bluuebunny/crossref_metadata_2025 huggingface dataset:
Governance and Strategic Leadership in Entrepreneurial Firms
Authors: Daily Catherine M. , McDougall Patricia P. , Covin Jeffrey G. , Dalton Dan R.
Published: December 2005

Corporate governance has been a central focus of strategic management research, particularly the associations among governance structures, strategic leaders, and firm performance. Extant research, however, provides little evidence of systematic relationships in these areas. There are a series of theoretical/conceptual rationales suggesting that such relationships might be more pronounced in entrepreneurial firms. Accordingly, we provide an overview and synthesis of the entrepreneurship literature addressing the intersection of governance and strategic leadership with firm performance. The strongest relationships reflected in this literature are consistent with a resource dependence perspective of the firm. We conclude with several suggestions for advancing research in this important domain.
Alliance Management as a Source of Competitive Advantage
Authors: Ireland R. Duane , Hitt Michael A. , Vaidyanath Deepa
Published: December 2005

Strategic alliances are an important source of resources, learning, and thereby competitive advantage. Few firms have all of the resources needed to compete effectively in the current dynamic landscape. Thus, firms seek access to the necessary resources through alliances. We examine the management of strategic alliances using the theoretical frames of transactions cost, social network theory and the resource-based view. Alliances must be effectively managed for their benefits to be realized. Effective alliance management begins with selecting the right partner. Furthermore, alliances must be managed to build social capital and knowledge. To maximize cooperation among the partners, a trust-based relationship must be developed. Therefore, we conclude that managing alliances is crucial for firms to gain competitive advantage and create value with strategic alliances.
Explaining Injustice: The Interactive Effect of Explanation and Outcome on Fairness Perceptions and Task Motivation
Authors: Colquitt Jason A. , Chertkoff Jerome M.
Published: December 2005

This study examined the effects of providing an explanation on procedural fairness, distributive fairness, and task motivation under both favorable and unfavorable outcome conditions. Participants (N = 164) arrayed in three-person groups made a selection decision concerning which of two candidates would be better at a brainstorming task, with the understanding that the chosen candidate would be added to their group. The experimenter could choose to uphold or overrule the group’s decision, creating the manipulation of outcome favorability. Our results showed that the outcome favorability manipulation, and participants’ self-reported outcome expectations, moderated the effects of providing an explanation, such that an explanation had the most positive effects in light of unexpected, unfavorable outcomes.
The Influence of Gender on the Performance of Organizational Citizenship Behaviors
Authors: Kidder Deborah L.
Published: December 2005

This paper examines the relationship between gender and reports of organizational citizenship behaviors (OCBs). Drawing on gender role theory, I examine the effects of employee gender (male/female), gender orientation (masculine/feminine) and gender-dominated occupational choice (nurse/engineer) on OCBs. I hypothesize relationships between gender and the performance of gender-congruent OCBs, i.e., female-typed altruism and male-typed civic virtue. The results demonstrate significant differences in line with traditional gender roles. Implications are discussed.
Building Trust in Cross-Cultural Collaborations: Toward a Contingency Perspective
Authors: Luo Yadong
Published: December 2005

This study examines the trust-performance link in international strategic alliances (ISAs) from a contingency view. Departing from previous research, we argue that the trust-performance link varies according to its underlying contingency variables such as alliance age, risk commensuration, market uncertainty, resource interdependency, and reciprocal commitment. Our analysis of 255 ISAs in a dynamic environment (the People’s Republic of China) suggests that trust plays a stronger role in improving ISA performance such as sales and profitability when an alliance is younger, risk is more commensurate between parties, market is less volatile, interpartner dependency in resources is greater, and commitment to the ongoing partnership from each party is higher. Cultural distance between alliance parties does not moderate the trust-performance link but influences the level of trust.
Choice Situation, Refocusing, and Post-Bankruptcy Performance
Authors: Dawley David D. , Hoffman James J. , Lamont Bruce T.
Published: December 2005

The current study sheds additional light on how and when firms improve their performance after having filed for Chapter 11 reorganization protection. Based on the work of Hrebiniak and Joyce [Administrative Science Quarterly 30 (1985) 336] and Marlin, Lamont and Hoffman [Strategic Management Journal 15 (1994) 229], a framework is developed that identifies which distressed firms have the best chances of surviving bankruptcy and the extent to which refocusing, a popularly prescribed remedy for these ailing firms, will aid their plight. The results demonstrate the utility of viewing bankruptcy reorganizations as different choice situations, where firms have varying levels of strategic choice, determined largely by their stockpiles of redeployable resources, and face different degrees of environmental constraint. Only firms with relatively high strategic choice or low environmental constraint were found to benefit from refocusing actions. That is, the performance effects of at least one popular remedy, refocusing-type business portfolio initiatives, appear contingent on the choice situation confronting firms under Chapter 11 protection.
Structured Conflict and Consensus Outcomes in Group Decision Making
Authors: Priem Richard L. , Harrison David A. , Muir Nan Kanoff
Published: December 2005

