bluuebunny/crossref_metadata_2025 huggingface dataset:
How many food additives are rodent carcinogens?
Authors: Johnson F.M.
Published: August 2002

One generally assumes that chemical agents added to foods are reasonably free of risks to human health, and practically everyone consumes some additives in his or her food daily throughout life. In the United States, the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act of 1938 requires food manufacturers to demonstrate the safety of food additives to the Food and Drug Administration (FDA). The Amendment contains a provision that prohibits approval of an additive if it is found to cause cancer in humans or animals. In the present study, data from the National Toxicology Program rodent bioassay (NTPRB) were used to identify a sample of approximately 50 rodent‐tested additives and other chemicals added to food that had been evaluated independently of the FDA/food industry. Surprisingly, the sample shows more than 40% of these food chemicals to be carcinogenic in one or more rodent groups. If this percentage is extrapolated to all substances added to food in the United States, it would imply that more than 1000 of such substances are potential rodent carcinogens. The NTP and FDA test guidelines use similar, though not necessarily identical, rodent test procedures, including near lifetime exposures to the maximum tolerated dose. The FDA specifies that test chemicals should be administered by the oral route. However, the oral route includes three methods of delivering chemicals, that is, mixed in the food or water or delivered by stomach tube (gavage). The NTP data show only 1 of 18 food chemicals mixed in the food are rodent carcinogens, but 16 of 23 gavage‐administered food chemicals are carcinogenic to rodents. The distribution suggests that among orally delivered chemicals, those administered in the feed will more likely prove to be noncarcinogens than chemicals given by gavage. The rodent data also reveal that effects may vary according to dose and genotype, as well as by route of administration, to further complicate extrapolation to humans. Human experience with known carcinogens such as tobacco, asbestos, and benzidine convinces us that environmental carcinogens constitute a real threat to human health, although predicting human carcinogens from rodent tests involves a number of uncertainties. These uncertainties do not mean that we should simply ignore the presence of carcinogens. Rather, in the interests of public safety, a serious effort should be made to resolve the questions surrounding the presence of chemicals identified as rodent carcinogens in our food. Environ. Mol. Mutagen. 39:69–80, 2002 Published 2002 Wiley‐Liss, Inc.
Carcinogen–DNA adducts in human breast epithelial cells
Authors: Gorlewska‐Roberts K. , Green B. , Fares M. , Ambrosone C.B. , Kadlubar F.F.
Published: August 2002

Diet and environmental exposures are often regarded as significant etiologic factors in human breast cancer. Chemicals that may be involved in these exposures include heterocyclic amines, aromatic amines, and polycyclic aromatic hydrocarbons, which also serve as strong mammary carcinogens in different animal models. In this study, we chose to quantify the major DNA adducts derived from one member of each of these classes of carcinogens, that is, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), 4‐aminobiphenyl (ABP), and benzo[a]pyrene (B[a]P), respectively, in DNA isolated from exfoliated ductal epithelial cells in human breast milk. Milk was collected from healthy, nonsmoking mothers. The isolated DNA was digested to 3′ nucleotides and subjected to 32P‐postlabeling. Adduct enrichment was achieved using Oasis Sep‐Paks and the analyses were conducted by HPLC using radiometric detection. Critical to the analyses were the syntheses of bis(phosphate) standards for the C8‐dG adducts of PhIP and ABP, and the N2‐dG adduct of B[a]P, which were added to each reaction as UV markers. Of the 64 samples analyzed, adducts were found in 31 samples. Thirty samples contained detectable levels of PhIP adducts, with a mean value of 4.7 adducts/107 nucleotides; 18 were positive for ABP adducts with a mean value of 4.7 adducts/107 nucleotides; and 13 were found to contain B[a]P adducts with a mean level of 1.9 adducts/107 nucleotides. These data indicate that women are exposed to several classes of dietary and environmental carcinogens and that these carcinogens react with DNA in breast ductal epithelial cells, the cells from which most breast cancers arise. Environ. Mol. Mutagen. 39:184–192, 2002. Published 2002 Wiley‐Liss, Inc.
From bacteria to humans: Lessons learned from a reductionist's view of ultraviolet light‐induced DNA lesions
Authors: Trosko James E.
Published: August 2002

What follows is a personal remembrance of how Dr. Richard Setlow influenced me as a young postdoctoral fellow at Oak Ridge National laboratory between 1963 and 1966. The narrative tries to place my “maturation” as a young, inexperienced scientist in the context of the cultural upheaval caused by the Vietnam war, of a Northerner facing a “culture‐shock” living in the South and in a revolution in molecular and radiation biology taking place at Oak Ridge National Laboratory at that time. The unique historic juxtaposition of Dr. Setlow's contribution of the discovery of UV‐induced pyrimidine dimers in bacterial DNA, being potentially the molecular lesion responsible for cell killing and mutagenesis, occurring as I was at Oak Ridge, and the wonderful working relationship I had with William Carrier, his technician, led to our discovery with James Regan that normal human cells repaired these lesion from their DNA. Amazingly, because of Dr. Setlow's challenge to me about my thoughts of the implications of his findings in bacteria, the chance visit to Oak Ridge National Laboratory by Dr. James Cleaver and my background as a human geneticist provided me the extraordinary opportunity to carry out a collaboration to test if human cancer prone syndromes might be deficient in the repair of these UV‐induced DNA lesions. With our finding that the direct demonstration of a lack of repair of UV‐induced pyrimidine dimers in cells from the skin cancer prone syndrome, xeroderma pigmentosum, opened up a new paradigm for the understanding of the molecular mechanism of carcinogenesis of both radiation and chemical carcinogenesis. From this investigator's vantage point in the history of the understanding of carcinogenesis, which has led us to the present point of “oncogenes” and “tumor suppressor genes”, the old adage by Newton, “I only saw further because I stood on the shoulder of giants”, is so applicable here. Dr. Setlow's shoulders were indeed among those of all of us that have made some small contribution in trying to understand this extremely complex process of human carcinogenesis. Environ. Mol. Mutagen. 38:118–121, 2001. © 2001 Wiley‐Liss, Inc.
Large scale wildlife monitoring studies: statistical methods for design and analysis
Authors: Pollock Kenneth H. , Nichols James D. , Simons Theodore R. , Farnsworth George L. , Bailey Larissa L. , Sauer John R.
Published: August 2002

