bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a performance appraisal training program for the Rehabilitation Institute of Chicago
Authors: Kilgore Ford Deborah
Published: August 2004

“Nobody w ants to get one. Nobody wants to give one.” The problem was that the supervisors and managers of the Rehabilitation Institute of Chicago (RIC) did not know how to use the Institute's new performance management system and had not been trained on how to prepare and deliver effective performance appraisals. The problem further included the fact that RIC was required to improve its effectiveness and timeliness with performance appraisals in preparation for its 2002 Joint Commission on Accreditation of Healthcare Organizations (JCAHO) review and felt bound to be timely for its employees as sound management practice. The research question was: “What should be contained in a training program for effective performance appraisals that drives performance accountabilities in a mutually satisfying way for adults who can find themselves as either appraisees or appraisers?” Procedures to develop a performance appraisal training program included a review of the literature, selection of formative and summative committee members, and design and validation of criteria and contents of a performance appraisal training program. The results of the study included the creation of a two‐module performance appraisal training program that included a module on the new performance management system contents and the manager's role within that system, and a module on preparing, delivering and assessing effective performance appraisal experiences. The conclusions reached included that it was possible to design a performance appraisal training that incorporated adult learning principles including learner‐centered strategies that also reinforced ownership of timeliness. Face‐to‐face training experiences were augmented by online training materials, allowing for access by 20 RIC locations. RIC has approved recommendations for further evaluation of the effectiveness of the performance appraisal system. Recommendations to apply adult learning principles to internal adult learning venues have received broader acceptance within the wider management and employee groups.
Self‐interest and scholarly publication: the dilemma of researchers, reviewers, and editors
Authors: Calabrese Raymond L. , Roberts Brian
Published: August 2004

Academic misconduct in research is of growing concern to funding agencies, scholars, and academic journal editors. Scholarly publication has ethical implications researchers, reviewers, and journal editors. The theoretical background of the ethics of scholarly publication is explored as well as the use of a case study of an untenured researcher illustrates the dilemma faced by the researcher's colleagues, reviewers, and the journal editor. It also explores how the higher education culture promotes a “publish or perish” environment that impacts the behavior of faculty seeking tenure and promotion.
Critical evaluation of the impact of global educational reform: an Irish perspective
Authors: Donnelly Roisin
Published: August 2004

Global trends in the new public management (NPM) of education have manifested themselves differently in different countries. Its manifestation, the significant issue that this paper addresses, is whether it has led to any changes in education in the third level sector in the Republic of Ireland in the last 10 years. This will be achieved through a critical exploration of the expression of higher educational reform worldwide, and a review of its impact on higher education (HE) in Ireland. Within this, there are a number of specific objectives: to discuss the context of HE (including policy issues and stakeholders) in the Republic of Ireland; to summarise the main trends of NPM in HE; to critically evaluate the concept of educational reform, and through an articulation of a theoretical framework, explore this growing global trend and examine whether Irish HE is developing in a similar direction.
Reasons to remain in college: a comparison of high school and college students
Authors: Mayo Donna T. , Helms Marilyn M. , Codjoe Henry M.
Published: August 2004

Retaining students is a critical topic in higher education. A plethora of research has investigated demographic, age, life stage, ethnicity, and a host of other variables that influence retention. Colleges have responded to retention issues with a host of classes, workshops, and orientation or mentoring programs to aid student retention. Specifically, this study compares the retention concerns of high school students considering college vs the concerns of existing college students in a variety of degree programs to see if factors vary over time. Using a case study approach, the study found three key variables associated with retention problems. The discussion and conclusions identify ways for colleges to alter both marketing and assistance programs for both groups. Suggestions for replication and areas for future research as well as implications for policy directions are included.
Budgetary practices and accountability habitus
Authors: Goddard Andrew
Published: August 2004

This paper is the first of several emanating from a study of the relationship between accounting, governance and accountability in local government in the UK. A grounded theory methodology was used to discover participants' perceptions of these phenomena in four UK local government organisations. The budget system was found to be the most important organizational process with respect to accountability and this paper focuses on the core relationship discovered between budgetary practices and accountability perceptions. The way in which accountability was perceived and the budgetary practices were quite distinct in each of the four case studies. A grounded theory of this relationship is developed from the case studies to explain these differences. Bourdieu's concept of habitus is used to further develop this grounded theory and to suggest a more formal theory.
Accounting and the holocausts of modernity
Authors: Neu Dean , Graham Cameron
Published: August 2004

The current study explores the ambiguity of accounting technique in the context of a historical study of the Canadian Indian Department under the direction of Deputy Superintendent D.C. Scott at the beginning of the 20th century. Starting from the work of Bauman and his commentators, we argue that modernity viewed as a set of practices and thought patterns, facilitates bureaucratic constructions of the “Indian problem” In turn, this cultural milieu and bureaucratic construction operated as an ideological circle, encouraging the use of accounting techniques of governance that permitted both the distancing of bureaucrats from indigenous peoples and the downplaying of other vantage points. However, as our analysis highlights, numerical re‐presentations also provided the tools and rhetorical spaces for challenges to government policy.
How successfully does JIT handle machine breakdowns in an automated manufacturing system?
Authors: Özbayrak Mustafa , Cagil Gultekin , Kubat Cemalettin
Published: August 2004