Pressures for early consensus during group decision processes often lead to poor choices. However, consensus as an outcome of group decision processes is often desirable for implementing choices. We propose and test hypotheses that structured decision making techniques designed to enhance the expression of cognitive conflict will, paradoxically, (1) strengthen group consensus about and individual acceptance of the group S eventual choices, and (2) increase member satisfaction with the group. Faced with a realistic managerial scenario, nineteen groups in this study deliberated using the structured, conflict-enhancing dialectical inquiry (DI) approach; nineteen used the consensus (C) approach. Group consensus on the decision, individual acceptance of the decision, and member satisfaction with the group were higher in the DI than in the C conditions. We discuss implications for group decision aids and for future laboratory and field studies of group consensus on a course of action.
Why Meta-Analysis Doesn’t Tell Us What the Data Really Mean: Distinguishing between Moderator Effects and Moderator Processes
Authors: Russell Craig J. , Gilliland Stephen W.
Published: December 2005

Traditional approaches to detecting the presence of moderators in meta-analyses involve inferences drawn from the residual variance in criterion-related validities (a) after correcting for sampling error and statistical artifacts. James, Demaree, Mulaik, and Ladd (1992) argued that these residualized interpretations of meta-analytic results may be spurious when statistical artifacts covary with true moderators. We extend their model to suggest that situational moderators might also covary with sample size and content (i.e., nonrandom sample selection error), causing meta-analysis to be uninterpretable and a significant correlation between criterion-related validities and ni. We investigate this possibility on studies examining criterion-related validities ofpeer nominations originally reported by Kane and Lawler (1978). Application of residualized meta-analysis suggests the presence of moderator effects, but a significant correlation between ri and ni precludes interpretation of the moderator process behind these effects. More generally, we argue that the nature of true contingencies cannot be inferred from meta-analytic summaries of traditional criterion-related validity studies. Primary research with appropriate controls is the only means of identifying true moderator effects and processes on criterion-related validity.
The Affective Implications of Perceived Congruence with Culture Dimensions during Organizational Transformation
Authors: Harris Stanley G. , Mossholder Kevin W.
Published: December 2005

The influence of individuals’ congruence with an organization’s culture on their affective orientations toward the organization has been the focus of a growing body of research. The present study contributes to this research by examining this relationship (I) in the context of an organization undergoing significant cultural transformation, and (2) across four theoretically identified dimensions of culture. We found that, across all four culture dimensions, the discrepancy between individuals’ assessments of the current culture and their ideal culture explained significant variance in two organization-focused affective outcomes, organizational commitment and optimism about the organization’s future. In contrast, the congruence effects across the four culture dimensions were not uniformly significant for job satisfaction, job involvement, and job turnover intention. The implications of these findings for future individual-culture congruence theory and research are considered.
Dynamic Core Competences through Meta-Learning and Strategic Context
Authors: Lei David , Hitt Michael A. , Bettis Richard
Published: December 2005

Traditional approaches to studying competitive advantage, while valuable, are not adequate to explain how firms can operate effectively in turbulent and often chaotic environments. A resource or skill-based view focusing on development and application of core competences is offered to supplement the traditional approaches. We present a model of the development and outcomes of dynamic core competences based on organizational meta-learning. A firm’s core competence(s) is defined as a set of problem-defining and problem-solving insights that fosters the development of idiosyncratic strategic growth alternatives. Dynamic core competences are based on the integration into systemic meta-learning of universal and tacit knowledge through information transfer, redefinition of heuristics and continuous improvement based on experimentation and the development of firm-specific skills based on dynamic routines. Dynamic core competences can be leveraged to create growth alternatives of global diversification, new applications of existing technologies and/or the development of new lines of business. Finally, dynamic core competences can be used to reduce uncertainty and to induce path dependencies that create causal ambiguity (making imitation from other firms difficult). In so doing, they can form the basis of competitive advantages.
Configurations of Manufacturing Strategy, Business Strategy, Environment and Structure
Authors: Ward Peter T. , Bickford Deborah J. , Leong G. Keong
Published: December 2005

By developing strategic configurations which describe commonly used paths to competitive advantage for manufacturers, this paper reconciles some basic concepts from competitive strategy and manufacturing strategy. Four basic strategic configurations are identified: niche differentiator, broad differentiator, cost leader, and lean competitor. The configurations are traced conceptually through competitive strategy, organizational structure, environment, and a strategic framework of manufacturing capabilities and decisions. Examples from the major home appliance industry are provided for each configuration.
Assessing the Non-Random Sampling Effects of Subject Attrition in Longitudinal Research
Authors: Goodman Jodi S. , Blum Terry C.
Published: December 2005

