bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative Approaches to Market-area Structure in the Urban System
Authors: Parr John B.
Published: July 2002

It is argued that the market-area structure within the typical model of an urban system does not conform satisfactorily to the pattern customarily observed. The market-area structure of the standard model of a central place system is modified, by applying, in turn, two additional frameworks: the economic law of market areas and the law of retail gravitation. It is demonstrated that each application results in a more realistic pattern of market areas, while preserving the hierarchical structure of the central place system. The strengths and weaknesses of each approach are examined, and further aspects of both approaches are then considered.
Judging Development Control Decisions
Authors: Willis K.G.
Published: July 2002

Development control decisions seek to ensure that planning applications conform to development plans and that environmental externalities are minimised. The cognitive continuum and lens models provide frameworks for describing how people make these development control decisions in practice under the Town and Country Planning Acts in England. A discrete choice decision model is developed to analyse the recommendations of the planning officer and the decisions of the planning committee, using planning applications to develop mineral deposits as a case example. The problem of a 'gold standard' is discussed against which decisions can be judged. The discrete choice model of planning decisions has a high success rate in predicting development control judgements. The results demonstrate that cue utilisation by subjects using intuitive decision methods is poor. Planning officers and committee members engage in differential dimension focus: whilst they believe in complexity, in reality their judgements depend upon just a few major variables.
Planned Communities, Self-containment and Commuting: A Cross-national Perspective
Authors: Cervero Robert
Published: July 2002

Many new towns are planned as balanced, self-contained communities. This paper examines the association between how self-contained new towns are and how their residents and workers commute, drawing upon experiences in the US, the UK, metropolitan Paris and greater Stockholm. While American new towns are fairly self-contained, their commuting characteristics are largely indistinguishable from less-planned control communities. Britain's most recent new towns are highly balanced and self-contained, yet they are comparatively auto-dependent. By contrast, the rail-served new towns outside Paris and Stockholm are the least self-contained among the new towns studied; however, most external commutes are by rail transit or other non-auto modes. In general, there was an inverse relationship between self-containment and transit commuting in the European new towns studied. The paper concludes that other policies, like coordinated transit services, more strongly influence commuting choices among new town residents and workers than initiatives aimed at jobs-housing balance and self-sufficiency.
Sources of Difference in Information Used by Black and White Housing Seekers: An Exploratory Analysis
Authors: Newburger Harriet
Published: July 2002

Survey data are used to examine search characteristics of recent home-buyers in two Boston neighbourhoods and two suburban Boston towns. Significant differences are found for black and white buyers, with blacks tending to use fewer information sources and to inspect fewer houses before purchase. The marketing of 'for sale' properties in the two Boston neighbourhoods covered by the survey is also examined. It appears to be more difficult to collect information from newspapers and brokers in predominantly black parts of these neighbourhoods than in predominantly white parts. While other factors considered in the paper can also explain lower information use by black home-buyers, it seems plausible that greater difficulty in collecting information in the black areas is a contributing factor.
Rethinking the Economics of Location and Agglomeration
Authors: McCann Philip
Published: July 2002

Fundamental problems exist with the classical characterisation of agglomeration economies, since such definitions do not reflect the various cost issues on which firms may wish to economise. A lack of understanding of the relationship between the notions of market hierarchies and locational behaviour leads to confusion not only in applied economic interpretation, but more fundamentally in the construction of theoretical location models. In particular, neo-classical location theory can be shown to be crucially flawed as a basis for spatial analysis. This paper therefore attempts to provide an alternative definition of the various types of agglomeration economies such that the various strands of economic theory might be used in a more rigorous manner in the discussion of spatial increasing returns.
New Process Technology and the Regeneration of the Manufacturing Sector of an Urban Economy
Authors: Foley P.D. , Watts H.D.
Published: July 2002

Local economic development strategies for the manufacturing sectors of urban areas have tended to focus on either inward investment or the stimulation of new firms. This paper argues more attention should be focused upon existing large manufacturing operations. The introduction of new process technologies into existing establishments may enhance the competitiveness of an urban economy. Using data from a new survey of the larger metal-using establishments in the Sheffield economy the empirical work highlights the difficulties that can be encountered in the introduction of new process technology. The concluding section outlines a number of policy considerations which may indicate a way forward for local administrations seeking to encourage the introduction of new process technology into large plants in traditional manufacturing sectors.
Market-type Mechanisms, Market Testing and Market Making: A Longitudinal Study of Contractor Interest in Tendering
Authors: Milne Robin G.
Published: July 2002

Market testing is evaluated in the context of market-type mechanisms, for the efficiency gains it achieves. It has been part of public policy in the UK since 1979, and mandatory for defined support services, first in central government departments, then in the National Health Service and finally in local government. The policy is evaluated for its impact for three typical services, in terms of the government's ability to secure contractor interest in tendering. Success has been mixed, and government efforts to stimulate contractor interest have had a marginal impact. Substantial cost savings can be made from market testing, but management should be left to choose which support services are subject to the discipline of the market.
Sustainable Urban Transport Systems: An Expert-based Strategic Scenario Approach
Authors: Nijkamp Peter , Ouwersloot Hans , Rienstra Sytze A.
Published: July 2002