Techniques for estimation of absolute abundance of wildlife populations have received a lot of attention in recent years. The statistical research has been focused on intensive small‐scale studies. Recently, however, wildlife biologists have desired to study populations of animals at very large scales for monitoring purposes. Population indices are widely used in these extensive monitoring programs because they are inexpensive compared to estimates of absolute abundance. A crucial underlying assumption is that the population index (C) is directly proportional to the population density (D). The proportionality constant, β, is simply the probability of ‘detection’ for animals in the survey. As spatial and temporal comparisons of indices are crucial, it is necessary to also assume that the probability of detection is constant over space and time. Biologists intuitively recognize this when they design rigid protocols for the studies where the indices are collected. Unfortunately, however, in many field studies the assumption is clearly invalid. We believe that the estimation of detection probability should be built into the monitoring design through a double sampling approach. A large sample of points provides an abundance index, and a smaller sub‐sample of the same points is used to estimate detection probability. There is an important need for statistical research on the design and analysis of these complex studies. Some basic concepts based on actual avian, amphibian, and fish monitoring studies are presented in this article. Copyright © 2002 John Wiley & Sons, Ltd.
Seismic response of self‐centring hysteretic SDOF systems
Authors: Christopoulos Constantin , Filiatrault André , Folz Bryan
Published: August 2002

The seismic response of single‐degree‐of‐freedom (SDOF) systems incorporating flag‐shaped hysteretic structural behaviour, with self‐centring capability, is investigated numerically. For a SDOF system with a given initial period and strength level, the flag‐shaped hysteretic behaviour is fully defined by a post‐yielding stiffness parameter and an energy‐dissipation parameter. A comprehensive parametric study was conducted to determine the influence of these parameters on SDOF structural response, in terms of displacement ductility, absolute acceleration and absorbed energy. This parametric study was conducted using an ensemble of 20 historical earthquake records corresponding to ordinary ground motions having a probability of exceedence of 10% in 50 years, in California. The responses of the flag‐shaped hysteretic SDOF systems are compared against the responses of similar bilinear elasto‐plastic hysteretic SDOF systems. In this study the elasto‐plastic hysteretic SDOF systems are assigned parameters representative of steel moment resisting frames (MRFs) with post‐Northridge welded beam‐to‐column connections. In turn, the flag‐shaped hysteretic SDOF systems are representative of steel MRFs with newly proposed post‐tensioned energy‐dissipating connections. Building structures with initial periods ranging from 0.1 to 2.0s and having various strength levels are considered. It is shown that a flag‐shaped hysteretic SDOF system of equal or lesser strength can always be found to match or better the response of an elasto‐plastic hysteretic SDOF system in terms of displacement ductility and without incurring any residual drift from the seismic event. Copyright © 2002 John Wiley & Sons, Ltd.
Seismic response of multi‐span simply supported bridges to a spatially varying earthquake ground motion
Authors: Zanardo Giovanna , Hao Hong , Modena Claudio
Published: August 2002

This paper carries out a parametrical study of the pounding phenomenon associated with the seismic response of multi‐span simply supported bridges with base isolation devices. In particular, the analyses focus on the causal relationship between pounding and the properties of a spatially varying earthquake ground motion. In order to include the effect of the torsional component of pounding forces on the seismic response of the whole structure, a three‐dimensional (3D) finite element model has been defined and 3D non‐linear time‐history analyses have been performed. A parametrical study on the size of the gaps between adjacent bridge decks has highlighted that the pounding effects are amplified when the spatially varying ground motion time histories at each support are considered. Because of a spatially varying input, the pounding forces can assume values 3–4 times larger than those derived by a conventional seismic analysis with uniform input or with spatial input but considering ground motion wave passage effect only. The numerical results show that in order to achieve an acceptably safe structural performance during seismic events, a correct design of the isolation devices should take into account the relative displacements calculated by means of a non‐linear time‐history analysis with multi‐support excitation. Copyright © 2002 John Wiley & Sons, Ltd.
Substructuring of dynamical systems via the adaptive minimal control synthesis algorithm
Authors: Wagg D. J. , Stoten D. P.
Published: August 2002