The potential effects of attrition in longitudinal research are addressed and a procedure for assessing its effects is recommended. We recommend that researchers assess the effects of subject attrition on their data by assessing: (1) the presence of non-random sampling using multiple logistic regression, (2) mean differences on the study’s variables between those who responded and did not respond to the subsequent data collection, (3) the restriction or enhancement of variances, and (4) changes in relationships among variables due to attrition. We demonstrate the procedure using data collected from a random sample of employed adults in the US regarding job satisfaction, job characteristics, demographics, and mood. In our data, subject attrition led to non-random sampling, affected the means and variances of some of the variables, but did not affect the relationships among the variables. The effects of subject attrition may be sample specific, but the procedure recommended for assessing its effects may be used in other data sets and substantive areas.
Latent Variable Models in the Investigation of Salary Discrimination: Theory and Practice
Authors: Millsap Roger E. , Taylor Ross
Published: December 2005

Statistical methods play an important role in salary discrimination litigation. Regression analysis is the most widely used method in this application. In regression analysis, group differences in salary are evaluated among employees who have been matched on measured “merit” variables (e.g., years of job experience). Difficulties often arise because important merit variables may be unmeasured, or because the available measures of merit are fallible. An alternative approach in this case lies in the use of several latent variable path models that have been proposed for the salary problem (Birnbaum, 1979; McFatter, 1987). The theoretical and practical implications of these models are discussed. The use of the models is illustrated in real data.
Governance Antecedents of Board Entrenchment: The Case of Classified Board Provisions
Authors: Sundaramurthy Chamu , Rechner Paula , Wang Weiren
Published: December 2005

Using a sample of 192 Standard & Poor’s 500 firms, we examine the impact of corporate governance and ownership context on a particular instance of board entrenchment: adoption of classified board provisions. Interestingly, while increased outsider representation measured simply as a proportion of outsiders does not affect the rate of adoption, reliance on a more fine grained measure, which includes other affiliations of outsiders, results in a marginally significant influence. Moreover, it appears that reliance on a simple proportional measure is likely to distort the effects of other variables. Finally, institutional stock ownership is found to be the most significant factor associated with decreased rate of adoption.
A Theory of Equitable Performance Standards
Authors: Kane Jeffrey S. , Freeman Kimberly A.
Published: December 2005

Performance standards are reconceptualized as the interface between measurement and evaluation. A job’s performance standards are theorized to be equitable to the extent that they require levels of effectiveness equal to those collectively viewed as justified by the standing of the job’s pay rate relative to the labor market median. Methodology for creating equitable performance standards is presented, and the implications of implementing such performance standards are discussed in reference to compensation strategy and practice and to the potential financial benefits to organizations.
Merger Strategies and Shareholder Value During Times of Relaxed Antitrust Enforcement: The Case of Large Mergers During the 1980s
Authors: Lubatkin Michael , Srinivasan Narasimhan , Merchant Hemant
Published: December 2005

Most of what we know about the merger strategy-shareholder value relationship comes from studies based on the 1948-1979 FTC Large Merger Series. However, the market for acquisitions changed dramatically in the 1980s as government policies facilitated “mergers for efficiency, ” rather than “merger for diversity. ” We update the list of large mergers through 1988, classify each with a categorical and continuous measure of merger “relatedness, ” and then calculate three capital market measures of value creation. Regardless of construct de& nition, we find no evidence that the mergers in the 1980s were more strategic or value creators than those from prior periods.
Further Validation of the Perceptions of Politics Scale (Pops): A Multiple Sample Investigation
Authors: Kacmar K. Michele , Carlson Dawn S.
Published: December 2005

Although political behavior in organizations is ubiquitous, measuring it is often difficult. In one attempt to create such a measure, Kacmar and Ferris (1991) developed and evaluated the psychometric properties of the Perceptions of Politics Scale (POPS). Later, Nye and Witt (1993) examined the dimensionality of POPS and its construct validity by comparing it with the Survey of Perceived Organizational Support (SPOS; Eisenberger, Huntington, Hutchison & Sowa, 1986). The present research extends these previous studies by using structural equation modeling to evaluate the dimensional, reliability, and validity of POPS across three different studies utilizing nine different samples for a total of 2758 respondents. Results suggested that some of the original POPS items were ineffective and needed to be removed or replaced. Hence, some of the original items were deleted and additional items were generated and tested to produce a refined and revised version of POPS.
A Dimensional Analysis of the Relationship between Psychological Empowerment and Effectiveness Satisfaction, and Strain
Authors: Spreitzer Gretchen M. , Kizilos Mark A. , Nason Stephen W.
Published: December 2005