Current trends in transport indicate that the system is moving away from sustainability and that major changes are necessary to make the transport system more compatible with environmental sustainability. Main problems may occur in urban transport, where not many promising solutions are expected, while the problems are severe. In view of the great number of uncertainties, we will in our paper resort to the use of scenarios. We will address in particular expert scenarios, concerned with a sustainable transport system, by applying the recently developed spider model. Based on a set of distinct characteristics, represented in eight axes in the spatial, institutional, economic and social-psychological field, an evaluation framework is constructed which visualises the driving forces that largely influence the future of the urban transport system. Next, expected and desired scenarios are constructed on the basis of information obtained from a survey among Dutch transport experts (both average scenarios and scenarios reflecting segments of respondents). The expected scenarios show that many current trends will continue, while the transport system is largely the same as the current one. The desired scenarios on the other hand, suggest the emergence and the need for a more collective system, in which also many new modes are operating. In the paper the resulting urban transport systems are also discussed. By calculating the CO2 emissions in the average expected and desired scenario, we can test the fulfilment of environmental quality norms. It appears that the expected scenario does not lead to a significant reduction of those emissions; the desired scenario however, may lead to a large scale reduction of the emissions. The conclusion is that the differences in expert opinion are small and that a sustainable (urban) transport system is still far away in the future, although the compact city concept may perhaps offer a promising perspective.
Space to Grow Old In: The Availability of Public Spaces for Elderly Persons in Singapore
Authors: Teo Peggy
Published: July 2002

Using a political economy approach, this paper examines the provision of facilities and services for elderly persons in urban Singapore. It posits that policies concerning this group are socially constructed and that ageist notions affect the spatial forms created for meeting the health, housing and social needs of older people. It emphasises the significance of subjectivity in the environmental strategies of older persons and investigates the extent to which state provisions incorporate the concept of personal geographies. It concludes that rethinking by the state is necessary to prevent the artificial separation of the spaces in which elderly people conduct their everyday activities, a need which is tenable because of the limited amount of space available in the country.
Empirical Analysis of Work Schedule Flexibility: Implications for Road Pricing and Driver Information Systems
Authors: Emmerink Richard H. M. , van Beek Paul
Published: July 2002

This paper gives an empirical analysis of work start time decisions. This issue is highly relevant for the future implementation of both road pricing and driver information systems, as flexibility in terms of work schedules for a sufficiently large number of travellers is an important condition to render successful the implementation of road pricing schemes and driver information systems. The analysis in the paper focuses on: the factors that determine the work schedule flexibility; the level of satisfaction derived from the actual work start time; and the amount of flexibility (allowed for by both the employer and the employees themselves) in the work start time. The paper concludes by discussing the implications of the empirical findings for the implementation of road pricing schemes and driver information systems.
The Repair and Maintenance of Properties in Mixed Ownership: A Study of House-factoring in Glasgow
Authors: Sim Duncan
Published: July 2002

The paper explores issues of repair and maintenance in properties in mixed ownership, focusing in particular on the Scottish practice of' 'factoring'.Factors have traditionally had a poor image, perhaps because of previous connections with private landlords, and they are often accused of poor management. This paper explores the contrasting roles and attitudes of factors and owners in the maintenance of property and suggests that the factors' image is perhaps undeserved. Factors have, in the past, demonstrated an ability to think strategically about repair and to be innovative in their approach. Their actions have tended, however, to be frustrated by events and decisions outwith their control. The paper concludes by examining changes in factoring, involving housing associations and local authorities, and the challenge of CCT.
The Local Housing Sub-market Structure and Its Properties
Authors: Tu Yong
Published: July 2002

This paper gives a definition of urban owner-occupier housing sub-market structure. A dynamic stock flow approach is applied to this structure to understand its short-term equilibrium properties and long-term dynamic process. The paper concludes by investigating the connections between urban owner-occupier housing sub-market operation and some wider urban issues, with further reflections on new research directions which can provide a deeper insight into the urban system.
Are Canadian Inner Cities Becoming More Dissimilar? An Analysis of Urban Deprivation Indicators
Authors: Broadway Michael J. , Jesty Gillian
Published: July 2002

The dominant paradigms in contemporary Canadian inner-city research have been documenting the influx of well-educated professionals into select inner-city neighbourhoods and the distinctiveness of Canadian cities from their US counterparts. These approaches have ignored the role of structural economic change in producing high levels of unemployment as manufacturing jobs have left the inner city. This paper measures the relative strength of these opposing forces within the Canadian urban system by examining changes in inner-city deprivation levels between 1981 and 1991 for the 22 largest cities. The study found evidence of increasing divergence in deprivation levels at the inter-city and intra-city levels but these could not be attributed to structural economic change; instead, local factors appear to be major determinants of overall inner-city conditions.
The Enabling Local State and Urban Development: Resources, Rhetoric and Planning in East London
Authors: Rydin Yvonne
Published: July 2002