In this paper we consider the concept of modelling dynamical systems using numerical–experimental substructuring. This type of modelling is applicable to large or complex systems, where some part of the system is difficult to model numerically. The substructured model is formed via the adaptive minimal control synthesis (MCS) algorithm. The aim of this paper is to demonstrate that substructuring can be carried out in real time, using the MCS algorithm. Thus, we reformulate the MCS algorithm into a substructuring form. We introduce the concepts of a transfer system, and carry out numerical simulations of the substructuring process using a coupled three mass example. These simulations are compared with direct simulations of a three mass system. In addition we consider the stability of the substructuring algorithm, which we discuss in detail for a class of second‐order transfer systems. A numerical–experimental system is considered, using a small‐scale experimental system, for which the substructuring algorithm is implemented in real time. Finally we discuss these results, with particular reference to the future application of this method to modelling large‐scale structures subject to earthquake excitation. Copyright © 2001 John Wiley & Sons, Ltd.
Silencing the self and suppressed anger: relationship to eating disorder symptoms in adolescent females
Authors: Zaitsoff Shannon L. , Geller Josie , Srikameswaran Suja
Published: August 2002

Objective:

This study examined the extent to which inhibited expression of negative feelings and an interpersonal style that focuses on others' needs and expectations are related to eating disorder symptoms in adolescent females.

Method:

Female high school adolescents (N = 235) completed the Anger Expression Scale, the Silencing the Self Scale, and measures of eating disorder symptoms, self‐esteem, and psychological adjustment.

Results:

Adolescents with higher eating disorder symptom scores had significantly higher levels of anger inhibition and silencing the self scores. In regression analyses, the Silencing the Self and Anger Expression Scales contributed statistically significant unique variance to cognitive and behavioural eating disorder symptoms scores after controlling for shape‐ and weight‐based self‐esteem. A similar, though weaker, pattern of results was found after controlling for global self‐esteem.

Discussion:

These results partially replicate relationships found between inhibited self‐expression and eating disorder symptoms in adult clinical samples. Implications for the development of eating disorder symptoms are addressed. Copyright © 2002 John Wiley & Sons, Ltd and Eating Disorders Association.
History and current state of treatment for eating disorders in Romania
Authors: Joja Oltea
Published: August 2002

Romania has a population of around 22.5 million of which 51 per cent are female and around 36 per cent are girls and women between 10 and 45 years of age. Just over half of the total population live in cities. There have been major changes in Romania since 1989 and these have had important effects upon the lives of women. Women have come to be more preoccupied with issues of individuality and now show interest in new cultural models. Slimness has come to be highly valued. There has been a growing interest both in women's magazines offering dieting schedules and in western movies showing eating attitudes and behaviours as symptoms of disorder. None of this sort of information was public in Romania before 1989. Copyright © 2001 John Wiley & Sons, Ltd and Eating Disorders Association.
Variability of dry sediment bulk density between and within retention ponds and its impact on the calculation of sediment yields
Authors: Verstraeten Gert , Poesen Jean
Published: August 2002

Monitoring sediment yields from catchments is important for assessing overall denudation rates and the impact of environmental change. One of the methods used to assess sediment yield is by quantifying sedimentation rates in reservoirs, lakes or small ponds. Before reliable sediment yield values (t ha−1 a−1) can be computed from such sedimentation records, the measured sediment volumes need to be converted to sediment masses using representative values of the dry sediment bulk density. In textbooks, simple relations predicting dry sediment bulk density from sediment texture, time since deposition and hydrologic condition are presented. In this study, 13 small flood retention ponds in central Belgium were sampled to reveal the variability in dry sediment bulk density and to test the commonly used relations to predict dry sediment bulk density. Dry sediment bulk density varies not only between the selected ponds (0·78–1·35 t m−3) but also within individual ponds (coefficient of variation at 95 per cent ranges from 7 to 80 per cent). The observed variability can be attributed primarily to the hydrologic condition of the retention pond and, also, to sediment texture. The existing relations are not a reliable predictor for the observed dry bulk densities, because they are primarily based on sediment texture. Thus, when using volumetric sedimentation data from small ponds with varying hydrologic condition to predict sediment yield, existing relations predicting dry sediment bulk density cannot be applied. Instead, frequent and dense sampling of sediments is necessary to calculate a representative value of the dry sediment bulk density. Copyright © 2001 John Wiley & Sons, Ltd.
Three‐dimensional flow structure around small‐scale bedforms in a simulated gravel‐bed environment
Authors: Lawless Mark , Robert André
Published: August 2002

Pebble clusters are common small‐scale morphological features in gravel‐bed rivers, occupying as much as 10 per cent of the bed surface. Important links exist between the presence of pebble clusters and the development of flow structures. These links are poorly understood at the three‐dimensional level. Particularly neglected has been the effect of clusters on the lateral flow characteristics. A laboratory study was conducted using a hydraulic flume, within which simulated pebble clusters were superimposed onto a plane bed of gravel material. High‐resolution three‐dimensional flow data were collected above the bed at two different flow depths using an acoustic Doppler velocimeter. The results present evidence of the importance of lateral flow in the development of turbulent flow structure. Narrow regions of high lateral and downstream turbulence intensity exist to both sides of clusters and in a three‐dimensional separation zone in their lee. This may indicate the presence of horseshoe‐type vortical structures analogous to those identified in less hydraulically rough environments. However, it is likely that these structures are more complicated given the mutual interference of the surrounding medium. The lateral flow was also identified as a key component in the upwelling identified by other authors in the lee of pebble clusters. The results of the vertical flow analysis confirm the hypothesis that six regions with distinct vertical flow characteristics exist above clusters: flow acceleration up the stoss‐side of the cluster; recirculation behind the cluster in the wake region; vortex shedding from the pebble crest and shear layer; flow reattachment downstream of the cluster; upwelling of flow downstream of the point of reattachment; and recovery of flow. Copyright © 2001 John Wiley & Sons, Ltd.
An experimental study on the ripple–dune transition
Authors: Robert André , Uhlman William
Published: August 2002