This paper examines the contribution of each of the four dimensions in Thomas and Velthouse’s (1990) multidimensional conceptualization of psychological empowerment in predicting three expected outcomes of empowerment: effectiveness, work satisfaction, and job-related strain. The literature on the four dimensions of empowerment (i.e., meaning, competence, self-determination, and impact) is reviewed and theoretical logic is developed linking the dimensions to specific outcomes. The expected relationships are tested on a sample of managers from diverse units of a manufacturing organization and then replicated on an independent sample of lower-level employees in a service organization using alternative measures of the outcome variables. The results, largely consistent across the two samples, suggest that different dimensions are related to different outcomes and that no single dimension predicts all three outcomes. These results indicate that employees need to experience each of the empowerment dimensions in order to achieve all of the hoped for outcomes of empowerment.
How Effective are Harm Reduction Programmes for Drug Users? Some Insights from an Evaluation of the Programme at Sharan in Delhi
Authors: Priya Kumar Ravi , Singh Siddharth , Dorabjee Jimmy , Varma Suneet , Samson Luke
Published: December 2005

Drug use and the physical, psychological and social problems associated with it have been one of the major concerns among professionals in the domain of health and health psychology. One important reason for drug use being a matter of deep concern is the risk of HIV infection associated with it. Apart from the practice of unsafe sex among drug users, in recent decades sharing of needles/syringes by injecting drug users has contributed substantially to the spread of HIV/AIDS. The WHO has noted that the harm reduction approach provides an anxiety-free atmosphere (denied by the traditional abstinence-based intervention programmes) for drug users where they learn and discuss the personal social significance of not sharing needles/syringes and exchanging free needles/syringes. Importantly, apart from needle/syringe exchange, oral substitution of drugs, medical care and education to prevent HIV/AIDS, a harm reduction programme provides a psychological space to drug users that not only acts an emotional support but also enables them to reflect upon their life and risk behaviour. Apart from indicating the need of harm reduction programmes, this article also evaluates the effectiveness of such a programme run by Sharan, an NGO in Delhi, during 1999–2002. Apart from various components of the programme, unconditional acceptance of the drug users by the service providers has brought about substantial reduction in risk behaviour and noticeable improvement in their quality of life.
Five-star Doctors for the 21st Century
Authors: Jha Nilambar , Premarajan K.C. , Nagesh S. , Khanal S. , Thapa L.B.
Published: December 2005

The term ‘five-star doctor’ has been promoted to denote the model physician for today's society, who should be able to respond to the needs of both individual patients and their community. The B.P. Koirala Institute of Health Sciences (BPKIHS) has adopted integrated, partially problem-based, organ system and community-oriented curriculum for medical graduates. The various field programmes related to community diagnosis, health care delivery system, family health exercise, epidemiology for health management, managerial skills for health services, and learning in fields are incorporated in the MBBS curriculum. Five-month postings during internships in zonal and district hospitals and one month in district public health offices and primary health centres are unique programmes to make it more socially accountable. Such exposure for MBBS students makes them to attain five-star status, that is, caregiver, decision maker, communicator, community leader and manager. Thus, BPKIHS is working as a pioneer in an endeavour to create five-star doctors for the 21st century.
Role of CXCR3 carboxyl terminus and third intracellular loop in receptor-mediated migration, adhesion and internalization in response to CXCL11
Authors: Dagan-Berger Michal , Feniger-Barish Rotem , Avniel Shani , Wald Hanna , Galun Eithan , Grabovsky Valentin , Alon Ronen , Nagler Arnon , Ben-Baruch Adit , Peled Amnon
Published: December 2005

The chemokine receptor CXCR3 is predominantly expressed on activated T and natural killer (NK) cells. CXCR3 and its ligands, CXCL11, CXCL10, and CXCL9, play a major role in T-helper 1 (Th1)–dependent inflammatory responses. CXCL11 is the most dominant physiological inducer of adhesion, migration, and internalization of CXCR3. To study the role of CXCR3 carboxyl-terminus and the third intracellular (3i) loop in chemokine-mediated migration, adhesion, and CXCR3 internalization, we generated CXCR3 receptors mutated in their distal (Ser-Thr domain) or proximal (trileucine domain) membrane carboxyl terminus, and/or the third intracellular loop. We found that migration of CXCR3-expressing HEK 293 cells toward CXCL11 was pertussis toxin–dependent and required the membrane proximal carboxyl terminus of CXCR3. Internalization induced by CXCL11 and protein kinase C (PKC) activation was also regulated by the membrane proximal carboxyl terminus; however, only CXCL11-induced internalization required the LLL motif of this region. Internalization and Ca2+ flux induced by CXCL11 were independent of the 3i loop S245, whereas migration at high CXCL11 concentrations, integrin-dependent adhesion, and actin polymerization were S245 dependent. Our findings indicate that CXCL11-dependent CXCR3 internalization and cell migration are regulated by the CXCR3 membrane proximal carboxyl terminus, whereas adhesion is regulated by the 3i loop S245. Thus, distinct conformational changes induced by a given CXCR3 ligand trigger different downstream effectors of adhesion, motility, and CXCR3 desensitization.
Apoptosis and complement-mediated lysis of myeloma cells by polyclonal rabbit antithymocyte globulin
Authors: Zand Martin S. , Vo Thuong , Pellegrin Tina , Felgar Raymond , Liesveld Jane L. , Ifthikharuddin Jainulabdeen J. , Abboud Camille N. , Sanz Ignacio , Huggins Jennifer
Published: December 2005