Current literature on the new urban governance highlights the changes in patterns of relationships between actors at the local level, but also emphasises the continuing or even increasing importance of central government; in urban policy in particular there has been notable centralisation. Using a case study of urban regeneration within the Thames Gateway area of London, the paper examines the locus of power in the relationships between central and local government and the key economic interests; this allows a reappraisal of the claims of the local authority to be enabling development. The paper then turns to the language of enabling as found in policy and academic literature and argues both that changes in the language of policy have been distinctive and that this is actively contributing to the new urban governance. This analysis is grounded in a framework for considering the relationship of language to the policy process, proposing a rhetorical methodology of policy discourse analysis.
Why People Move to the 'Sun-belt': A Case Study of Long-distance Migration to the Gold Coast, Australia
Authors: Stimson Robert J. , Minnery John
Published: July 2002

This paper reports a study investigating long-distance migration to the Gold Coast in Australia's 'sun-belt'. A survey of in-migrant households, derived through a random digit dialling sample and telephone interviewing, collected data on aspects of the migration decision process. The data show non-economic, mainly lifestyle factors to be predominant in migration decisions. The relationships amongst employment status, housing tenure and household/family structure were investigated and changes as a result of migration were identified. While the majority of migrants are satisfied with their relocation to the 'sun-belt', 30 per cent of migrants were contemplating further long-distance migration, including return migration. The study also confirms the need for migration studies to look beyond the traditional form of push-pull factors as a theoretical framework.
Measuring Optimal Population Distribution by Agglomeration Economies and Diseconomies: A Case Study of Tokyo
Authors: Zheng Xiao-Ping
Published: July 2002

This paper presents an empirical study on the optimality of population distribution within the Tokyo metropolitan area. By taking into account the effects of agglomeration economies and diseconomies on the urban business firms' and households' behaviour, a benefit function and a cost function are obtained that are dependent on the distribution of urban population. Using statistical data from the Tokyo metropolitan area, estimates are made of these agglomeration-related benefit and cost functions, and the related population density functions as well. A comparison between the estimated benefit and cost functions shows that the distribution of population is optimal around the central and peripheral cities but non-optimal in between them, and the global city size of the whole area is optimal.
Is It Possible to Build Financially Successful New Towns? The Milton Keynes Experience
Authors: Peiser Richard B. , Chang Alain C.
Published: July 2002

The last generation of British new towns is being completed with the dissolution of the New Towns Development Corporations. As the final chapter of the new town movement in Britain draws to a close, this paper examines their financial success by focusing on Milton Keynes. Reputedly one of the most successful new towns, Milton Keynes was the last new town to be started and had the largest projected population. The paper examines the financial accounting reports from 1971 to 1993 and computes the economic returns for the new town as a whole and for each of the major property types. We find that Milton Keynes lost more than one-half a billion pounds. The paper explores why this happened and what the lessons are for new town development efforts around the world. The paper concludes that while it is possible to develop financially successful new towns, it is extremely difficult.
Effective Housing Demand in Mumbai (Bombay) Metropolitan Region
Authors: Tiwari Piyush , Parikh Kirit , Parikh Jyoti
Published: July 2002

Housing policy formulation should be informed by a careful understanding of the behaviour of the urban housing market, as reflected by housing demand behaviour. Such basic information is important, not only for improved project design but also for the development of better sector-wide policies. The overall analysis in this paper stresses the importance of prices and income on the demand for housing in Mumbai metropolitan region. Estimates of housing demand function are given. In our analysis, we account for rent control in Mumbai which distorts rents. The results indicate that housing demand is elastic with respect to income and price. The income and price elasticities are around 1 and — 1 respectively. We also estimate income and price elasticities for different income classes. The paper concludes with policy prescriptions.
Estimating Market Prices and Assessed Values for Income Properties
Authors: Janssen Christian , Söderberg Bo
Published: July 2002

Assessors perform property valuations for the purpose of tax assessment. Buyers and sellers make investment decisions culminating in a market price. The valuation by assessors is supposed to be fair and equitable and to amount to a prescribed proportion of market value. We investigate the property features considered by assessors in arriving at the assessed value, and by buyers and sellers in arriving at the market price. We also explore what factors appear to be considered differently by the assessors and the market thus contributing to overassessment or underassessment of property taxes. The analysis deals with income properties centrally located in Stockholm, Sweden.
The Discourse of 'Community' and the Reinvention of Social Housing Policy in Australia
Authors: Darcy Michael
Published: July 2002