Flume experiments were conducted on different bed stages across the ripple–dune transition. As flow velocity increases, an initially flat bed surface (made of fairly uniform sandy material) is gradually transformed into a two‐dimensional rippled bed. With further increase in velocity, two‐dimensional ripples are replaced by irregular, linguoid ripples. As the average velocity necessary for the ripple–dune transition to occur is imposed on the bed surface, these non‐equilibrium linguoid ripples are further transformed into larger, two‐dimensional dunes. For each of these stages across the transition, a concrete mould of the bed was created and the flow structure above each fixed bed surface investigated. An acoustic Doppler velocimeter was used to study the flow characteristics above each bed surface. Detailed profiles were used along a transect located in the middle of the channel. Results are presented in the form of spatially averaged profiles of various flow characteristics and of contour maps of flow fields (section view). They clearly illustrate some important distinctions in the flow structure above the different bedform types associated with different stages during the transition. Turbulence intensity and Reynolds stresses gradually increase throughout the transition. Two‐dimensional ripples present a fairly uniform spatial distribution of turbulent flow characteristics above the bed. Linguoid ripples induce three‐dimensional turbulence structure at greater heights above the bed surface and turbulence intensity tends to increase steadily with height above bed surface in the wake region. A very significant increase in turbulence intensity and momentum exchange occurs during the transition from linguoid ripples to dunes. The turbulent flow field properties above dunes are highly dependent on the position along and above the bed surface and these fields present a very high degree of spatial variability (when compared with the rippled beds). Further investigations under natural conditions emphasizing sediment transport mechanisms and rates during the transition should represent the next step of analysis, together with an emphasis on quadrant analysis. Copyright © 2001 John Wiley & Sons, Ltd.
Nobody knows my name: In praise of african american evaluators who were responsive
Authors: Hood Stafford
Published: August 2002

The essential place of race and culture in the meanings of responsive evaluation are argued through (1) a historical accounting of the significant but inexplicably unknown contributions of early African American evaluators and (2) the unassailable warrant for contemporary responsiveness to our “long silenced cultures of color.”
New directions for ECB
Authors: Baizerman Michael , Compton Donald W. , Hueftle Stockdill Stacey
Published: August 2002

The authors bring together the literature and the case studies in a framework for practicing and studying ECB as art, craft, and science.
Embryonic expression and regulation of the large zinc finger protein KRC
Authors: Hicar Mark D. , Robinson Michael L. , Wu Lai‐Chu
Published: August 2002

Summary: KRC fusion proteins bind to the κB enhancer motif and to the signal sequences of V(D)J recombination. Here we have characterized endogenous KRC in mouse embryos and lymphoma cell lines. Starting from midgestation, neuronal‐ and lymphoid‐restricted expression of KRC was observed from the dorsal root ganglia, trigeminal ganglion, thymus, and cerebral cortex. Several B‐cell lines produced an alternatively spliced KRC transcript of 4.5 kb and a 115‐kDa DNA‐binding protein isoform. Additionally, that KRC transcript was induced by lipopolysaccharide, a potent activator of cells in immunity and inflammation. In genetic‐engineered B cells stably transfected with inducible expression vectors for the recombination activating genes RAG1, RAG2, or both, the avidity of KRC to DNA was markedly decreased when RAG1 and RAG2 were overexpressed. We hypothesize that KRC may function in developing thymocytes and neurons, where its role might be transcription regulation or DNA recombination. genesis 33:8–20, 2002. © 2002 Wiley‐Liss, Inc.
Hypomorphic phenotype in mice with pituitary‐specific knockout of steroidogenic factor 1
Authors: Zhao Liping , Bakke Marit , Krimkevich Yelena , Cushman Lisa J. , Parlow A. F. , Camper Sally A. , Parker Keith L.
Published: August 2002

Summary: The bacteriophage Cre recombinase provides a powerful approach for tissue‐specific gene inactivation. Using a Cre transgene driven by the common alpha subunit of glycoprotein hormones (αGSU‐Cre), we have previously inactivated steroidogenic factor 1 (SF‐1) in the anterior pituitary, causing hypogonadotropic hypogonadism with sexual infantilism, sterility, and severe gonadal hypoplasia. We now explore the molecular mechanisms underlying a hypomorphic gonadal phenotype in mice carrying two floxed SF‐1 alleles (F/F) relative to mice carrying one recombined and one floxed allele (F/R). Because their Cre‐mediated disruption of the locus encoding SF‐1 was less efficient, αGSU‐Cre, F/F mice retained some gonadotropin‐expressing cells in the anterior pituitary, thereby stimulating some gonadal function. This novel in vivo model for exploring the effects of differing levels of gonadotropins on gonadal development highlights the need for careful genotype‐phenotype comparisons in studies using Cre recombinase to produce tissue‐specific knockouts. genesis 30:65–69, 2001. © 2001 Wiley‐Liss, Inc.
Similar myogenic functions for myogenin and MRF4 but not MyoD in differentiated murine embryonic stem cells
Authors: Sumariwalla Veera M. , Klein William H.
Published: August 2002