Current monoclonal antibody therapies for multiple myeloma have had limited success, perhaps due to narrow target specificity. We have previously described the ability of polyclonal rabbit antithymocyte globulin (rATG) to induce caspase- and cathepsin-mediated apoptosis in human B and plasma cells. We now extend this observation to myeloma cells. Complement independent cell death was measured after addition of rATG (1-1000 μg/mL) to cultures of myeloma cell lines or primary CD138+ isolates from patient bone marrow aspirates. rATG induced significant levels of apoptosis in myeloma cells as assayed by caspase induction, annexin V binding, subdiploid DNA fragmentation, plasma-membrane permeability, and loss of mitochondrial-membrane potential. Addition of complement greatly augmented myeloma-cell death. Binding of rATG to individual myeloma cell-surface proteins, primarily CD38, CD52, CD126, and CD138, was demonstrated by competitive inhibition experiments with targeted monoclonal antibodies. Three pathways of cell death were identified involving caspase activation, cathepsin D, and the genistein sensitive tyrosine kinase pathway. F(ab′)2 fragments of rATG had reduced proapoptotic activity, which was restored by coincubation with Fc fragments, and anti-CD32 or anti-CD64 antibodies. We conclude that rATG is an effective agent for in vitro induction of apoptosis in multiple myeloma, and that exploratory clinical trials may be warranted.
U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7
Authors: Savarese Emina , Chae Ohk-wha , Trowitzsch Simon , Weber Gert , Kastner Berthold , Akira Shizuo , Wagner Hermann , Schmid Roland M. , Bauer Stefan , Krug Anne
Published: December 2005

Plasmacytoid dendritic cells (PDCs), which produce IFN-α in response to autoimmune complexes containing nuclear antigens, are thought to be critically involved in the pathogenesis of systemic lupus erythematosus (SLE). One of the immunostimulatory components of SLE immune complexes (SLE-ICs) is self DNA, which is recognized through Tlr9 in PDCs and B cells. Small nuclear ribonucleoproteins (snRNPs) are another major component of SLE-ICs in 30% to 40% of patients. In this study, we show that murine PDCs are activated by purified U1snRNP/anti-Sm ICs to produce IFN-α and proinflammatory cytokines and to up-regulate costimulatory molecules. The induction of IFN-α and IL-6 by U1snRNPs in murine bone marrow–derived PDCs required the presence of intact U1RNA and was largely dependent on Tlr7 but independent of Tlr3. Intracellularly delivered isolated U1snRNA and oligoribonucleotides derived from the stem loop regions and the Sm-binding site of U1snRNA efficiently induced IFN-α and IL-6 in Flt3L-cultured DCs in a Tlr7-dependent manner. The U1snRNA component of U1snRNP immune complexes, found in patients with SLE, acts as an endogenous “self” ligand for Tlr7 and triggers IFN-α and IL-6 production in PDCs.
Cross talk among Notch3, pre-TCR, and Tal1 in T-cell development and leukemogenesis
Authors: Talora Claudio , Cialfi Samantha , Oliviero Christian , Palermo Rocco , Pascucci Monica , Frati Luigi , Vacca Alessandra , Gulino Alberto , Screpanti Isabella
Published: December 2005

Integrated pathways are believed to determine hematopoietic cell fate and/or neoplastic transformation. Notch signaling has been shown to regulate T-cell differentiation and leukemogenesis. However, specific target genes and molecular partners are not fully elucidated. We show that Notch3 activation sustains aberrant SCL/Tal1 overexpression and phosphorylation in mature thymocytes. Furthermore, we define the role of SCL/Tal1 as a component of an activator complex, including phosphorylated Tal1 and Sp1, that specifically enhances cyclin D1 expression and demonstrate that Tal1/Sp1 specifically co-occupy the D1 promoter in vivo, only in the presence of pre-T-cell receptor (TCR). We therefore conclude not only that cyclin D1 is a target of the Tal1/Sp1 complex, but also that Notch3-dependent activation of pre-TCR/ERK signaling regulates SCL/Tal1 function.
Identifying a common molecular mechanism for inhibition of MITF and STAT3 by PIAS3
Authors: Levy Carmit , Lee Yu-Nee , Nechushtan Hovav , Schueler-Furman Ora , Sonnenblick Amir , Hacohen Shelley , Razin Ehud
Published: December 2005