Scheduling a manufacturing system can be one of the most complex tasks in managing an operation. Planning and control systems such as just in time (JIT) can aid scheduling. However, planning and control tools require a fairly stable shopfloor environment to get the best out of them. Many system designs and schedules only consider 100 per cent reliability in machines, and do not take into account random interruptions. In this paper, a simulation model was created to investigate machine and material handling system breakdown problems in a JIT‐driven flexible manufacturing system. Results show that compromises have to be made with JIT control in order to get the best system performance.
Customer requirement constructs: the premise for TQM in education
Authors: Sahney Sangeeta , Banwet D.K. , Karunes S.
Published: August 2004

Amidst the tremendous pressures faced by educational institutions, both from internal as well as from external forces, the higher educational institutions in India, as elsewhere in the world, have begun to understand and accept the significance of customer‐centered philosophies, with the answer to such pressures being in “delighting the customer”, which is the rule for survival in the long run. “Delighting the customer”, is one of the core elements of total quality management (TQM), which emphasizes the service relationship between an organization/institution and its customers. A number of success stories about incorporating TQM principles in the educational setting have been reported. In TQM, the focus is on the customer. Ultimately, the objective of TQM is to build an institution that produces products or performs services, which fulfill customer requirements, and thereby delights them. Such customer requirements thus, form the very premise for TQM. So it is important not only to identify the numerous and varied customers of the educational system, but also to identify their requirements and satisfy them. The importance/degree assigned to such requirements or their constructs may vary across customer groups and also amongst the institutions themselves. The paper presents the results of an empirical study conducted on select higher educational institutions to assess the importance/degree assigned to the various customer requirement constructs across the various internal and external customer groups. Starting with a theoretical background, an empirical study is presented with analysis and results.
Educational modelling language: modelling reusable, interoperable, rich and personalised units of learning
Authors: Koper Rob , Manderveld Jocelyn
Published: August 2004

Nowadays there is a huge demand for flexible, independent learning without the constraints of time and place. Various trends in the field of education and training are the bases for the development of new technologies for education. This article describes the development of a learning technology specification, which supports these new demands for learning challenging the new technological possibilities. This specification is named Educational Modelling Language (EML) and is developed by the Open University of the Netherlands.
Subtle intracorneal findings in inflammatory disorders: hyphae or not?
Authors: Szabo Sarolta K. , Jaworsky Christine
Published: August 2004

Background:  Spongiotic and lichenoid dermatitides are frequently stained with periodic acid‐Schiff (PAS) stains to check for the presence of dermatophytes. PAS+ structures without a septate morphology are often seen with lichenoid dermatitides, however, their nature has not been previously characterized.

Methods:  Fifteen consecutive biopsies of lichenoid and five spongiotic dermatitides were stained with hematoxylin and eosin (H&E), PAS, and antibodies to CD1a.

Results:  Twelve of 15 lichenoid and none of the five spongiotic dermatitis showed PAS+ structures in the stratum corneum. Distinct septation or branching was not identified in these PAS+ structures. Eleven of 15 from the lichenoid group, but none from the spongiotic group, showed CD1a+ structures in the stratum corneum. This staining pattern suggests that the intracorneal structures represent the dendritic processes of Langerhans' cells (LCs) within the stratum corneum.

Conclusions:  PAS+ and CD1a+ structures are present in the stratum corneum of lichenoid, but not in spongiotic, dermatitis. This study morphologically confirms extension of LC dendrites into the stratum corneum in lichenoid but not in spongiotic dermatitides.
Human herpesvirus‐8 is not associated with angiolymphoid hyperplasia with eosinophilia
Authors: Bhattacharjee Pradip , Hui Pei , McNiff Jennifer
Published: August 2004

Background:  Angiolymphoid hyperplasia with eosinophilia (ALHE) is an angioproliferative lesion, typically consisting of single or multiple red papules or nodules in the head and neck region. The etiology of ALHE, whether reactive or neoplastic, is unclear. It has been well documented in the literature that human herpesvirus‐8 (HHV‐8) DNA is present in the majority of cases of Kaposi's sarcoma; however, there is contradictory data regarding the association of this virus with ALHE.

Methods:  We performed immunohistochemical studies for HHV‐8 on paraffin‐embedded tissue from 23 cases of histologically confirmed ALHE. Polymerase chain reaction (PCR) analysis for HHV‐8 DNA was performed on 14 of the 23 cases that had adequate remaining tissue for the procedure. The results of the immunohistochemical studies and PCR analysis were compared.

Results:  HHV‐8 immunohistochemical studies were negative in all 23 cases of ALHE. PCR‐based analysis on 14 cases failed to identify HHV‐8 DNA.