Recent developments in Australian social housing policy encompass a larger role for non-government housing providers. The new emphasis is mediated and supported by the discourse of 'community' housing. 'Community' is invoked as an ideal by liberal critics of the centralised state, and conversely, by critics of liberalism who pose it as an alternative to individualism and the abstract formalism of the liberal state. Much of the rhetoric of community housing in Australia has emphasised its claimed potential to demonstrate ways in which social housing management can be made more accountable and responsive, as well as more equitable and efficient, but the evident contradictions in the discourse raise questions concerning the reasons for, and likely outcomes of, state sponsorship of community housing. This paper employs 'textually oriented discourse analysis' to examine key policy documents which have informed the development of community housing policy in Australia, and demonstrates linkages between these discourse samples, and the international tendencies in the societal order of discourse identified by Fairclough as 'democratisation', 'commodification' and 'technologisation'.
Applying developmental science in the 21st century: International scholarship for our times
Authors: Lerner Richard M. , Fisher Celia B. , Weinberg Richard A.
Published: July 2002

Applied developmental science (ADS) is scholarship that seeks to advance the integration of developmental research with actions that promote positive development and/or enhance the life chances of vulnerable children, youth, young and old adults, and their families. The ADS perspective challenges the validity of decontextualised knowledge and the legitimacy of isolating scholarship from the pressing human problems of our world. This orientation emphasises the importance of scholar/university-community partnerships as an essential means of fostering bidirectional relationships between research and practice, wherein developmental research both guides and is guided by the outcomes of social interventions.
Examining relations between shame and personality among university students in the United States and Japan: A developmental perspective
Authors: Crystal David S. , Parrott W. Gerrod , Okazaki Yukiko , Watanabe Hirozumi
Published: July 2002

American and Japanese university students’ shame (haji)-related reactions across a number of diverse situations, and the personality correlates of these reactions, were studied. With age, shame ratings decreased significantly in situations describing defects in the “private selffiamong American students, and haji ratings decreased significantly in situations in which the “public selffiwas ridiculed or discomforted among Japanese students. Also with age, individual differences in personality, particularly internal self-introspection, played an increasingly important role in predicting shame reactions among American students, whereas among Japanese students, individual personality differences became increasingly unimportant in determining haji-related phenomena. Finally, American students showed an increasing, and Japanese students a decreasing, integration of internal- and external-oriented elements of personality with development. Results are discussed in terms of theories of emotional development and cultural differences in self-concept.
Genetically Informative Designs for the Study of Behavioural Development
Authors: Lemery Kathryn S. , Goldsmith H. Hill
Published: July 2002

Genetic and environmental influences on behaviour and development can be examined by studying more than one individual within a family, using quantitative genetic theory and behavioural genetic (BG) methodology. Specific environmental and genetic influences can be measured and effect sizes estimated, and many assumptions of the methodology can be explicitly tested. BG designs can identify specific aspects of the environment that have the greatest influence on behavioural variation, and they can pinpoint critical periods in which environmental influences are most malleable, both of which are useful when designing interventions. Traits that are shown to be the most heritable through traditional family resemblance methods can now be explored further and actual genes may be identified, using new molecular methods. By identifying specific genetic and environmental influences on behaviour, and modelling the structure of these influences over time, we can rapidly advance our understanding of human development.
Motivational Conflict and Prosocial Behaviour of Kindergarten Children
Authors: Trommsdorff Gisela , Friedlmeier Wolfgang
Published: July 2002

The present study aims to clarify the role of different emotions for children’s prosocial behaviour on the basis of a motivation-theoretical approach. Specifically, the functions of empathy and distress with respect to prosocial behaviour were investigated in two different experimental situations. Five-year-old girls ( N = 50) participated in two observation studies. In study 1 the girls were randomly assigned: (a) to a nondistraction condition by experiencing another person’s misfortune ( N = 13); or (b) to a distraction condition by inducing achievement motivation. In study 2 the girls ( N = 25) underwent the same procedure as in the nondistraction condition in order to check the cross-validation of the variables measured. The girls’ videotaped nonverbal reactions (quality of facial expression and focus of attention) as well as the intensity of helping were analysed. The cross-validation was successful. The two experimental conditions did not differ with respect to empathy, distress, and helping. However, the relation between empathy and distress pointed at different directions with regard to the results of the two experimental groups. Furthermore, the positive effect of empathy as well as the negative effect of distress on prosocial behaviour were eliminated in case of the distraction situation. The measures on focus of attention supplemented the understanding of these different reactions in the two experimental conditions. The results are discussed in a motivation-theoretical framework by taking into account processes of emotion regulation.
Cognitive and Behavioural Development of Israeli Males with Fragile X and Down Syndrome
Authors: Burack Jacob A. , Shulman Cory , Katzir Esther , Schaap Tamar , Brennan Julie M. , Iarocci Grace , Wilansky Pamela , Amir Naomi
Published: July 2002

