influence the racial future through the imposition of contemporary racial categories and meanings. Although this racial imagining has important consequences for contemporary political action, it is not politics alone that motivates projections by race. Other motivations include the mundane practices of categorisation and counting by race — racial governmentality — that make racial population projections possible to begin with. Copyright © 2001 John Wiley & Sons, Ltd.
A pediatric screening instrument to detect problematic infant–parent interactions: Initial reliability and validity in a sample of high‐ and low‐risk infants
Authors: Fiese Barbara H. , Poehlmann Julie , Irwin Martin , Gordon Michael , Curry‐Bleggi Ellen
Published: August 2002

The purpose of this study was to determine the initial reliability and validity of a screening instrument developed to detect problematic interactions between infants and parents as part of a pediatric well‐baby exam. Participants included 117 infant–mother dyads (57 preterms and 60 full terms) assessed when infants were 6 to 9 months old. Mothers and infants were observed playing an interactional game such as peek‐a‐boo during the course of the pediatric exam. The game was scored for degree of interactional reciprocity using the Pediatric Infant Parent Exam (PIPE). Acceptable levels of interrater reliability were achieved. As predicted, higher risk infants and their mothers exhibited more problematic interactions than lower risk infants and their mothers. Results indicated that the PIPE was a reliable means of screening for interactional difficulties, that was sensitive to, but not synonymous with, neonatal health indices. ©2001 Michigan Association for Infant Mental Health.
Compared effects of morphine and nickel chloride on NK cell activity in vitro in rats and monkeys
Authors: Condevaux Fabienne , Guichard Jocelyne , Forichon André , Aujoulat Michel , Descotes Jacques
Published: August 2002

The measurement of natural killer (NK) cell activity often is recommended as an endpoint for inclusion in the non‐clinical immunotoxicity evaluation of environmental chemicals and pharmaceuticals. To date, most data on the impact of immunotoxicants on NK cell activity have been obtained in the rat. Because non‐human primates often are used in the safety evaluation of new medicinal products, there is a need to compare chemically induced changes in NK cell activity between rats and primates. In this study, the in vitro effects of nickel chloride and morphine hydrochloride were investigated on NK cell activity in the rat and the cynomolgus monkey. Despite some species‐specific differences in the techniques used, rather similar results were obtained in the two species. At the higher concentration, nickel chloride induced a significant decrease in NK cell activity in the ranges of 21.6–24.3% (rat) and 34.4–42.2% (monkey), depending on the effector‐to‐target cell ratio used, and morphine hydrochloride induced a decrease in the ranges of 23.7–34.7% (rat) and 59.1–68.0% (monkey). These results suggest that NK cell activity can be used as a reliable endpoint for the assessment of immune effects during safety evaluation studies in the cynomolgus monkey. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of short‐term high‐dose and low‐dose dermal exposure to Jet A, JP‐8 and JP‐8 + 100 jet fuels
Authors: Monteiro‐Riviere Nancy , Inman Alfred , Riviere Jim
Published: August 2002

Occupational and environmental exposures to jet fuel recently have become a source of public and regulatory concern. This study investigates the cutaneous toxicity of three fuels used in both civilian and military aircraft. Pigs, an accepted animal model for human skin, were exposed to low‐dose (25 µl or 7.96 µl cm−2) or high‐dose (335 µl or 67 µl cm−2) Jet A, JP‐8 and JP‐8 + 100 under occluded (Hill Top® chamber or cotton fabric) and non‐occluded conditions for 5 h, 24 h and 5 days. To mimic occupational exposure, fuel‐soaked fabric (high dose) was used. Erythema, edema, transepidermal water loss (TEWL) and epidermal thickness were quantified. High‐dose fabric occluded sites had slight erythema at 5 h with increased erythema at 5 days. No erythema was noted in any of the occluded (Hill Top) or non‐occluded sites at any of the time points. Morphological assessments depicted slight intracellular epidermal edema at all time points. An increase in change in TEWL (ΔTEWL) was observed at the 5‐h and 24‐h fabric and Hill Top occluded treatments and a decrease at the 5‐day fabric and Hill Top occluded sites. In all 5‐day JP‐8 + 100 fabric sites, intracorneal microabscesses filled with inflammatory cells were observed. Epidermal thickening was significant (P < 0.05) in all three jet fuels at the high‐dose fabric sites, with JP‐8 + 100 being the thickest. The epidermal rete peg depth increased significantly (P < 0.05) at 24 h and 5 days with Jet A, JP‐8, and JP‐8 + 100 in the fabric sites. No significant differences were noted in the 5‐day non‐occluded fabric and Hill Top occluded and non‐occluded sites. Jet fuel JP‐8 + 100 tended to have the greatest proliferative response. In conclusion, the high‐dose fabric‐soaked exposure at 5 days to Jet A, JP‐8 and JP‐8 + 100 fuels caused the greatest increase in cutaneous erythema, edema, epidermal thickness and rete peg depth compared with high‐dose non‐occluded or low‐dose exposure under Hill Top occluded and non‐occluded conditions. Copyright © 2001 John Wiley & Sons, Ltd.
Synthesis, degradation, and in vitro cell responses of sodium phosphate glasses for craniofacial bone repair
Authors: Gough J. E. , Christian P. , Scotchford C. A. , Rudd C. D. , Jones I. A.
Published: August 2002