Conclusions:  Combined data from several, small published studies are equivocal for an association between HHV‐8 and ALHE. The results of our large study show no association between HHV‐8 and ALHE.
The De Barsy syndrome
Authors: Guerra Deanna , Fornieri Claudio , Bacchelli Barbara , Lugli Licia , Torelli Paola , Balli Fiorella , Ferrari Paola
Published: August 2004

Background:  In 1968, De Barsy reported on a girl exhibiting an aged aspect, ‘dwarfism, oligophrenia, and degeneration of the elastic tissue in cornea and skin’. The disorder was recognized as a subgroup of cutis laxa syndrome and termed De Barsy–Moens–Dierckx syndrome. The pathogenesis of the disorder is unknown.

Methods:  To improve the comprehension of the pathogenetic mechanisms involved in the De Barsy syndrome, we performed an ultrastructural, morphometric, immunocytochemical study on a skin biopsy of a boy with the De Barsy phenotype, who has been clinically followed for 12 years from birth. Moreover, the lysyl oxidase activity was measured on skin fibroblasts cultured in vitro.

Results:  Light and electron microscopy, morphometry, and immunocytochemical observations showed a significant reduction of the elastic fibers in the papillary and in the reticular dermis of patient compared to an age‐matched control (p < 0.05). By contrast, the collagen structure, content, and the distribution were normal, as well as lysyl oxidase activity in the medium of in vitro fibroblasts (12,323 DPM/106 cells). The immunoreaction for antibodies recognizing fibrillin‐1, neutrophilic elastase, and tumor necrosis factor‐α was stronger, whereas that for antibodies against transforming growth factor‐β was less pronounced in the dermis of the De Barsy boy compared to control.

Conclusions:  Clinical, phenotypic, and structural data were consistent with the diagnosis of De Barsy syndrome. This is the first case described in Italy. Clinical and structural data confirm that the elastic component is mostly affected in this disorder. Moreover, ultrastructural and immunochemical findings suggest that both elastic fiber degradative and very likely synthetic processes are involved.
Competition and Information Production in Market Maker Models
Authors: Morrison Alan D.
Published: August 2004

Abstract:  The microstructure literature models the mechanisms through which fundamental information is incorporated into market prices. This paper extends previous models by endogenising information production and analysing incentives for costly information production. In contrast to the existing literature, increasing the number of informed traders can result in reduced price informativeness. When prices have an allocative role this has welfare consequences: the regulatory implications of a dichotomy between private and public incentives for information gathering are discussed.
Debt Overhang, Costly Expandability and Reversibility, and Optimal Financial Structure
Authors: Jou Jyh‐Bang , Lee Tan
Published: August 2004

Abstract:  This article compares the investment and financing decisions of a firm that adopts a ‘first‐best’ strategy with those of a firm that adopts a ‘second‐best’ strategy. The former issues bonds upon deciding an initial capacity, while the latter issues bonds, and only then decides an initial capacity. The former is thus able to avoid the agency cost associated with the ‘debt overhang’ problem. Accordingly, the former will both issue more bonds and install a larger initial capacity than the latter. However, the agency cost of debt, i.e., firm value difference between these two strategies, is modest for plausible parameter values.
Emotional and Behavioral Consequences of Bioterrorism: Planning a Public Health Response
Authors: STEIN BRADLEY D. , TANIELIAN TERRI L. , EISENMAN DAVID P. , KEYSER DONNA J. , BURNAM M. AUDREY , PINCUS HAROLD A.
Published: August 2004

Millions of dollars have been spent improving the public health system's bioterrorism response capabilities. Yet relatively little attention has been paid to precisely how the public will respond to bioterrorism and how emotional and behavioral responses might complicate an otherwise successful response. This article synthesizes the available evidence about the likely emotional and behavioral consequences of bioterrorism to suggest what decision makers can do now to improve that response. It examines the emotional and behavioral impact of previous “bioterrorism‐like” events and summarizes interviews with experts who have responded to such events or conducted research on the effects of communitywide disasters. The article concludes by reflecting on the evidence and experts' perspectives to suggest actions to be taken now and future policy and research priorities.
A Communitywide Intervention to Improve Outcomes and Reduce Disability among Injured Workers in Washington State
Authors: WICKIZER THOMAS M. , FRANKLIN GARY M. , MOOTZ ROBERT D. , FULTON‐KEHOE DEBORAH , PLAEGER‐BROCKWAY ROY , DRYLIE DIANA , TURNER JUDITH A. , SMITH‐WELLER TERRI
Published: August 2004

One pressing challenge facing the U.S. health care system is the development of effective policies and clinical management strategies to address deficiencies in health care quality. In collaboration with researchers at the University of Washington, the Washington State Department of Labor and Industries has created a communitywide delivery system intervention to improve health outcomes and reduce disability among injured workers. This intervention is currently being tested in two sites in western and eastern Washington. So far, it appears to be possible to engage physicians and health care institutions in quality improvement initiatives and to form effective public‐private partnerships for this purpose. Furthermore, collaborating with university researchers may help enhance the scientific rigor of the quality improvement initiative and create more opportunities for a successful evaluation.
Cross‐National Concepts in Supranational Governance: State–Society Relations and EU Policy Making
Authors: Yee Albert S.
Published: August 2004