Hebrew translations of the Kaufman Assessment Battery for Children (KABC) and the Vineland Adaptive Behaviour Scales (VABS) were administered to 17 Israeli males with fragile X and 17 with Down syndrome matched for chronological and mental ages. When differences in the initial baselines were considered, the pattern of findings was generally consistent with previous reports. On the K-ABC, the males with fragile X scored higher on some subtests of the Simultaneous Domain but not on any of those of the Sequential Domain. On the VABS, superior scores of the males with fragile X on the Daily Living Skills and Communication domains is consistent with prior evidence of their relative strength on the former and the specific weakness of persons with Down syndrome on the latter. These differences between the males with fragile X and Down syndrome with regard to functioning on various domains and subdomains highlight the need to carefully examine the profiles of aetiologically homogeneous groups of persons.
MNE Supply Linkages and the Local SME Sector: Evidence from Yorkshire and Humberside
Authors: Crone M. , Watts H. D.
Published: July 2002

This paper draws on evidence from a new survey of large MNE-owned manufacturing plants in Yorkshire and Humberside and questions the expectation that MNE plants will stimulate the local SME sector though local sourcing of material and component inputs. MNE plants in Yorkshire and Humberside sourced less than 25 percent of their material and component inputs from the local region and less than two percent from local SMEs. Smaller MNE plants were more likely to source from local SMEs as were MNE plants searching for low technology inputs, in sectors such as mechanical engineering and metal goods. MNE plants in the chemicals and motor vehicle component sectors had few local SME suppliers
The Other Crisis
Authors: Gaffikin Frank , Morrissey Mike
Published: July 2002

This article critically reviews the most recent economic development strategy for Northern Ireland, Strategy 2010. It is discussed within the con text of more general approaches to region al development and in terms of questioning whether it is adequate to address the key structural weaknesses of the local economy. The judgement is that it represents a superior approach to previous economic development strategies, but remains weak in integrating social inclusion objectives into the economic development process, underestimates the potential for developing economic relationships with the Irish Republic and fails to acknowledge that community division remains a barrier to successful development.
The Drive to Codify: Implications for the Knowledge-based Economy
Authors: Roberts Joanne
Published: July 2002

This paper critically explores the forces driving the codification of knowledge, together with the implications of codification for the evolution of the knowledge-based economy. It is argued that tacit knowledge is neglected in the drive to codify with important consequences for the process of knowledge creation and innovation. The drive to codify knowledge is briefly considered in the context of higher education and then through the practice of knowledge management within firms. The paper is exploratory in nature and seeks to outline policy concerns and directions for further research.
Observational Batteries in Neurotoxicity Testing
Authors: Moser Virginia C.
Published: July 2002

Behavioral evaluations are emerging as a key component in neurotoxicity testing. A neurobehavioral screening battery that is most often used for hazard identification consists of a functional observational battery (FOB) and motor activity. The FOB was developed as an improvement over routine cageside observations: major differences include the specification of observations, operational definitions of the behaviors to be observed, grading the severity of effect, and location of observations (open arena vs. home cage). A typical FOB protocol consists of approximately 20 to 30 end points, allowing for the detection and description of a range of neurobehavioral changes. We have focused on assessing critical characteristics (i.e., sensitivity, specificity, validity, and reproducibility) of these tests. Concerns have been raised as to the validity and reliability of observational methods for neurotoxicity screening. These tests were therefore the focus of an international collaborative study, sponsored by the International Programme on Chemical Safety (IPCS). The purpose of the IPCS study was to assess the general utility and reliability of neurobehavioral screening procedures in a diversity of testing situations. The test protocol was essentially that described in current United States Environmental Protection Agency (US EPA) guidelines. The resultant data indicated that all participants could detect and characterize the effects of known neurotoxicants, and the divergent profiles of effect obtained for different chemicals demonstrated the specificity of the methods. One conclusion, therefore, was that behavior can be a useful tool for assessing neurotoxicity. In addition, the study also provided a wealth of control data, examination of which provides evidence for the consistency and baseline values of behavioral measures. Reliability estimates were statistically established, providing a measure of the usefulness of individual end points for detecting chemical-induced toxicity. Another conclusion of the IPCS collaborative study was that the application of these methods requires careful attention to details of experimental design, observer training, and experience; these capabilities should be adequately documented by the use of proficiency studies. Recently, modifications of the standard FOB have been introduced, including expanded clinical observations (ECO) for standard toxicity studies. Although there are end points common between the FOB and ECO, it is not known if the latter is sufficient for neurotoxicity screening. Appropriate validation studies have not been conducted on these expanded observations. With the increasing dependency on these methods for neurotoxicity testing, and the number of studies that will be incorporating these methods, issues of test validity as well as data interpretation are becoming more critical.
Relation of Apo E and ACE genes to cognitive performance in chronic alcoholic patients
Authors: BARTRéS‐FAZ D. , CLEMENTE I. C. , MONRàS M. , MUñOZ M. , LóPEZ‐ALOMAR A. , VALVENY N. , MORAL P. , GUAL A. , SáNCHEZ‐TURET M. , GUARDIA J. , JUNQUé C.
Published: July 2002