Summary: The emergence of four genes encoding myogenic bHLH transcription factors in the stem vertebrate is a unique feature of vertebrate evolution that led to the acquisition of new target genes and novel regulatory circuits for skeletal muscle formation. One unresolved question is the extent to which each factor has evolved specialized functions for regulating muscle gene transcription. We have developed a system using differentiated myogenin (‐/‐) embryonic stem (ES) cells to determine whether other myogenic factors can replace myogenin's function in muscle differentiation. Previously, we showed that constitutively expressed myogenin restores myofiber formation in differentiated myogenin (‐/‐) ES cells, but constitutively expressed MyoD does not. Here, we confirm the distinction between myogenin and MyoD using another expression vector and show that constitutively expressed MRF4 leads to myofiber formation in myogenin's absence. Our analysis reveals a correlation between the levels of myogenin plus MRF4 and the extent of myofiber formation, suggesting a synergy between these factors. The results indicate that unlike MyoD, MRF4 plays a role similar to myogenin in skeletal muscle differentiation. genesis 30:239–249, 2001. © 2001 Wiley‐Liss, Inc.
Genome‐wide linkage analysis of blood pressure in Mexican Americans
Authors: Atwood Larry D. , Samollow Paul B. , Hixson James E. , Stern Michael P. , MacCluer Jean W.
Published: August 2002

The genetic mechanisms that control variation in blood pressure level are largely unknown. One of the first steps in understanding those mechanisms is the localization of the genes that have a significant effect on blood pressure. We performed genome scans of systolic (SBP) and diastolic blood pressure (DBP) on a population‐based sample of families in the San Antonio Family Heart Study. A likelihood‐based Mendelian model incorporating genotype‐specific effects of sex, age, age2, BMI, and blood pressure (SBP or DBP, as appropriate) as covariates was used to perform two‐point lodscore (Z) linkage on 399 polymorphic markers. Results showed that the genotype‐specific covariate effects were highly significant for both SBP and DBP. Linkage results showed that a quantitative trait locus (QTL) influencing DBP was significantly linked to D2S1790 (Z = 3.92, θ = 0.00) and showed suggestive linkage to D8S373 (Z = 1.92, θ = 0.00). A QTL influencing SBP showed suggestive linkage to D21S1440 (Z = 2.82, θ = 0.00) and D18S844 (Z = 2.09, θ = 0.11). Without the genotype‐specific effects in the model, the linkage to D2S1790 was not even suggestive (Z = 1.33, θ = 0.09); thus genotype‐specific modeling was crucial in detecting this linkage. A comparison with linkage studies based in other populations showed that the significant linkage to D2S1790 has been replicated at the same marker in the Quebec Family Study. The replicated significant linkage at D2S1790 may begin to establish the locations of the genes that significantly affect blood pressure across several human ethnic groups. Genet. Epidemiol. 20:373–382, 2001. © 2001 Wiley‐Liss, Inc.
Stratigraphy and palaeoenvironmental development of Quaternary coarse clastic beach deposits at Plage de Mezpeurleuch, Brittany (France)
Authors: Haslett Simon K. , Curr Richard H. F.
Published: August 2002

Quaternary deposits are described from well‐exposed sections in cliffs at Plage de Mezpeurleuch, Finistère, Brittany (France). The general lithostratigraphic sequence comprises Holocene perched dune sand, calcrete and palaeosol overlying Weichselian head and coarse clastic palaeobeach units attributed to the last interglacial (Eemian–isotope substage 5e). A lower and an upper palaeobeach, separated by a thin head deposit, are reported resting on an irregular palaeorock platform eroded in Hercynian granite. From a comparison with modern coastal environments a palaeoenvironmental interpretation of the palaeobeach deposits is made. Erosionally bounded facies of the lower palaeobeach, are considered to be a transgressive sequence preserved by drowning associated with a rapid rise in relative sea‐level. Its subsequent abandonment is attributed to a relative sea‐level fall, which allowed a terrestrial environment to develop briefly. Facies of the upper palaeobeach however indicate a prograding shoreline developed during a prolonged period of relatively stable sea‐level. These sea‐level observations are in good agreement with other evidence for a brief widespread intra‐Eemian cold event. Copyright © 2001 John Wiley & Sons, Ltd.
Mechanisms of apoptosis induced by purine nucleosides in astrocytes
Authors: Di Iorio Patrizia , Kleywegt Sonya , Ciccarelli Renata , Traversa Ugo , Andrew Craig M. , Crocker Candice E. , Werstiuk Eva S. , Rathbone Michel P.
Published: August 2002