This report outlines the initial synthesis, degradation, and short‐term biocompatibility of sodium phosphate glasses, for use in the drawing of fibers and manufacture of biodegradable composites. Biocompatibility studies were performed using a macrophage cell line and primary human craniofacial osteoblasts. Sodium hydrogen phosphate and sodium dihydrogen phosphate glass synthesized for less than 1 h, resulted in a higher degradation rate than glass synthesized for 3 h or more (0.015 mg cm−2 h−1). Glasses with high and low ratios of hydrogen phosphate to dihydrogen phosphate had very similar degradation rates. A condensation route for the formation of the glass should give rise to varying degradation rates with varying ratios of starting materials. It is suggested that the degradation rate of the glass is independent of the concentrations of the initial reagents and that ring‐opening polymerization, which reaches an equilibrium state, occurs. Biocompatibility studies suggest minimal macrophage activation (low levels of peroxide and interleukin‐1β release and rounded morphology) and high osteoblast biocompatibility. The ultimate aim of our studies is to produce a biocompatible soluble phosphate glass that can be drawn into fibers for incorporation into a polycaprolactone matrix for craniofacial bone repair. This report demonstrates the successful production of a soluble glass, which is biocompatible with regard to osteoblasts and macrophages. Recent data from our laboratory have demonstrated successful fiber drawing and production of a novel polycaprolactone. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 481–489, 2002
Fabrication of porous biodegradable polymer scaffolds using a solvent merging/particulate leaching method
Authors: Liao Chun‐Jen , Chen Chin‐Fu , Chen Jui‐Hsiang , Chiang Shu‐Fung , Lin Yu‐Ju , Chang Ken‐Yuan
Published: August 2002

This study developed a solvent merging/par‐ ticulate leaching method for preparing three‐dimensional porous scaffolds. Poly(L‐lactic‐co‐glycolic acid) (PLGA) and sodium chloride particles were dry‐mixed and cast into a special mold, through which a liquid could pass due to a pressure difference. An organic solvent was then poured into the mold to dissolve and merge the PLGA particles under negative pressure. A nonsolvent was conducted into the PLGA/salt composite to solidify and precipitate the merged PLGA matrix. Finally, a large amount of water was passed through the mold to leach out the salt particles so as to create a porous structure. The results revealed that a highly porous three‐dimensional scaffold (>85 vol %) with a well interconnected porous structure could be achieved by this process. Porosity and the pore size of the scaffold were controlled using the ratio and the particle size of the added salt particles. A larger‐volume scaffold was produced using a larger mold. This work provides a continuous and simple procedure for fabricating a bulk three‐dimensional porous scaffold for tissue engineering. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 676–681, 2002
Effect of sodium content on the crystallization behavior of fluoramphibole glass–ceramics
Authors: Denry I. L. , Holloway J. A.
Published: August 2002

The purpose of this study was to evaluate the effect of sodium content on the crystallization behavior of glass–ceramics in the system SiO2‐MgO‐CaO‐Na2O‐K2O‐F. Five glass compositions were prepared with increasing sodium content. The compositions were melted at 1400 °C for 2 h and cast into 60 × 12‐mm ingots. Differential thermal analyses were performed on the glasses up to 1400 °C. Discs (1.5 × 12 mm) were cut from the ingots, nucleated in the temperature range 600–650 °C for 1–2 h, and crystallized in the temperature range 900–1000 °C for 0.5–4 h. The crystalline phases were analyzed by x‐ray diffraction. The microstructure was investigated by scanning electron microscopy. Differential thermal analyses showed that the crystallization exotherm occurred in the temperature range 600–750 °C. There was a linear relationship between the amount of sodium and the transformation temperatures. X‐ray diffraction revealed the presence of mica and diopside as major crystalline phases in the sodium‐free composition. Mica, diopside, and fluorrichterite were present in all other glass–ceramics. The microstructure of the sodium‐free glass–ceramic was characterized by the presence of hexagonal mica crystals and prismatic diopside crystals. All other compositions exhibited needle‐shaped fluorrichterite crystals (2–5 μm in length) in addition to mica and diopside crystals. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 48–52, 2002
Engineering vascular networks in porous polymer matrices
Authors: Peters Martin C. , Polverini Peter J. , Mooney David J.
Published: August 2002