Abstract Apolipoprotein E ε 4 and ACE genes have been related to several conditions involving cognitive impairment, including Alzheimer's disease, normal ageing and cerebrovascular disease. However, it has not been established whether their genotypes are associated with alcoholism or its cognitive functioning. Genotypic distributions of 140 chronic alcoholic patients were compared with a non‐alcoholic sample, and the cognitive performance of a subsample of the alcoholic subjects was assessed with standard neuropsychological tests. No differences in allele or genotype distributions of Apo E or ACE genes were found when comparing controls and alcoholics (Apo E ε 2/2; patients 1.4%, controls 0% p < 0.06; ε 2/ε 3; patients 9.3%, controls 6.6% p < 0.29; ε 2/ε 4; patients 0%, controls 1% p < 0.31; ε 3/ε 3 patients 71.4%, controls 72% p < 0.89; ε 3/ε 4; patients 15.7%, controls 19.2%, p < 0.36; ε 4/ε 4; patients 2.1%, controls 1.2% p < 0.44; ACE D/D; patients 35%, controls 28.5% p < 0.14; I/D; patients 47.5%, controls 51.1% p < 0.51; I/I; patients 14.5%, controls 20.4% p < 0.19). In terms of cognitive performance, ε 4/ε 3 patients did better on visuoconstructive (p < 0.001) and visual memory (p < 0.04) functions compared with ε 2/ε 3 bearers. Furthermore, ACE D/D patients performed better on a test of abstract reasoning (p < 0.03) compared with the ACE I/I homozygous group. The cognitive results suggest that Apo E or ACE genotypes may modify the effects of ethanol on cognitive deterioration in alcoholic patients. However, the data do not support an association between the Apo E ε 4 allele and reduced cognitive performance in alcoholism.
A Case of RhabdomyoSarcoma Following a Metal Surgical Implant
Authors: Gatti Giovanna M. , Ivaldi Giovanni B. , Lartigau Eric , Marsiglia Hugo , Orecchia Roberto
Published: July 2002

Patient. We report a 51‐year‐old male presenting with Grade
III rhabdomyosarcoma.

Discussion. A case of rhabdomyosarcoma which developed in
proximity to a metal surgical implant is described. Few cases have been reported in
the world in humans.The therapeutic approach to the disease is presented, together
with a brief review of literature.
Phosphorylation of Myosin-Binding Subunit (Mbs) of Myosin Phosphatase by Rho-Kinase in Vivo
Authors: Kawano Yoji , Fukata Yuko , Oshiro Noriko , Amano Mutsuki , Nakamura Toshikazu , Ito Masaaki , Matsumura Fumio , Inagaki Masaki , Kaibuchi Kozo
Published: July 2002

Rho-associated kinase (Rho-kinase), which is activated by the small GTPase Rho, phosphorylates myosin-binding subunit (MBS) of myosin phosphatase and thereby inactivates the phosphatase activity in vitro. Rho-kinase is thought to regulate the phosphorylation state of the substrates including myosin light chain (MLC), ERM (ezrin/radixin/moesin) family proteins and adducin by their direct phosphorylation and by the inactivation of myosin phosphatase. Here we identified the sites of phosphorylation of MBS by Rho-kinase as Thr-697, Ser-854 and several residues, and prepared antibody that specifically recognized MBS phosphorylated at Ser-854. We found by use of this antibody that the stimulation of MDCK epithelial cells with tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor (HGF) induced the phosphorylation of MBS at Ser-854 under the conditions in which membrane ruffling and cell migration were induced. Pretreatment of the cells with Botulinum C3 ADP-ribosyltransferase (C3), which is thought to interfere with Rho functions, or Rho-kinase inhibitors inhibited the TPA- or HGF-induced MBS phosphorylation. The TPA stimulation enhanced the immunoreactivity of phosphorylated MBS in the cytoplasm and membrane ruffling area of MDCK cells. In migrating MDCK cells, phosphorylated MBS as well as phosphorylated MLC at Ser-19 were localized in the leading edge and posterior region. Phosphorylated MBS was localized on actin stress fibers in REF52 fibroblasts. The microinjection of C3 or dominant negative Rho-kinase disrupted stress fibers and weakened the accumulation of phosphorylated MBS in REF52 cells. During cytokinesis, phosphorylated MBS, MLC and ERM family proteins accumulated at the cleavage furrow, and the phosphorylation level of MBS at Ser-854 was increased. Taken together, these results indicate that MBS is phosphorylated by Rho-kinase downstream of Rho in vivo, and suggest that myosin phosphatase and Rho-kinase spatiotemporally regulate the phosphorylation state of Rho-kinase substrates including MLC and ERM family proteins in vivo in a cooperative manner.
Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells
Authors: Kleijmeer Monique , Ramm Georg , Schuurhuis Danita , Griffith Janice , Rescigno Maria , Ricciardi-Castagnoli Paola , Rudensky Alexander Y. , Ossendorp Ferry , Melief Cornelis J.M. , Stoorvogel Willem , Geuze Hans J.
Published: July 2002