The emergence of multiple and shifting modes of governance both intranationally and supranationally has posed difficulties for analysts accustomed to refining or testing singular types of politics. When confronted with this changing complexity, a comprehensive framework can be a very useful diagnostic and organizational tool. This article devises one such conceptual framework to clarify and systematize varieties of state autonomy and state–society relations. By combining fundamental conceptions of action, elemental control mechanisms, and basic types of interaction, a comprehensive framework is constructed for characterizing and comparing governance modes in a conceptually coherent manner. Many of the abstract spaces within this conceptual field share affinities with types of state autonomy and state–society relations depicted in major theoretical approaches to national politics (i.e., authoritarianism, statism, pluralism, corporatism, institutionalism, and Marxism). This article uses this conceptual framework to systematize these major governance modes and to illuminate their coexistence in supranational governance by examining the European Union policy process.
Wetland Vegetation Response to the Restoration of Sheet Flow at Cheyenne Bottoms, Kansas
Authors: Kindscher Kelly , Aschenbach Todd , Ashworth Sharon M.
Published: August 2004

The restoration of inland salt‐affected plant communities, including saltflat mixed prairie and playa lakes wetlands, has received little attention despite the importance of these communities for critical wildlife habitat. The salt‐affected communities of Cheyenne Bottoms, located in central Kansas, are a crucial stopover site for migratory waterfowl and shorebirds. In 1998, The Nature Conservancy attempted to restore native plant communities to grazed and former cropland at Cheyenne Bottoms by reestablishing sheet flow across these disturbed areas. We collected vegetation cover data along permanent transects established in rangeland, former cropland, and in a shallow basin 3 years (1996–1998) before the hydrological changes and continued to collect vegetation data for 3 years (1999–2001) after the hydrological changes. Vegetation composition changes in response to the restored hydrology were subtle, but the average wetland index along the transects in the basin and the rangeland significantly declined. Significant decreases occurred in the cover of perennials and graminoids in both spring and fall species assemblages of the rangeland area. Changes in the former cropped areas were mixed, indicating the difficulty of restoring these disturbed plant communities to native plant assemblages within a few years.
Monitoring an Arizona Ponderosa Pine Restoration: Sampling Efficiency and Multivariate Analysis of Understory Vegetation
Authors: Abella Scott R. , Covington W. Wallace
Published: August 2004

As monitoring plans for the restoration ofPinus ponderosaforests in the southwestern United States evolve toward examining multifactor ecosystem responses to ecological restoration, designing efficient sampling procedures for understory vegetation will become increasingly important. The objective of this study was to compare understory composition and diversity among thin/burn and control treatments in aP. ponderosarestoration, while simultaneously examining the effects of sampling design and multivariate analyses on which conclusions were based. Using multi‐response permutation procedures (MRPP), we tested the null hypothesis of no difference in understory species composition among treatments using different data matrices (e.g., frequency and cover) for two different sampling methods. Treatment differences were subtle and were detected by an intensive 50, 1‐m2subplot sampling method for all data matrices but were not detected by a less intensive point‐intercept sampling method for any matrix. Sampling methods examined in this study controlled results of multivariate analyses more than the data matrices used to summarize data generated by a sampling method. We partitioned data into plant life form and native/exotic species categories for MRPP, and this partitioning isolated plant groups most responsible for treatment differences. We also examined the effects of number of 1‐m2subplots sampled on mean‐species‐richness/m2estimates and found that estimates based on 10 subplots and based on 50 subplots were highly correlated (r = 0.99). Species–area curves indicated that the 50, 1‐m2subplot sampling method detected the common species of sites but failed to detect the majority of rare species. Additional sampling‐design studies are needed to develop single sampling designs that produce multifactor data on plant composition, diversity, and spatial patterns amenable to multivariate analyses as part of monitoring plans of vegetation responses to ecological restoration.
Odonates as Indicators of Shallow Lake Restoration by Liming: Comparing Adult and Larval Responses
Authors: D'Amico F. , Darblade Stéphanie , Avignon S. , Blanc‐Manel Stéphanie , Ormerod S. J.
Published: August 2004

Odonate assemblages were compared between replicate sets of shallow lakes that had been created and acidified by open‐cast mining across a large area (2,451 ha) of southwest France (Arjuzanx, Landes); one set of lakes (n = 5) was experimentally restored by liming with calcium carbonate, whereas another group (n = 5) was left as untreated reference lakes. Both odonate adults and exuviae were sampled bimonthly during May–August 1998. Elevated turbidity and conductivity in limed lakes were the only physicochemical measures differing between restored and reference lakes, because deacidification occurred naturally, even in reference lakes during the 17 years after the onset of restoration. Restoration by liming can apparently lead to effects on lake turbidity that might be considered adverse. Twenty‐four and 19 odonate species occurred among adults and exuviae, respectively, but there were no significant differences in richness between restored and reference sites. However, significantly, more exuviae were collected from the reference sites (588 vs. 180), where exuvial diversity and rank abundance indicated more evenly structured assemblages than those in restored lakes. Ordination showed that adult assemblages differed significantly between restored and reference lakes, and varied highly significantly with lake turbidity. This effect occurred because a small group of generally scarce adults were characteristic of reference sites (Chalcolestes viridis, Lestes virens, Cordulia aenae, Leucorrhinia albifrons, and Sympetrum sanguineum). Exuviae of these same species were less abundant at restored sites, but exuvial assemblages overall did not discriminate between restored and reference lakes. We conclude that lake restoration by liming can reduce diversity and larval numbers among odonates and subtly affects adult assemblages. In this case study, adult assemblages discriminated best between the lake types involved in the experiment, but important additional information arose from exuvial abundance and structure. This study indicates that natural recovery processes after acidification in formerly open‐cast areas––rather than chemical intervention through liming––might lead to preferable conservation outcomes.
Effects of Restoration on Plant Species Richness and Composition in Scandinavian Semi‐Natural Grasslands
Authors: Lindborg Regina , Eriksson Ove
Published: August 2004

