bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3
Authors: Chen WanJun , Jin Wenwen , Hardegen Neil , Lei Ke-jian , Li Li , Marinos Nancy , McGrady George , Wahl Sharon M.
Published: December 2003

CD4+CD25+ regulatory T cells (Treg) are instrumental in the maintenance of immunological tolerance. One critical question is whether Treg can only be generated in the thymus or can differentiate from peripheral CD4+CD25− naive T cells. In this paper, we present novel evidence that conversion of naive peripheral CD4+CD25− T cells into anergic/suppressor cells that are CD25+, CD45RB−/low and intracellular CTLA-4+ can be achieved through costimulation with T cell receptors (TCRs) and transforming growth factor β (TGF-β). Although transcription factor Foxp3 has been shown recently to be associated with the development of Treg, the physiological inducers for Foxp3 gene expression remain a mystery. TGF-β induced Foxp3 gene expression in TCR-challenged CD4+CD25− naive T cells, which mediated their transition toward a regulatory T cell phenotype with potent immunosuppressive potential. These converted anergic/suppressor cells are not only unresponsive to TCR stimulation and produce neither T helper cell 1 nor T helper cell 2 cytokines but they also express TGF-β and inhibit normal T cell proliferation in vitro. More importantly, in an ovalbumin peptide TCR transgenic adoptive transfer model, TGF-β–converted transgenic CD4+CD25+ suppressor cells proliferated in response to immunization and inhibited antigen-specific naive CD4+ T cell expansion in vivo. Finally, in a murine asthma model, coadministration of these TGF-β–induced suppressor T cells prevented house dust mite–induced allergic pathogenesis in lungs.
The Helicobacter pylori Vacuolating Toxin Inhibits T Cell Activation by Two Independent Mechanisms
Authors: Boncristiano Marianna , Paccani Silvia Rossi , Barone Silvia , Ulivieri Cristina , Patrussi Laura , Ilver Dag , Amedei Amedeo , D'Elios Mario Milco , Telford John L. , Baldari Cosima T.
Published: December 2003

Helicobacter pylori toxin, VacA, damages the gastric epithelium by erosion and loosening of tight junctions. Here we report that VacA also interferes with T cell activation by two different mechanisms. Formation of anion-specific channels by VacA prevents calcium influx from the extracellular milieu. The transcription factor NF-AT thus fails to translocate to the nucleus and activate key cytokine genes. A second, channel-independent mechanism involves activation of intracellular signaling through the mitogen-activated protein kinases MKK3/6 and p38 and the Rac-specific nucleotide exchange factor, Vav. As a consequence of aberrant Rac activation, disordered actin polymerization is stimulated. The resulting defects in T cell activation may help H. pylori to prevent an effective immune response leading to chronic colonization of its gastric niche.
Activation of Transforming Growth Factor β by Malaria Parasite-derived Metalloproteinases and a Thrombospondin-like Molecule
Authors: Omer Fakhreldin M. , de Souza J. Brian , Corran Patrick H. , Sultan Ali A. , Riley Eleanor M.
Published: December 2003

Much of the pathology of malaria is mediated by inflammatory cytokines (such as interleukin 12, interferon γ, and tumor necrosis factor α), which are part of the immune response that kills the parasite. The antiinflammatory cytokine transforming growth factor (TGF)-β plays a crucial role in preventing the severe pathology of malaria in mice and TGF-β production is associated with reduced risk of clinical malaria in humans. Here we show that serum-free preparations of Plasmodium falciparum, Plasmodium yoelii 17XL, and Plasmodium berghei schizont-infected erythrocytes, but not equivalent preparations of uninfected erythrocytes, are directly able to activate latent TGF-β (LatTGF-β) in vitro. Antibodies to thrombospondin (TSP) and to a P. falciparum TSP-related adhesive protein (PfTRAP), and synthetic peptides from PfTRAP and P. berghei TRAP that represent homologues of TGF-β binding motifs of TSP, all inhibit malaria-mediated TGF-β activation. Importantly, TRAP-deficient P. berghei parasites are less able to activate LatTGF-β than wild-type parasites and their replication is attenuated in vitro. We show that activation of TGF-β by malaria parasites is a two step process involving TSP-like molecules and metalloproteinase activity. Activation of LatTGF-β represents a novel mechanism for direct modulation of the host response by malaria parasites.
The Role of Brg1, a Catalytic Subunit of Mammalian Chromatin-remodeling Complexes, in T Cell Development
Authors: Gebuhr Thomas C. , Kovalev Grigoriy I. , Bultman Scott , Godfrey Virginia , Su Lishan , Magnuson Terry
Published: December 2003