Immature dendritic cells (DCs) sample their environment for antigens and after stimulation present peptide associated with major histocompatibility complex class II (MHC II) to naive T cells. We have studied the intracellular trafficking of MHC II in cultured DCs. In immature cells, the majority of MHC II was stored intracellularly at the internal vesicles of multivesicular bodies (MVBs). In contrast, DM, an accessory molecule required for peptide loading, was located predominantly at the limiting membrane of MVBs. After stimulation, the internal vesicles carrying MHC II were transferred to the limiting membrane of the MVB, bringing MHC II and DM to the same membrane domain. Concomitantly, the MVBs transformed into long tubular organelles that extended into the periphery of the cells. Vesicles that were formed at the tips of these tubules nonselectively incorporated MHC II and DM and presumably mediated transport to the plasma membrane. We propose that in maturing DCs, the reorganization of MVBs is fundamental for the timing of MHC II antigen loading and transport to the plasma membrane.
Marching at the front and dragging behind
Authors: Ballestrem Christoph , Hinz Boris , Imhof Beat A. , Wehrle-Haller Bernhard
Published: July 2002

Integrins are cell–substrate adhesion molecules that provide the essential link between the actin cytoskeleton and the extracellular matrix during cell migration. We have analyzed αVβ3-integrin dynamics in migrating cells using a green fluorescent protein–tagged β3-integrin chain. At the cell front, adhesion sites containing αVβ3-integrin remain stationary, whereas at the rear of the cell they slide inward. The integrin fluorescence intensity within these different focal adhesions, and hence the relative integrin density, is directly related to their mobility. Integrin density is as much as threefold higher in sliding compared with stationary focal adhesions. High intracellular tension under the control of RhoA induced the formation of high-density contacts. Low-density adhesion sites were induced by Rac1 and low intracellular tension. Photobleaching experiments demonstrated a slow turnover of β3-integrins in low-density contacts, which may account for their stationary nature. In contrast, the fast β3-integrin turnover observed in high-density contacts suggests that their apparent sliding may be caused by a polarized renewal of focal contacts. Therefore, differential acto-myosin–dependent integrin turnover and focal adhesion densities may explain the mechanical and behavioral differences between cell adhesion sites formed at the front, and those that move in the retracting rear of migrating cells.
Induction of secretory pathway components in yeast is associated with increased stability of their mRNA
Authors: Hyde Maureen , Block-Alper Laura , Felix Jahaira , Webster Paul , Meyer David I.
Published: July 2002

The overexpression of certain membrane proteins is accompanied by a striking proliferation of intracellular membranes. One of the best characterized inducers of membrane proliferation is the 180-kD mammalian ribosome receptor (p180), whose expression in yeast results in increases in levels of mRNAs encoding proteins that function in the secretory pathway, and an elevation in the cell's ability to secrete proteins. In this study we demonstrate that neither the unfolded protein response nor increased transcription accounts for membrane proliferation or the observed increase in secretory pathway mRNAs. Rather, p180-induced up-regulation of certain secretory pathway transcripts is due to a p180-mediated increase in the longevity of these mRNA species, as determined by measurements of transcriptional activity and specific mRNA turnover. Moreover, we show that the longevity of mRNA in general is substantially promoted through the process of its targeting to the membrane of the endoplasmic reticulum. With respect to the terminal differentiation of secretory tissues, results from this model system provide insights into how the expression of a single protein, p180, could result in substantial morphological and functional changes.
Constitutive Expression of Interleukin (IL)-4 In Vivo Causes Autoimmune-type Disorders in Mice
Authors: Erb Klaus J. , Rüger Beate , von Brevern Maja , Ryffel Bernhard , Schimpl Annelise , Rivett Karen
Published: July 2002

The transgenic (tg) expression of interleukin (IL)-4 under the control of a major histocompatibility complex (MHC) class I promoter leads to B cell hyperactivity in mice, characterized by increased B cell surface MHC class II and CD23 expression, elevated responsiveness of the B cells to polyclonal ex vivo stimulation, and increased immunoglobulin (Ig)G1 and IgE serum levels. Tg mice develop anemia, glomerulonephritis with complement and immune deposition in the glomeruli, and show increased production of autoantibodies. Treatment of IL-4 tg mice with anti-IL-4 neutralizing antibodies protected the mice from disease development, showing that IL-4 was responsible for the observed disorders. Deletion of superantigen responsive autoreactive T cells in the IL-4 tg mice was normal and treatment of mutant mice with deleting anti-CD4 antibodies failed to ablate the onset of autoimmune-like disease, suggesting that CD4+T cells were not the primary cause of the disorders. Furthermore, the deletion of B cells reacting against MHC class I molecules was also normal in the IL-4 tg mice. Therefore the most likely explanation for the increased production of autoantibodies and the autoimmunelike disorders is that IL-4 acts directly on autoreactive B cells by expanding them in a polyclonal manner. Taken together our results show that inappropriate multi-organ expression of IL-4 in vivo leads to autoimmune-type disease in mice.
Characterization of Human CD8+ T Cells Reactive with Mycobacterium tuberculosis–infected Antigen-presenting Cells
Authors: Lewinsohn David M. , Alderson Mark R. , Briden Andria L. , Riddell Stanley R. , Reed Steven G. , Grabstein Kenneth H.
Published: July 2002