Plant species richness in rural landscapes of northern Europe has been positively influenced by traditional management for millennia. Owing to abandonment of these practices, the number of species‐rich semi‐natural grasslands has decreased, and remaining habitats suffer from deterioration, fragmentation, and plant species decline. To prevent further extinctions, restoration efforts have increased during the last decades, by reintroducing grazing in former semi‐natural grasslands. To assess the ecological factors that might influence the outcome of such restorations, we made a survey of semi‐natural grasslands in Sweden that have been restored during the last decade. We investigated how plant species richness, species density, species composition, and abundance of 10 species that are indicators of grazing are affected by (1) the size of the restored site, (2) the time between abandonment of grazing and restoration, (3) the time elapsed since restoration, and (4) the abundance of trees and shrubs at the restored site. Only two factors, abundance of trees and shrubs and time since restoration, were positively associated with total species richness and species density per meter square at restored sites. Variation in species composition among restored sites was not related to any of the investigated factors. Species composition was relatively similar among sites, except in mesic/wet grasslands. The investigated factors had small effects on the abundance of the grazing‐indicator species. Only Campanula rotundifolia responded to restoration with increasing abundance and may thus be a suitable indicator of improved habitat quality. In conclusion, positive effects on species richness may appear relatively soon after restoration, but rare, short‐lived species are still absent. Therefore, remnant populations in surrounding areas may be important in fully recreating former species richness and composition.
Use of anti‐secretory medication: a population‐based cohort study
Authors: Lassen A. , Hallas J. , Schaffalitzky de Muckadell O. B.
Published: August 2004

Background : Total use of anti‐secretory medication (H2 blockers and proton pump inhibitors) is increasing rapidly, but knowledge of factors related to the increasing use is sparse.

Aim : To describe development in the use of anti‐secretory medication between 1993 and 2002 at a population level.

Methods : We extracted data on use of anti‐secretory medication (H2‐blockers and proton pump inhibitors) and ulcerogenic drugs, demographic data, and data on gastroscopy and endoscopically verified oesophagitis and peptic ulcer diagnoses, from three large population‐based databases covering the County of Funen, Denmark 1990–2002 (population 470 000).

Results : Between 1993 and 2002 incidence of first time users was stable at 16.7/1000 persons/year. Total amount of consumed anti‐secretory medication increased from 10.5 DDD/1000 persons/day to 25.2 DDD/1000 persons/day. Ninety per cent of the increase was related to long‐term use of anti‐secretory medication (≥180 DDD/patient/year). In 1993 21% of the anti‐secretory medication was used by patients with oesophagitis, this increased to 28% in 2002. The proportion of medication used by peptic ulcer patients decreased from 29% in 1993 to 19% in 2002.

Conclusions : Total use of anti‐secretory medication increased as a result of more extensive long‐term use, and most of the medication was used by patients without diagnosed peptic ulcer or oesophagitis.
Basic fibroblast growth factor as a response parameter to infliximab in fistulizing Crohn's disease
Authors: Gao Q. , van Hogezand R. A. , Lamers C. B. H. W. , Verspaget H. W.
Published: August 2004

Background : Fibroblast growth factors play an important role in (patho)physiological processes such as wound healing and tissue repair. We previously showed that basic fibroblast growth factor is actively involved in inflammatory bowel disease processes. In the present retrospective study, we assessed whether serum basic fibroblast growth factor levels in Crohn's disease patients reflect the response to anti‐tumour necrosis factor‐α antibody infliximab treatment.

Aim and methods : Serum samples, biopsies and patient data from a subgroup of patients included in two placebo‐controlled trials were used. Fistulizing Crohn's disease patients (n = 42) were administered placebo or infliximab intravenously three times and evaluated for response up to 18 weeks. Biopsies from a subgroup of patients were stained for basic fibroblast growth factor using indirect immunohistochemistry. In the active Crohn's disease trial, patients (n = 24) received either placebo or infliximab once, and disease activity and serum basic fibroblast growth factor were assessed at weeks 0 and 4.