Astrocytes release adenine‐based and guanine‐based purines under physiological and, particularly, pathological conditions. Thus, the aim of this study was to determine if adenosine induced apoptosis in cultured rat astrocytes. Further, if guanosine, which increases the extracellular concentration of adenosine, also induced apoptosis determined using the TUNEL and Annexin V assays. Adenosine induced apoptosis in a concentration‐dependent manner up to 100 μM. Inosine, hypoxanthine, guanine, and guanosine did not. Guanosine or adenosine (100 μM) added to the culture medium was metabolized, with 35% or 15%, respectively, remaining after 2–3 h. Guanosine evoked the extracellular accumulation of adenosine, and particularly of adenine‐based nucleotides. Cotreatment with EHNA and guanosine increased the extracellular accumulation of adenosine and induced apoptosis. Inhibition of the nucleoside transporters using NBTI (100 μM) or propentophylline (100 μM) significantly decreased but did not abolish the apoptosis induced by guanosine + EHNA or adenosine + EHNA, respectively. Apoptosis produced by either guanosine + EHNA or adenosine + EHNA was unaffected by A1 or A2 adenosine receptor antagonists, but was significantly reduced by MRS 1523, a selective A3 adenosine receptor antagonist. Adenosine + EHNA, not guanosine + EHNA, significantly increased the intracellular concentration of S‐adenosyl‐L‐homocysteine (SAH) and greatly reduced the ratio of S‐adenosyl‐L‐methioine to SAH, which is associated with apoptosis. These data demonstrate that adenosine mediates apoptosis of astrocytes both, via activation of A3 adenosine receptors and by modulating SAH hydrolase activity. Guanosine induces apoptosis by accumulating extracellular adenosine, which then acts solely via A3 adenosine receptors. GLIA 38:179–190, 2002. © 2002 Wiley‐Liss, Inc.
Increased syndecan expression by pleiotrophin and FGF receptor‐expressing astrocytes in injured brain tissue
Authors: Iseki Ken , Hagino Seita , Mori Tetsuji , Zhang Yuxiang , Yokoya Sachihiko , Takaki Hiromi , Tase Choichiro , Murakawa Masahiro , Wanaka Akio
Published: August 2002

Syndecan‐1, ‐2, ‐3, and ‐4 are heparan sulfate proteoglycans that are differentially expressed during development and wound repair. To determine whether syndecans are also involved in brain injury, we examined the expression of syndecan core proteins genes in cryo‐injured mouse brain, using in situ hybridization. All syndecan mRNA transcripts were similarly expressed in the region surrounding the necrotic tissue, exhibiting peak levels at day 7 after injury. Comparison with cellular markers showed that reactive astrocytes were the primary source of syndecans. Syndecans serve as co‐receptors for fibroblast growth factor (FGF) and as a reservoir for another heparin‐binding growth factor, pleiotrophin (PTN, or heparin‐binding growth‐associated molecule. In our model, FGF receptor1 (FGFR1) and PTN mRNA levels were upregulated in reactive astrocytes. The distribution patterns of FGFR1 and PTN overlapped considerably with those of syndecan‐1 and ‐3 mRNAs, respectively. These results suggest that syndecans are expressed primarily in reactive astrocytes, and may provide a supportive environment for regenerating axons in concert with heparin‐binding growth factors (e.g., FGF and PTN) in the injured brain. GLIA 39:1–9, 2002. © 2002 Wiley‐Liss, Inc.
Basic principles of immunological surveillance of the normal central nervous system
Authors: Hickey William F.
Published: August 2002

Unlike most bodily organs, the central nervous system (CNS) exists behind a blood–tissue barrier designed to minimize the passage of cells and macromolecules into the neural parenchyma. Yet, the CNS is routinely and effectively surveyed by the immune system. This review examines the mechanisms and participants in this immunological surveillance mechanism. The nature of the healthy blood–brain barrier, factors modifying it, and its central position in determining the number and nature of leukocytes permitted to enter, are considered. In addition the role in surveillance played by lymphatic drainage, migrating T and B lymphocytes, and elements of the monocyte/macrophage/microglia family are considered. While all these participants are known to be important in responding to a CNS antigen and/or establishing a site of inflammation in the nervous system, they also are major elements in maintaining the homeostasis of the CNS and permitting the necessary immunological surveillance of that organ. GLIA 36:118–124, 2001. © 2001 Wiley‐Liss, Inc.
Depressive symptoms among poststroke patients in Japan: frequency distribution and factor structure of the GDS
Authors: Schreiner Andrea S. , Morimoto Tomoko , Asano Hitoshi
Published: August 2002

Objective

The present study examined the nature, prevalence, and covariates of depressive symptoms among home‐dwelling poststroke patients in Japan using the Geriatric Depression Scale Short Form (GDS‐1). Poststroke results were compared with those of elderly with affective disorders and with those of healthy nonstroke elderly.

Methods

Poststroke patients (n = 101) who did not also have a diagnosis of Alzheimer's dementia, were identified from patient records at seven randomly selected hospitals with outpatient rehabilitation clinics in a metropolitan area in western Japan and invited to participate in the study. All instruments were interview‐administered.

Results

GDS scores did not correlate with age, sex, education, functional dependence, aphasia, paralysis or presence of other chronic illnesses. However, GDS scores did correlate significantly with self‐rated general health and poststroke duration. Compared with the frequency distribution in a psychiatric sample, poststroke patients had higher positive affect and lower depressed mood but similar social withdrawal scores. The factor structure of the poststroke sample differed from that of nonstroke elderly in that depressed mood items loaded with items for energy loss and memory problems.