Protein inhibitor of activated STAT3 (PIAS3) functions in vivo as a key molecule in suppressing the transcriptional activity of both microphthalmia transcription factor (MITF) and signal transducer and activator of transcription 3 (STAT3), 2 transcription factors that play a major role in the regulation of growth and function in mast cells and melanocytes. Previously, we have demonstrated binding of PIAS3 to MITF leading to the inhibition of MITF transcriptional activity. Following cellular activation, PIAS3 is released from MITF and binds to STAT3. Now we have localized a common binding motif in PIAS3 for MITF and STAT3. This motif (PIAS82-132), which contains 50 amino acids, is sufficient for the inhibition of both MITF and STAT3. Three-dimensional protein modeling demonstrated that this motif contains 2 alpha helices. Disruption of one of the helices led to the loss of PIAS3 inhibitory activity. In addition to contributing to our understanding of the mechanisms of PIAS3 activity, these results could pave the way toward the formulation of an antioncogenic agent for the inhibition of both STAT3 and MITF.
Frequent genomic alterations in epithelium measured by microsatellite instability following allogeneic hematopoietic cell transplantation in humans
Authors: Faber Philipp , Fisch Paul , Waterhouse Miguel , Schmitt-Gräff Annette , Bertz Hartmut , Finke Jürgen , Spyridonidis Alexandros
Published: December 2005

Although typically found in cancers, frameshift mutations in microsatellites have also been detected in chronically inflamed tissues. Allogeneic hematopoietic cell transplantation (HCT) may potentially produce chronic tissue stress through graft-versus-host reactions. We examined non-neoplastic epithelial tissues (colon, buccal) obtained 1 to 5061 days after human allogeneic HCT for the presence of genomic alterations at 3 tetranucleotide and 3 mononucleotide microsatellite loci. Novel bands indicative of microsatellite instability (MSI) at tetranucleotide repeats were detected in laser-microdissected colonic crypts and in buccal smears of 75% and 42% of patients who received an allograft, respectively. In contrast, no MSI was found in similar tissues from control subjects and from patients after intensive chemotherapy or in buccal cells from patients after autologous HCT. The MSI found in colon, which was often affected by graft-versus-host disease, was not due to loss of expression or nitrosylation of DNA repair proteins. MSI in clinically intact oral mucosa was more frequently found at later time points after HCT. MSI was also found in 3 posttransplant squamous cell cancers examined. Our data show that genomic alterations in epithelium regularly occur after allogeneic HCT and may be implicated in the evolution of posttransplantation diseases, including secondary cancer.
Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains
Authors: Wilson Karen HS , McIndoe Richard A , Eckenrode Sarah , Morel Laurence , Agarwal Anupam , Croker Byron P , She Jin-Xiong
Published: December 2005

Background

Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD), which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA). To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10) that were made to develop proteinuria by BSA overload.

Methods

Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy.

Results

Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta). Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria.

Conclusion

By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes.
Prevalence of overweight in children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorders: a chart review
Authors: Curtin Carol , Bandini Linda G , Perrin Ellen C , Tybor David J , Must Aviva
Published: December 2005

Background

The condition of obesity has become a significant public health problem in the United States. In children and adolescents, the prevalence of overweight has tripled in the last 20 years, with approximately 16.0% of children ages 6–19, and 10.3% of 2–5 year olds being considered overweight. Considerable research is underway to understand obesity in the general pediatric population, however little research is available on the prevalence of obesity in children with developmental disorders. The purpose of our study was to determine the prevalence of overweight among a clinical population of children diagnosed with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD).

Methods

Retrospective chart review of 140 charts of children ages 3–18 years seen between 1992 and 2003 at a tertiary care clinic that specializes in the evaluation and treatment of children with developmental, behavioral, and cognitive disorders. Diagnostic, medical, and demographic information was extracted from the charts. Primary diagnoses of either ADHD or ASD were recorded, as was information on race/ethnicity, age, gender, height, and weight. Information was also collected on medications that the child was taking. Body mass index (BMI) was calculated from measures of height and weight recorded in the child's chart. The Center for Disease Control's BMI growth reference was used to determine an age- and gender-specific BMI z-score for the children.

Results

The prevalence of at-risk-for-overweight (BMI >85th%ile) and overweight (BMI > 95th%ile) was 29% and 17.3% respectively in children with ADHD. Although the prevalence appeared highest in the 2–5 year old group (42.9%ile), differences among age groups were not statistically significant. Prevalence did not differ between boys and girls or across age groups (all p > 0.05). For children with ASD, the overall prevalence of at-risk-for-overweight was 35.7% and prevalence of overweight was 19%.

Conclusion

When compared to an age-matched reference population (NHANES 1999–2002), our estimates indicate that children with ADHD and with ASD have a prevalence of overweight that is similar to children in the general population.
Open field trial of genetically modified parthenocarpic tomato: seedlessness and fruit quality
Authors: Rotino Giuseppe Leonardo , Acciarri Nazareno , Sabatini Emidio , Mennella Giuseppe , Lo Scalzo Roberto , Maestrelli Andrea , Molesini Barbara , Pandolfini Tiziana , Scalzo Jessica , Mezzetti Bruno , Spena Angelo
Published: December 2005

Background

Parthenocarpic tomato lines transgenic for theDefH9-RI-iaaMgene have been cultivated under open field conditions to address some aspects of the equivalence of genetically modified (GM) fruit in comparison to controls (non-GM).