Enhanced vascularization is critical to the treatment of ischemic tissues and the engineering of new tissues and organs. We have investigated whether sustained and localized delivery of vascular endothelial growth factor (VEGF) combined with transplantation of human microvascular endothelial cells (HMVECs) can be used to engineer new vascular networks. VEGF was incorporated and released in a sustained manner from porous poly(lactic‐co‐glycolic acid) (PLG) matrices to promote angiogenesis at the transplantation site. VEGF could be incorporated and released in a biologically active form from PLG matrices, with the majority of VEGF release (64%) occurring within 2 weeks. These matrices promoted a 260% increase in the density of host SCID mouse‐derived capillaries invading the matrices after 7 days of implantation, confirming the activity of the released VEGF. HMVECs were transplanted into SCID mice on PLG matrices, and organized to form immature human‐derived vessels within 3 days. Functional vessels were observed within 7 days. Importantly, when HMVECs were transplanted on VEGF‐releasing matrices, a 160% increase in the density of human‐derived blood vessels was observed after 14 days. These findings suggest that combining elements of vasculogenesis and angiogenesis provides a viable and novel approach to enhancing local vascularization. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 668–678, 2002
Application of magnetic resonance microscopy to tissue engineering: A polylactide model
Authors: Burg K. J. L. , Delnomdedieu M. , Beiler R. J. , Culberson C. R. , Greene K. G. , Halberstadt C. R. , Holder W. D. , Loebsack A. B. , Roland W. D. , Johnson G. A.
Published: August 2002

Absorbable polymers are unique materials that find application as temporary scaffolds in tissue engineering. They are often extremely sensitive to histological processing and, for this reason, studying fragile, tissue‐engineered constructs before implantation can be quite difficult. This research investigates the use of noninvasive imaging using magnetic resonance microscopy (MRM) as a tool to enhance the assessment of these cellular constructs. A series of cellular, polylactide constructs was developed and analyzed using a battery of tests, including MRM. Distribution of rat aortic smooth muscle cells within the scaffolds was compared as one example of a tissue engineering MRM application. Cells were loaded in varying amounts using static and dynamic methods. It was found that the cellular component was readily identified and the polymer microstructure readily assessed. Specifically, the MRM results showed a heterogeneous distribution of cells due to static loading and a homogenous distribution associated with dynamic loading, results that were not visible through biochemical tests, scanning electron microscopy, or histological evaluation independently. MRM also allowed differentiation between different levels of cellular loading. The current state of MRM is such that it is extremely useful in the refinement of polymer processing and cell seeding methods. This method has the potential, with technological advances, to be of future use in the characterization of cell–polymer interactions. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 380–390, 2002
Control of in vivo microvessel ingrowth by modulation of biomaterial local architecture and chemistry
Authors: Sanders J. E. , Baker A. B. , Golledge S. L.
Published: August 2002

We developed a method for controlling local architecture and chemistry simultaneously in biomaterial implants to control microvessel ingrowth in vivo. Porous polypropylene disks (5 mm in diameter and 40 μm thick) were plasma‐coated with a fluoropolymer and then laser‐drilled with 50‐μm‐diameter holes through their thickness. We then oxidized the disks to create hydroxyl functionality on the exposed polypropylene (inside the holes). Acrylamide was grafted to the hydroxyl groups through polymerization in the presence of activating ceric ions. Staining with toluidine blue O demonstrated that grafting occurred only inside the holes. We used the Hoffman degradation reaction to convert the amide groups of acrylamide to amine groups, and then we used ethylene glycol diglycidyl ether to attach biomolecules of interest inside the holes: secreted protein acidic and rich in cysteine (SPARC) peptide Lys‐Gly‐His‐Lys (KGHK; angiogenic), thrombospondin‐2 (TSP; antiangiogenic), or albumin (rat; neutral). In vivo testing in a rat subcutaneous dorsum model for a 3‐week interval demonstrated a greater vessel surface area (p = 0.032) and a greater number of vessels (p = 0.043) in tissue local to the holes with KGHK‐immobilized disks than with TSP‐immobilized disks. However, differences between KGHK‐immobilized and albumin‐immobilized disks were less significant (p = 0.120 and p = 0.289 for the vessel surface area and number of vessels, respectively). The developed methods have potential applications in biomaterial design applications for which selective neovascularization is desired. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 36–43, 2002
Differential sensitivities of plant and animal mitochondria to the herbicide paraquat
Authors: Vicente Joaquim A. F. , Peixoto Francisco , Lopes M. Ludovina , Madeira Vítor M. C.
Published: August 2002