Conclusion

Despite the fact that 62% of subjects scored ≥ 6 on the GDS, none were currently receiving assessment and/or treatment for their depressive symptoms. The frequency distribution and factor structure suggest that poststroke GDS scores reflect endorsement of functional losses such as decreased energy and impaired memory and subsequent feelings of helplessness, boredom and social withdrawal rather than decreased positive affect. Treatment should focus on dealing with these issues. Copyright © 2001 John Wiley & Sons, Ltd.
Neural representation of verb meaning: An fMRI study
Authors: Grossman Murray , Koenig Phyllis , DeVita Chris , Glosser Guila , Alsop David , Detre John , Gee James
Published: August 2002

The neural basis for verb comprehension has proven elusive, in part because of the limited range of verb categories that have been assessed. In the present study, 16 healthy young adults were probed for the meaning associated with verbs of MOTION and verbs of COGNITION. We observed distinct patterns of activation for each verb subcategory: MOTION verbs are associated with recruitment of left ventral temporal‐occipital cortex, bilateral prefrontal cortex and caudate, whereas COGNITION verbs are associated with left posterolateral temporal activation. These findings are consistent with the claim that the neural representations of verb subcategories are distinct. Although the “sensory‐motor” hypothesis may play a role in explaining activation associated with MOTION verbs, the left posterolateral temporal distribution of cortical activation associated with COGNITION verbs cannot be easily explained by the “sensory‐motor” hypothesis. We suggest that left posterolateral temporal activation supports aspects of lexical semantic processing concerned with the neural representation of propositional knowledge contributing to COGNITION verbs. Hum. Brain Mapping 15:124–134, 2002. © 2002 Wiley‐Liss, Inc.
Brief visual stimulation allows mapping of ocular dominance in visual cortex using fMRI
Authors: Goodyear Bradley G. , Menon Ravi S.
Published: August 2002

We have used high spatial resolution (0.55 mm × 0.55 mm) functional magnetic resonance imaging (fMRI) to show that when stimulus duration is brief (<6 sec), the hyperoxic hemodynamic response to neural activity can resolve the columnar architecture of ocular dominance within the primary visual cortex of humans. Our fMRI maps of ocular dominance columns are strikingly similar in appearance, size, and orientation to those reported in the literature using optical imaging of intrinsic signals (OIS) in animal cortex and histology of post‐mortem human specimens. We also demonstrate that under brief visual stimulation conditions, our results are consistent over repeated experiments. This is not the case for long duration stimuli (≥10 sec). A simulated random data set exhibited the same response properties as maps obtained when using these prolonged visual stimuli. Our results suggest that brief visual stimulation is essential for fMRI to successfully resolve ocular dominance columns using the hyperoxic phase of the hemodynamic response to neural activity at our prescribed spatial resolution. Hum. Brain Mapping 14:210–217, 2001. © 2001 Wiley‐Liss, Inc.
What kinds of professional international opportunities may be secured for faculty?
Authors: Fung Samuel , Filippo Joe
Published: August 2002

U.S. professors have a variety of opportunities, including study abroad and faculty exchange programs, to work in another country, which can enrich a professor's cross‐cultural perspectives.
Benchmarking in student affairs
Authors: Mosier Robert E. , Schwarzmueller Gary J.
Published: August 2002

This chapter provides an overview of benchmarking in student affairs and provides several case studies that demonstrate how benchmarking has been used in student housing.
Changing the first line drug for malaria treatment—cost‐effectiveness analysis with highly uncertain inter‐temporal trade‐offs
Authors: Goodman Catherine A. , Coleman Paul G. , Mills Anne J.
Published: August 2002

Access to effective treatment would substantially reduce the burden of malaria in sub‐Saharan Africa, but resistance to chloroquine, the most commonly used first line drug, is now widespread. There has been considerable debate over the level of chloroquine resistance at which a new first line drug should be adopted. Two issues make this an extremely complex decision: it involves trade‐offs in costs and health outcomes over time; and many of the parameters are uncertain. A modelling approach was identified as appropriate for addressing these issues. The costs and effects of changing from chloroquine to sulphadoxine‐pyrimethamine (SP) as the first line drug were modelled over 10 years, allowing for growth in drug resistance. Probabilistic sensitivity analysis was used to allow for the high levels of parameter uncertainty. The optimal year of switch was highly dependent on both empirical values, such as initial resistance and resistance growth rates, and on subjective values, such as the time preferences of policy‐makers. It was not possible to provide policy‐makers with a definitive threshold resistance level at which to switch, but the model can be used as an analytical tool to structure the problem, explore trade‐offs, and identify areas for which data are lacking. Copyright © 2001 John Wiley & Sons, Ltd.
Vascularization in the transition area between free grafted soft tissues and pre‐irradiated graft bed tissues following preoperative radiotherapy in the head and neck region
Authors: Schultze‐Mosgau Stefan , Grabenbauer Gerhard G. , Radespiel‐Troöger Martin , Wiltfang Joörg , Ries Jutta , Neukam Friedrich Wilhelm , Roödel Franz
Published: August 2002

Background

The healing of free vascular grafts in a pre‐irradiated graft bed is characterized by an increased risk of wound healing disorders. For that reason, the aim of this study was to examine quantitative vascularization pattern between free vascular grafts and the pre‐irradiated graft bed as a function of the preoperative irradiation dose.