Results : Basic fibroblast growth factor levels at inclusion were comparable in the fistulizing Crohn's disease patients regardless of whether the fistulas did or did not respond or completely heal (median range: 9.3–10.6 pg/mL). At the end of follow‐up basic fibroblast growth factor levels were lower in patients who responded (9.2 pg/mL, P = 0.06) or who were completely healed (8.9 pg/mL, P = 0.009) when compared with patients did not respond/heal (14.5 pg/mL), the latter not significantly increased from baseline. Decreases in the perianal disease activity index and open fistula scores at the end of the follow‐up were significantly correlated with the decrease in basic fibroblast growth factor (R = 0.41; P = 0.012 and R = 0.35; P =0.027, respectively). Immunohistological evaluation also showed a trend towards decreased basic fibroblast growth factor expression in intestinal biopsies of these patients. Patients with active disease, i.e. a Crohn's disease activity index ≥220 combined from the two studies, were found to have significantly (P = 0.0046) lower baseline serum basic fibroblast growth factors levels than those with inactive disease (5.3 vs. 10.3pg/mL, respectively). Treatment of the active disease patients did not affect the serum basic fibroblast growth factor level, although a general decrease in disease activity was observed with infliximab treatment.

Conclusions : Healing of fistulizing/perianal Crohn's disease seems to be reflected by a decrease in high serum basic fibroblast growth factor. Basic fibroblast growth factor levels do not relate with response in active Crohn's disease patients.
JAM4 enhances hepatocyte growth factor‐mediated branching and scattering of Madin‐Darby canine kidney cells
Authors: Mori Hiroki , Hirabayashi Susumu , Shirasawa Madoka , Sugimura Haruhiko , Hata Yutaka
Published: August 2004

Junctional adhesion molecule (JAM) 4 is a member of immunoglobulin superfamily that interacts with MAGI‐1, a membrane‐associated guanylate kinase protein at tight junctions in epithelial cells. We prepared Madin‐Darby canine kidney II (MDCK) cells expressing JAM4 (MDCK‐JAM4) and compared them with wild MDCK cells. The treatment of hepatocyte growth factor (HGF) induced more prominent branching and scattering in MDCK‐JAM4 cells. Subsequently we attempted to identify signalling pathways modified by JAM4. The over‐expression of JAM4 induced the formation of protrusions in COS‐7 cells. Although those protrusions were different from typical lamellipodia, the dominant negative mutant of Rac suppressed them. The pull‐down assay using CDC42 and Rac interactive binding domain of PAK also supports that Rac is activated in COS‐7 cells expressing JAM4. Taken together, JAM4 itself activates Rac and may augment Rac activation by HGF, resulting in the enhancement of branching and scattering.
Requirement of the actin cytoskeleton for the association of nectins with other cell adhesion molecules at adherens and tight junctions in MDCK cells
Authors: Yamada Akio , Irie Kenji , Fukuhara Atsunori , Ooshio Takako , Takai Yoshimi
Published: August 2004

Nectins, Ca2+‐independent immunoglobulin‐like cell adhesion molecules (CAMs), first form cell‐cell adhesion where cadherins are recruited, forming adherens junctions (AJs) in epithelial cells and fibroblasts. In addition, nectins recruit claudins, occludin, and junctional adhesion molecules (JAMs) to the apical side of AJs, forming tight junctions (TJs) in epithelial cells. Nectins are associated with these CAMs through peripheral membrane proteins (PMPs), many of which are actin filament‐binding proteins. We examined here the roles of the actin cytoskeleton in the association of nectins with other CAMs in MDCK cells stably expressing exogenous nectin‐1. The nectin‐1‐based cell‐cell adhesion was formed and maintained irrespective of the presence and absence of the actin filament‐disrupting agents, such as cytochalasin D and latrunculin A. In the presence of these agents, only afadin remained at the nectin‐1‐based cell‐cell adhesion sites, whereas E‐cadherin and other PMPs at AJs, α‐catenin, β‐catenin, vinculin, α‐actinin, ADIP, and LMO7, were not concentrated there. The CAMs at TJs, claudin‐1, occludin and JAM‐1, or the PMPs at TJs, ZO‐1 and MAGI‐1, were not concentrated there, either. These results indicate that the actin cytoskeleton is required for the association of the nectin‐afadin unit with other CAMs and PMPs at AJs and TJs.
Expression, Lipoylation and Structure Determination of Recombinant Pea H‐Protein in Escherichia coli
Authors: Macherel David , Bourguignon Jacques , Forest Eric , Faure Magali , Cohen‐Addad Claudine , Douce Roland
Published: August 2004