Results

Under open field cultivation conditions, two tomato lines (UC 82) transgenic for theDefH9-RI-iaaMgene produced parthenocarpic fruits.DefH9-RI-iaaMfruits were either seedless or contained very few seeds. GM fruit quality, with the exception of a higher β-carotene level, did not show any difference, neither technological (colour, firmness, dry matter, °Brix, pH) nor chemical (titratable acidity, organic acids, lycopene, tomatine, total polyphenols and antioxidant capacity – TEAC), when compared to that of fruits from control line. Highly significant differences in quality traits exist between the tomato F1 commercial hybrid Allflesh and the three UC 82 genotypes tested, regardless of whether or not they are GM. Total yield per plant did not differ between GM and parental line UC 82. Fruit number was increased in GM lines, and GM fruit weight was decreased.

Conclusion

The use in the diet of fruits from a new line or variety introduces much greater changes than the consumption of GM fruits in comparison to its genetic background. Parthenocarpic fruits, produced under open field conditions, contained 10-fold less seeds than control fruits. Thus parthenocarpy caused byDefH9-RI-iaaMgene represents also a tool for mitigating GM seeds dispersal in the environment.
Effects among healthy subjects of the duration of regularly practicing a guided imagery program
Authors: Watanabe Eri , Fukuda Sanae , Shirakawa Taro
Published: December 2005

Background

We examined a large number of healthy adults in the general community who had individually participated in a guided imagery (GI) program daily and for various durations, to examine the psychophysiological effects of a GI program within a healthy group.

Methods

We studied 176 subjects who had participated in sessions that were part of a guided imagery program, and who had practiced GI at home for 20 minutes once daily in a quiet place after mastering GI in the group sessions. The average duration of GI practiced at home was 6.88 ± 14.06 months (n = 138, range: 0 to 72). The Multiple Mood Scale (MMS), Betts (1909) Shortened Questionnaire on Mental Imagery (QMI), and a visual analog scale (VAS) of imagery vividness, salivary cortisol (CS) levels, general stress and general health were used in the sessions.

Results

We examined the relationship between the duration of daily GI practiced at home and MMS, QMI, CS, general health, and general stress at baseline. The subjects who had practiced GI at home longer had lower negative mood scores at baseline and lower severity of stress, and higher positive mood at baseline (both at a session and at home), general health, and QMI scores at baseline. The MMS change during a session and the duration of daily GI practiced at home were not correlated. Repeated-measures analysis of covariance showed that the duration of daily GI practiced as the covariate was not associated with changes in the three CS levels.

Conclusion

Although regularly practicing a GI program daily for 20 min did not affect the CS level or mood during a GI session for several hours, it kept a good condition of the general mental, physical well-being and their overall stress of the practitioners as they had practiced it for long duration. We postulate that subjects who have the high ability of imaging vividness showed the better mood, health status and less stress than those subjects who have the low ability of it did. The ability of image vividness of the long-term regular practitioners of GI was higher than its short-term or inexperienced practitioners, which allowed practitioners to produce more comfortable imagery. Consequently, the longer the duration that they had practiced GI program once a day regularly, the lower scores of their stress were and the higher scores of their health were. We suggest that the regular daily practice of a GI program might be connected to less stress and better health.
Antimicrobial activities of Eugenol and Cinnamaldehyde against the human gastric pathogen Helicobacter pylori
Authors: Ali Shaik Mahaboob , Khan Aleem A , Ahmed Irshad , Musaddiq M , Ahmed Khaja S , Polasa H , Rao L Venkateswar , Habibullah Chittoor M , Sechi Leonardo A , Ahmed Niyaz
Published: December 2005

Background

Eradication of Helicobacter pylori is an important objective in overcoming gastric diseases. Many regimens are currently available but none of them could achieve 100% success in eradication. Eugenol and cinnamaldehyde that are commonly used in various food preparations are known to possess antimicrobial activity against a wide spectrum of bacteria.

Aim

The present study was performed to assess the in vitro effects of eugenol and cinnamaldehyde against indigenous and standard H. pylori strains, their minimum inhibitory concentrations (MICs) and time course lethal effects at various pH.

Methods

A total of 31 strains (29 indigenous and one standard strain of H. pylori ATCC 26695, one strain of E. coli NCIM 2089) were screened. Agar dilution method was used for the determination of drug sensitivity patterns of isolates to the commonly used antibiotics and broth dilution method for the test compounds.

Results

Eugenol and cinnamaldehyde inhibited the growth of all the 30 H. pylori strains tested, at a concentration of 2 μg/ml, in the 9th and 12th hours of incubation respectively. At acidic pH, increased activity was observed for both the compounds. Furthermore, the organism did not develop any resistance towards these compounds even after 10 passages grown at sub-inhibitory concentrations.