Methods

A total of 217 free microvascular hard and soft tissue grafts were used within 199 patients in the head and neck region to cover defects after ablative tumor surgery. Seventy‐six patients (group 1) had no prior radiation (RT), 50 patients (group 2) were treated with preoperative radiochemotherapy using 40 to 50 Gy and 5‐FU/cisplatin, and 73 patients (group 3) had prior RT (60–70 Gy) between 1 and 7 years before surgery. After healing of the grafts, samples were taken from 42 patients from the graft, the irradiated graft bed, and the transition area between graft and irradiated graft bed. Samples were analyzed as follows: capillary sprouting, structural changes, and distribution patterns were analyzed by immunohistochemical staining (CD34 labeling of capillary endothelium). Three histological sections (2–4 μm) per sample were examined histomorphometrically (ratio capillary area/total area, capillary lumen, and the number of capillaries) by (National Institute of Health) NIH‐image‐digitized measurements. A statistical analysis was performed using the Kruskal‐Wallis and Mann‐Whitney test (two‐tailed p < .05).

Results

The success rate of vascular grafts in group 1 (0 Gy) was 94%, in group 2 (40–50 Gy/5‐FU/cisplatin) 90%, in group 3 (60–70 Gy) 84%. In contrast to groups 1 and 2, group 3 showed qualitatively reduced and more irregular capillary distribution with more marked pericapillary fibrosis in the irradiated tissue. Quantitatively, the ratio capillary area/total area, as a marker of improved capillarization, was significantly reduced in group 3 (median 0.01; IQR 0.02) compared with group 1 (median 0.53; IQR 0.32) and group 2 (median 0.44; IQR 1.40) (p < .001).

Conclusion

After preoperative RT, vascularization of the graft bed decreased continuously as a function of the total dose and time after RT. The results strongly advocate the use of a primary reconstruction after a time interval between 4 and 6 weeks following preoperative RT and suggest the use of a total radiation dose of 40 to 50 Gy. © 2002 John Wiley & Sons, Inc. Head Neck 24: 42–51, 2002.
T stage as prognostic factor in irradiated localized squamous cell carcinoma of the nasal vestibule
Authors: Kummer Eelco , Rasch Coen R. N. , Keus Ronald B. , Tan I. Bing , Balm Alfons J. M.
Published: August 2002

Background

To investigate the impact of T stage according to Wang on the prognosis of irradiated nasal vestibule carcinoma.

Patients and Methods

Treatment results of 47 patients were retrospectively analyzed. Treatment consisted of external beam radiotherapy (n = 26) or interstitial radiotherapy (n = 19) or a combination of both (n = 2) for a primary, localized, squamous cell carcinoma of the nasal vestibule. Mean follow‐up was 5 years and 7 months.

Results

T1/T2 tumors: Local control was achieved in 40 of 44 patients; surgical salvage was possible in 2 of 4 local failures. Five patients had recurrences in the neck, and four of them could be salvaged surgically. One patient had distant metastases develop. T3 tumors (n = 3): no T3 tumor could locally be cured by radiotherapy. One patient was salvaged surgically but died of regional and distant metastases. Disease‐specific survival is significantly correlated with T stage according to Wang (p = .0001). Most (85%) patients were smokers, and eight of them (20%) had a second primary tumor develop in the lungs.

Conclusions

The effect of radiotherapy is significantly correlated with T stage (p = .0001) and hence less successful in T3 lesions as primary treatment option. The high incidence of second primary tumors in the lung is indicative for a similar carcinogenic influence of smoking on the nasal vestibule. © 2002 Wiley Periodicals, Inc. Head Neck 24: 268–273, 2002; DOI 10.1002/hed.10023
Clinical relevance of Fas (APO‐1/CD95) expression in laryngeal squamous cell carcinoma
Authors: Jäckel Martin C. , Mitteldorf Christina , Schweyer Stefan , Füzesi Làszlò
Published: August 2002

Background

Expression of Fas receptors renders tumor cells potentially susceptible to the host immune system. In squamous cell carcinomas of the head and neck, Fas has recently been found to be down‐regulated in some cases; its prognostic value and correlation with clinicopathologic parameters, however, is yet to be delineated.

Methods

Paraffin‐embedded specimens of 88 primary laryngeal squamous cell carcinomas were investigated for Fas protein expression by immunohistochemistry. Apoptotic tumor cells were visualized using the nick end labeling method. To assess the immunologic reaction to the neoplasm, the intensity of lymphoplasmocytic stroma reaction was determined. The mean follow‐up time amounted to 45.9 months (range, 1–144 months).

Results

In tumor‐adjacent normal mucosa and in most well‐differentiated tumors, Fas expression was restricted to basal and parabasal cell layers. A diffuse pattern of staining reactions predominated in high‐grade lesions (p < .001). The degree of Fas expression revealed a positive relationship with the intensity of lymphoplasmocytic stroma reaction (p = .002) but was unrelated to clinicopathologic parameters and to apoptotic rates of tumors. Neither Fas nor the lymphoplasmocytic stroma reaction had any impact on patient survival.

Conclusions

Up‐regulation of cell surface Fas expression in laryngeal carcinoma seems to have a stimulatory effect on the immune cell infiltration of the stromal tissue. Its lack of clinical relevance might be due to an inhibition of intracellular Fas signal transduction, which represents a frequent strategy of tumor cells to escape Fas‐mediated apoptosis. © 2001 John Wiley & Sons, Inc. Head Neck 23: 646–652, 2001.