A synthetic gene encoding the entire mature H protein of the glycine decarboxylase complex from pea (Pisum sativum L.) was constructed and expressed in Escherichia coli. The recombinant H protein, which after the induction period constituted more than half of the E. coli protein, was found in a soluble form. Activity measurements and mass‐spectrometry analysis of the purified protein showed that, in the absence or presence of 5[3‐(1,2)‐dithiolanyl]pentanoic acid (lipoic acid) in the culture medium, recombinant H protein could be produced as the unlipoylated apoform or as the lipoylated form, respectively. Addition of chloramphenicol to the culture medium after induction increased the proportion of lipoylated H protein. High rates of lipoylation of the H apoprotein were measured in vivo and in vitro, revealing that the recombinant pea H protein was an excellent substrate for the E. coli lipoyl‐ligase. The three‐dimensional structure of the recombinant H apoprotein was determined at a 0.25‐nm resolution. It was almost identical to the structure of the native pea leaf enzyme, which indicates that the recombinant protein folds properly in E. coli and that the lipoyl‐ligase recognizes a three‐dimensional structure in order to add lipoic acid to its specific lysine residue. It is postulated that the high level of expression and lipoylation of recombinant H protein may be due to the protein retaining the structure of the original enzyme.
Insulin and Phorbol Ester Stimulate Initiation Factor eIF–4E Phosphorylation by Distinct Pathways in Chinese Hamster Ovary Cells Overexpressing the Insulin Receptor
Authors: Flynn Andrea , Proud Christopher G.
Published: August 2004

We have developed a one‐dimensional isoelectric focusing technique to measure changes in the steady‐state phosphorylation of the cap‐binding initiation factor, eIF‐4E. We have used a Chinese hamster ovary cell line transfected with the human insulin receptor (CHO.T cells) to study the regulation of eIF‐4E phosphorylation by insulin and other stimuli. Exposure of CHO.T cells to insulin, phorbol ester or serum resulted in a rapid increase (up to twofold) in eIF‐4E phosphorylation. As a control, we have also performed experiments with the parental cell line, CHO.K1 cells, in which both serum and phorbol ester, but not nanomolar concentrations of insulin, produce similar changes in eIF‐4E phosphorylation.

We have used two complementary approaches to study the role of protein kinase C (PKC) in these responses: a highly specific inhibitor of PKC and down‐regulation of PKC by prior treatment of the cells with phorbol ester. In CHO.T cells, both approaches indicate that PKC is required for the response to phorbol ester but that insulin and serum each increase elF‐4E phosphorylation by a mechanism(s) independent of this protein kinase. Similarly, PKC is necessary for the effects of phorbol ester, but not of serum, on eIF‐4E phosphorylation in CHO.K1 cells. These data indicate that multiple signal transduction mechanisms are involved in the modulation of eIF‐4E phosphorylation and the implications of these findings are discussed.
Functional Analysis of Human/Chicken Transferrin Receptor Chimeras Indicates that the Carboxy‐Terminal Region is Important for Ligand Binding
Authors: Buchegger Franz , Trowbridge Ian S. , Liu Li‐Fung Sue , White Suhaila , Collawn James F.
Published: August 2004

Chimeric human/chicken transferrin receptors have been constructed using the polymerase chain reaction. Different regions of the 671‐residue external domain of the human transferrin receptor were replaced by the corresponding sequences from the chicken transferrin receptor. As chicken transferrin receptors do not bind human transferrin, functional analysis of such chimeric receptors provides an approach to define the ligand‐binding site of the human transferrin receptor. Four of 16 chimeric human/chicken transferrin receptors expressed in chick embryo fibroblasts were efficiently transported to the plasma membrane and displayed on the cell surface. Studies of the four chimeric receptors indicated that binding of human transferrin was abolished if the carboxy terminal 192 amino acids of the human transferrin receptor (residues 569–760) were replaced with the corresponding region from the chicken transferrin receptor. Further, a chimeric receptor in which the carboxy‐terminal 72 residues were derived from the chicken transferrin receptor exhibited a 16‐fold decrease in binding affinity for human transferrin. In contrast, analysis of the other two chimeric receptors showed that 340 amino acids of the human transferrin receptor external domain more proximal to the transmembrane region (residues 151–490) could be replaced with the corresponding region from the chicken transferrin receptor without loss of high‐affinity ligand binding. In contrast, two mAbs against the human transferrin receptor external domain, B3/25 and D65.3, that do not compete with transferrin binding, do not bind the chimeric transferrin receptors in which the membrane proximal part is replaced by chicken sequences, while they do bind the two other chimeric transferrin receptors with high affinity. These data indicate that sequence differences in the carboxy‐terminal region of human and chicken transferrin receptor external domains are important for the species specificity of transferrin binding and imply that this portion of the human transferrin receptor is critical for ligand binding.
A New Mechanism in Serine Proteases Catalysis Exhibited by Dipeptidyl Peptidase IV (DP IV)
Authors: Brandt Wolfgang , Ludwig Olaf , Thondorf Iris , Barth Alfred
Published: August 2004