Paraquat herbicide is toxic to animals, including humans, via putative toxicity mechanisms associated to microsomal and mitochondrial redox systems. It is also believed to act in plants by generating highly reactive oxygen free radicals from electrons of photosystem I on exposure to light. Paraquat also acts on non‐chlorophyllous plant tissues, where mitochondria are candidate targets, as in animal tissues. Therefore, we compared the interaction of paraquat with the mitochondrial bioenergetics of potato tuber, using rat liver mitochondria as a reference. Paraquat depressed succinate‐dependent mitochondrial Δψ, with simultaneous stimulation of state 4 O2 consumption. It also induced a slow time‐dependent effect for respiration of succinate, exogenous NADH, and N,N,N',N'‐tetramethyl‐p‐phenylenediamine (TMPD)/ascorbate, which was more pronounced in rat than in potato mitochondria. However, with potato tuber mitochondria, the Δψ promoted by complex‐I‐dependent respiration is insensitive to this effect, indicating a protection against paraquat radical afforded by complex I redox activity, which was just the reverse of to the findings for rat liver mitochondria. The experimental set up with the tetraphenyl phosphonium (TPP+)‐electrode also indivated production of the paraquat radical in mitochondria, also suggesting its accessibility to the outside space. The different activities of protective antioxidant agents can contribute to explain the different sensitivities of both kinds of mitochondria. Values of SOD activity and α‐tocopherol detected in potato mitochondria were significantly higher than in rat mitochondria, which, in turn, revealed higher values of lipid peroxidation induced by paraquat. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:322–330, 2001
A Management Accounting Framework
Authors: Cokins Gary
Published: August 2002

As nonfinancial managers increasingly need to understand their costs, there is confusion about competing cost
measurement methodologies. Should they choose standard costing, actual costing, throughput costing, or project
costing? The author suggests an overarching framework that supports the three purposes of management:
controlling, directing, and planning. © 2001 John Wiley & Sons, Inc.
Interferon regulatory factor‐1 mediates interferon‐γ‐induced apoptosis in ovarian carcinoma cells
Authors: Kim Eun‐Joo , Lee Joon‐Mo , Namkoong Sung‐Eun , Um Soo‐Jong , Park Jong‐Sup
Published: August 2002

Interferon‐γ (IFN‐γ), as one of interferon family that regulates antiviral, antiproliferative, and immunomodulatory responses, has been implicated for the growth regulation of ovarian cancer cells. However, the molecular mechanisms are not yet fully defined. To analyze detailed mechanisms, the ovarian cancer cell lines (2774, PA‐1, OVCAR‐3, and SKOV‐3) were treated with IFN‐γ. The growth of 2774 was most effectively suppressed than that of other cells in both time‐course and dose‐dependent experiments. The order of sensitivity in other cells was PA‐1 ≫ OVCAR‐3 > SKOV‐3 (not responded at all). The DNA fragmentation and DAPI staining assays suggested that the IFN‐γ‐mediated cytotoxicity could be triggered by apoptosis. The treatment induced IFN regulatory factor‐1 (IRF‐1) in two IFN‐γ‐sensitive cells (2774, PA‐1), whereas IRF‐1 was not induced in two IFN‐γ‐resistant cells (OVCAR‐3, SKOV‐3). The levels of p53 and p21WAF1 were not strikingly changed in all four cells. Interestingly, the expression of interleukin‐converting enzyme (ICE, or caspase‐1) was increased by the treatment in a kinetically consistent manner to the induction of IRF‐1. However, CD95 (Fas/APO‐1) was not changed. Apoptosis was greatly induced, when IRF‐1 was transiently expressed in PA‐1 without the treatment of IFN‐γ. However, it was repressed when IRF‐1 together with IRF‐2, an antagonist of IRF‐1, were coexpressed. In addition, the effect of IFN‐γ was reduced in the 2774 and PA‐1 cells stably expressing either IRF‐1 antisense or IRF‐2 sense, as shown by the cytotoxicity and FACS analysis. Furthermore, the IFN‐γ‐induced apoptosis was greatly reduced, when inhibitors of ICE were treated into PA‐1 cells. Taken together, these results suggest that IRF‐1 directly mediates the IFN‐γ‐induced apoptosis via the activation of caspase‐1 gene expression in IFN‐γ‐sensitive ovarian cancer cells. J. Cell. Biochem. 85: 369–380, 2002. © 2002 Wiley‐Liss, Inc.