Previous studies in murine models, including those using the β2 microglobulin knockout mouse, have suggested an important role for CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). At present, little is understood about these cells in the human immune response to tuberculosis. This report demonstrates the existence of human Mtb-reactive CD8+ T cells. These cells are present preferentially in persons infected with Mtb and produce interferon γ in response to stimulation with Mtb-infected target cells. Recognition of Mtb-infected cells by these CD8+ T cells is restricted neither by the major histocompatibility complex (MHC) class I A, B, or C alleles nor by CD1, although it is inhibited by anti–MHC class I antibody. The Mtb-specific CD8+ T cells recognize an antigen which is generated in the proteasome, but which does not require transport through the Golgi-ER. The data suggest the possible use of nonpolymorphic MHC class Ib antigen presenting structures other than CD1.
Inhibition of the B Cell by CD22: A Requirement for Lyn
Authors: Smith Kenneth G.C. , Tarlinton David M. , Doody Gina M. , Hibbs Margaret L. , Fearon Douglas T.
Published: July 2002

Mice in which the Lyn, Cd22, or Shp-1 gene has been disrupted have hyperactive B cells and autoantibodies. We find that in the absence of Lyn, the ability of CD22 to become tyrosine phosphorylated after ligation of mIg, to recruit SHP-1, and to suppress mIg-induced elevation of intracellular [Ca2+] is lost. Therefore, Lyn is required for the SHP-1–mediated B cell suppressive function of CD22, accounting for similarities in the phenotypes of these mice.
Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-Dd
Authors: Nakamura Mary C. , Hayashi Shigenari , Niemi Eréne C. , Ryan James C. , Seaman William E.
Published: July 2002

The activating Ly-49D receptor and the inhibitory Ly-49A receptor mediate opposing effects on natural killer (NK) cell cytotoxicity after interaction with the same major histocompatibility complex ligand, H2-Dd. To compare Ly-49D and Ly-49A interactions with H2-Dd, we created mutations in H2-Dd and examined the functional ability of these mutants to activate lysis through Ly-49D or to inhibit lysis through Ly-49A. Specific single amino acid changes in either the H2-Dd α1 helix or the α2 helix abrogated Ly-49D–mediated cytotoxicity, but these changes had no significant effect on Ly-49A–dependent inhibition. Each of three α2 domain mutations in the floor of the peptide binding groove reduced functional recognition by either Ly-49D or Ly-49A, but all three were required to fully abrogate inhibition by Ly-49A. Our studies indicate that Ly-49D/H2-Dd interactions require distinct determinants compared with Ly-49A/H2-Dd interactions. These differences have important implications for the integration of activating and inhibitory signals in NK cells.
Legionella pneumophila Replication Vacuoles Mature into Acidic, Endocytic Organelles
Authors: Sturgill-Koszycki Sheila , Swanson Michele S.
Published: July 2002

After ingestion by macrophages, Legionella pneumophila inhibits acidification and maturation of its phagosome. After a 6–10-h lag period, the bacteria replicate for 10–14 h until macrophage lysis releases dozens of progeny. To examine whether the growth phase of intracellular L. pneumophila determines the fate of its phagosome, interactions between the endosomal network and pathogen vacuoles were analyzed throughout the primary infection period. Surprisingly, as L. pneumophila replicated exponentially, a significant proportion of the vacuoles acquired lysosomal characteristics. By 18 h, 70% contained lysosomal-associated membrane protein 1 (LAMP-1) and 40% contained cathepsin D; 50% of the vacuoles could be labeled by endocytosis, and the pH of this population of vacuoles averaged 5.6. Moreover, L. pneumophila appeared to survive and replicate within lysosomal compartments: vacuoles harboring more than five bacteria also contained LAMP-1, inhibition of vacuole acidification and maturation by bafilomycin A1 inhibited bacterial replication, bacteria within endosomal vacuoles responded to a metabolic inducer by expressing a gfp reporter gene, and replicating bacteria obtained from macrophages, but not broth, were acid resistant. Understanding how L. pneumophila first evades and then exploits the endosomal pathway to replicate within macrophages may reveal the mechanisms governing phagosome maturation, a process also manipulated by Mycobacteria, Leishmania, and Coxiella.