Conclusion

These results indicate that the two bioactive compounds we tested may prevent H. pylori growth in vitro, without acquiring any resistance.
C/EBPbeta-2 confers EGF-independent growth and disrupts the normal acinar architecture of human mammary epithelial cells
Authors: Bundy Linda , Wells Sam , Sealy Linda
Published: December 2005

Background

The transcription factor, C/EBPbeta, is a key regulator of growth and differentiation in the mammary gland. There are three different protein isoforms of C/EBPbeta. C/EBPbeta-1 and -2 are transactivators, and differ by only 23 N-terminal amino acids present in beta-1 only. C/EBPbeta-3 (LIP) lacks the transactivation domain and represses transcription. Elevated C/EBPbeta-2 expression causes MCF10A normal human mammary epithelial cells to become transformed, undergo an epithelial to mesenchymal transition (EMT), and acquire an invasive phenotype. C/EBPbeta is a downstream transcriptional target of Ras signaling pathways and is required for Ras transformation of some cell types. Ras signaling pathways are activated in mammary epithelial cells by the ErbB receptor tyrosine kinase family. Therefore, we considered whether elevated C/EBPbeta-2 expression would resemble ErbB RTK activation in MCF10A cells.

Results

We show that elevated C/EBPbeta-2 expression confers EGF-independent growth in MCF10A mammary epithelial cells. However, MCF10A cells expressing C/EBPbeta-3 are not EGF-independent, and high C/EBPbeta-3 or LIP expression is incompatible with growth. C/EBPbeta-2 overexpression disrupts the normal acinar architecture of MCF10A cells in basement membrane cultures and induces complex multiacinar structures with filled lumen, similar to the consequences of aberrant ErbB2 activation.

Conclusion

Given the ability of C/EBPbeta-2 to confer EGF-independent growth to mammary epithelial cells as well as its capability for disrupting normal epithelial architecture and causing EMT, it is worth considering whether inhibitors which target ErbB family signaling pathways could be less effective in mammary epithelial cells with elevated nuclear C/EBPbeta-2 expression.
Cortactin and phagocytosis in isolated Sertoli cells
Authors: Wolski Katja M , Haller Edward , Cameron Don F
Published: December 2005

Background

Cortactin, an actin binding protein, has been associated with Sertoli cell ectoplasmic specializationsin vivo, based on its immunolocalization around the heads of elongated spermatids, but not previously identified in isolated Sertoli cells. In anin vitromodel of Sertoli cell-spermatid binding, cortactin was identified around debris and dead germ cells. Based on this observation, we hypothesized that this actin binding protein may be associated with a non-junction-related physiological function, such as phagocytosis. The purpose of this study was to identify the presence and distribution of cortactin in isolated rat Sertoli cells active in phagocytic activity following the addition of 0.8 μm latex beads.

Results

Sertoli cell monocultures were incubated with or without follicle stimulating hormone (FSH; 0.1 μg/ml) in the presence or absence of cytochalasin D (2 μM), as an actin disrupter. Cortactin was identified by standard immunostaining with anti-cortactin, clone 4F11 (Upstate) after incubation times of 15 min, 2 hr, and 24 hr with or without beads. Cells exposed to no hormone and no beads appeared to have a ubiquitous distribution of cortactin throughout the cytoplasm. In the presence of cytochalasin D, cortactin immunostaining was punctate and distributed in a pattern similar to that reported for actin in cells exposed to cytochalasin D. Sertoli cells not exposed to FSH, but activated with beads, did not show cortactin immunostaining around the phagocytized beads at any of the time periods. FSH exposure did not alter the distribution of cortactin within Sertoli cells, even when phagocytic activity was upregulated by the presence of beads.

Conclusion

Results of this study suggest cortactin is not associated with peripheralized actin at junctional or phagocytic sites. Further studies are necessary to clarify the role of cortactin in Sertoli cells.
Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management
Authors: Fleisher David R , Gornowicz Blake , Adams Kathleen , Burch Richard , Feldman Edward J
Published: December 2005

Background

Cyclic Vomiting Syndrome (CVS) is a disorder characterized by recurrent, stereotypic episodes of incapacitating nausea, vomiting and other symptoms, separated by intervals of comparative wellness. This report describes the clinical features, co-morbidities and problems encountered in management of 41 adult patients who met the diagnostic criteria for CVS.

Methods

This is a retrospective study of adults with CVS seen between 1994 and 2003. Follow-up data were obtained by mailed questionnaires.

Results

Age of onset ranged from 2 to 49 years. The duration of CVS at the time of consultation ranged from less than 1 year to 49 years. CVS episodes were stereotypic in respect of their hours of onset, symptomatology and length. Ninety-three percent of patients had recognizable prodromes. Half of the patients experienced a constellation of symptoms consisting of CVS episodes, migraine diathesis, inter-episodic dyspeptic nausea and a history of panic attacks. Deterioration in the course of CVS is indicated by coalescence of episodes in time. The prognosis of CVS is favorable in the majority of patients.

Conclusion

CVS is a disabling disorder affecting adults as well as children. Because its occurrence in adults is little known, patients experience delayed or mis-diagnosis and ineffectual, sometimes inappropriately invasive management.