Herein we present results of semiempirical molecular orbital calculations employing the PM3 molecular model. The compounds studied are related to substrates of the serine protease dipeptidyl peptidase IV (DP IV). Our goal was the thermodynamic characterization of the DP IV‐enzyme‐catalyzed reaction pathway. A new mechanism of serine proteases catalysis is presented. We found that a tetrahedral intermediate can be stabilized by the formation of an oxazolidine ring with the nonscissile P2‐P1 peptide bond. In this way, the negative charge of the tetrahedral intermediate around the scissile bond is transferred to the carbonyl oxygen atom of the preceding peptide bond. This negative charge can be compensated by a proton transfer from the positively charged N‐terminus to this oxygen atom. It is shown that the positively charged N‐terminus is the driving force in this particular serine protease mechanism of catalysis. The mechanism is supported by observed secondary hydrogen isotope effects on the Cα proton for an alanine residue in the P2 position. We suggest a trans‐cis isomerisation around the P2‐P1 peptide bond in the final step of the acylation and cleavage of the substrates. The results obtained by our theoretical calculations are compared with several experimental findings supporting the suggested mechanism.
Isolation and Characterisation of Dhel II, a DNA Helicase from Drosophila Melanogaster Embryos Stimulated by Escherichia Coli‐type Single‐Stranded‐DNA‐Binding Proteins
Authors: Thömmes Pia , Marton Richard F. , Cotterill Sue
Published: August 2004

We have purified a DNA helicase from Drosophila embryos by following unwinding activity during the purification of the cellular single‐stranded DNA‐binding protein dRP‐A. This DNA helicase unwinds DNA 5′ to 3′, has a salt‐tolerant activity, and has a preference for purine triphosphates as cofactors for the unwinding reaction. The purified enzyme consists of a single polypeptide of 120 kDa, which cosediments with the helicase activity. Sedimentation analysis suggests that this polypeptide exists as a monomer under high and low salt conditions. Dhel II is able to unwind long stretches of DNA, but with decreased efficiency. Addition of Escherichia coli‐like single‐stranded DNA‐binding proteins stimulates the unwinding activity at least 10‐fold on substrates greater than 200 nucleotides. In particular, the mitochondrial single‐stranded DNA‐binding protein isolated from Drosophila embryos is able to stimulate unwinding by dhel II. These properties show that the helicase described is different from another Drosophila helicase dhel I; it has thus has been classified as dhel II.
The Expression of Mitochondrial 3‐Hydroxy‐3‐Methylglutaryl‐Coenzyme‐A Synthase in Neonatal Rat Intestine and Liver is Under Transcriptional Control
Authors: Serra Dolors , Bellido David , Asins Guillermina , Arias Gladys , Vilaró Senén , Hegardt Fausto G.
Published: August 2004

Mitochondrial 3‐hydroxy‐3‐methylglutaryl‐CoA (HOMeGlt‐CoA) synthase regulates ketogenesis in the liver of adult rat and in the intestine and liver of neonatal animals but whose mechanisms of regulation have not been fully defined. To investigate transcriptional control of this gene in intestine and liver of suckling rats a quantitative PCR amplification of the pre‐mRNA (heteronuclear RNA), composed of part of the first exon and of the first intron, was carried out. Results show that the intestinal pre‐mRNA for mitochondrial HOMeGlt‐CoA synthase from suckling rats follows a pattern that is nearly identical to that of mature mRNA, with maximum levels on the ninth postnatal day then decreasing smoothly so that at weaning there is no transcriptional activity. Mitochondrial HOMeGlt‐CoA synthase protein follows a pattern that is identical to the pre‐mRNA and mature mRNA, suggesting no translational regulation. The changes in transcriptional activity are not produced by the presence of an alternative promoter, since the transcription‐initiation site is identical in several tissues assayed, including intestine and liver. Enterocytes are the only intestinal cells that express this ketogenic enzyme, as deduced from immunolocalization experiments. The mature intestinal protein is located in mitochondria and not in the cytosol, which coincides with what is found in liver. By using analogous techniques we conclude that hepatic pre‐mRNA of mitochondrial HOMeGlt‐CoA synthase from suckling rats follows a pattern of expression identical to that of mature hepatic mRNA, which also suggests a transcriptional modulation of this gene in the liver of neonatal rats.
Antigenic Regions of Human Chromogranin A and their Topographic Relationships with Structural/Functional Domains
Authors: Corti Angelo , Longhi Renato , Gasparri Anna , Chen Fuxiang , Pelagi Micaela , Siccardi Antonio G.
Published: August 2004

Chromogranin A is a protein contained in the secretory granules of many neuroendocrine cells. The linear antigenic sites of human chromogranin A were studied by examining the cross‐reaction of polyclonal and monoclonal anti‐chromogranin A antibodies with native chromogranin A and with synthetic peptides encompassing most of the chromogranin A sequence. Chromogranin A residues 1–20, 47–67, 107–158, 254–297, 331–375, and 395–419 were found to be poorly or not antigenic, while residues 25–46, 163–210, 231–253, 298–314 and 68–106, 222–230, 315–330, 376–394 were found to contain weak and strong antigenic sites, respectively. Residues 68–70 (GAK) and 81–90 (GFEDELSEVL) were strongly recognized by two mouse mAbs (B4E11 and A11, respectively). Since mAb A11 has been previously used for immunohistochemical analysis of chromogranin‐A‐producing tissues from different species and for in vivo imaging of chromogranin‐A‐positive endocrine tumors, these results imply that at least part of the 81–90 region is surface‐exposed in cryostat tissue sections as well as in vivo. The results may help in selecting new antibodies with improved affinity and immunogenicity for in vivo targeting of chromogranin‐A‐producing tumors.