Mammalian SWI–SNF-related complexes use brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes and regulate transcription. Recent biochemical data has linked Brg1 function to genes important for T lymphocyte differentiation. To investigate the role of SWI–SNF-related complexes in this lineage, we ablated Brg1 function in T lymphocytes. T cell–specific Brg1-deficient mice showed profound thymic abnormalities, CD4 derepression at the double negative (DN; CD4− CD8−) stage, and a developmental block at the DN to double positive (CD4+ CD8+) transition. 5′-bromo-2′-deoxyuridine incorporation and annexin V staining establish a role for Brg1 complexes in the regulation of thymocyte cell proliferation and survival. This Brg1-dependent cell survival is specific for developing thymocytes as indicated by the presence of Brg1-deficient mature T lymphocytes that have escaped the developmental block in the thymus. However, reductions in peripheral T cell populations lead to immunodeficiency and compromised health of mutant mice. These results highlight the importance of chromatin-remodeling complexes at different stages in the development of a mammalian cell lineage.
IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells
Authors: Li JiChu , Huston Gail , Swain Susan L.
Published: December 2003

After transfer to adoptive hosts, in vitro–generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown. We find that low doses of interleukin (IL) 7 enhance survival of effectors in vitro without driving their division. When in vitro–generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype. CD4 effectors generated from wild-type versus IL-7 receptor−/− mice were transferred to adoptive hosts, including intact mice and those deficient in IL-7. In each case, the response to IL-7 was critical for good recovery of donor cells after 5–7 d. Recovery was also IL-7–dependent in Class II hosts where division was minimal. Blocking antibodies to IL-7 dramatically decreased short-term recovery of transferred effectors in vivo without affecting their division. These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.
CD226 (DNAM-1) Is Involved in Lymphocyte Function–associated Antigen 1 Costimulatory Signal for Naive T Cell Differentiation and Proliferation
Authors: Shibuya Kazuko , Shirakawa Jun , Kameyama Tomie , Honda Shin-ichiro , Tahara-Hanaoka Satoko , Miyamoto Akitomo , Onodera Masafumi , Sumida Takayuki , Nakauchi Hiromitsu , Miyoshi Hiroyuki , Shibuya Akira
Published: December 2003

Upon antigen recognition by the T cell receptor, lymphocyte function–associated antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells (Ths) inhibited interleukin (IL)-12–independent Th1 development initiated by CD3 and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T cells in the absence of IL-2. These results suggest that CD226 is involved in LFA-1–mediated costimulatory signals for triggering naive T cell differentiation and proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover, proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1 costimulatory signal is independent of lipid rafts in CD8+ T cells.
The Tumor Suppressor CYLD Interacts with TRIP and Regulates Negatively Nuclear Factor κB Activation by Tumor Necrosis Factor
Authors: Regamey Alexandre , Hohl Daniel , Liu Jia Wei , Roger Thierry , Kogerman Priit , Toftgård Rune , Huber Marcel
Published: December 2003

Cylindromas are benign adnexal skin tumors caused by germline mutations in the CYLD gene. In most cases the second wild-type allele is lost in tumor tissue, suggesting that CYLD functions as tumor suppressor. CYLD is a protein of 956 amino acids harboring a functional deubiquitinating domain at the COOH-terminal end. To shed more light on the function of CYLD, we have performed a yeast two hybrid screen using an HaCaT cDNA library that identified the RING finger protein TRIP (TRAF-interacting protein) as interactor with full-length CYLD. Mapping of the interacting domains revealed that the central domain of CYLD binds to the COOH-terminal end of TRIP. Far Western analysis and coimmunoprecipitations in mammalian cells confirmed that full-length CYLD binds to the COOH-terminal domain of TRIP. Because TRIP is an inhibitor of nuclear factor (NF)-κB activation by tumor necrosis factor (TNF), the effect of CYLD on NF-κB activation was investigated in HeLa cells. The results established that CYLD down-regulates NF-κB activation by TNF-α. The inhibition by CYLD depends on the presence of the central domain interacting with TRIP and its deubiquitinating activity. These findings indicate that cylindromas arise through constitutive NF-κB activation leading to hyperproliferation and tumor growth.
Abnormal Mammary Gland Development and Growth Retardation in Female Mice and MCF7 Breast Cancer Cells Lacking Androgen Receptor
Authors: Yeh Shuyuan , Hu Yueh-Chiang , Wang Peng-Hui , Xie Chao , Xu Qingquan , Tsai Meng-Yin , Dong Zhihong , Wang Ruey-Sheng , Lee Ting-Hein , Chang Chawnshang
Published: December 2003

Phenotype analysis of female mice lacking androgen receptor (AR) deficient (AR−/−) indicates that the development of mammary glands is retarded with reduced ductal branching in the prepubertal stages, and fewer Cap cells in the terminal end buds, as well as decreased lobuloalveolar development in adult females, and fewer milk-producing alveoli in the lactating glands. The defective development of AR−/− mammary glands involves the defects of insulin-like growth factor I–insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK) signals as well as estrogen receptor (ER) activity. Similar growth retardation and defects in growth factor–mediated Ras/Raf/MAPK cascade and ER signaling are also found in AR−/− MCF7 breast cancer cells. The restoration assays show that AR NH2-terminal/DNA-binding domain, but not the ligand-binding domain, is essential for normal MAPK function in MCF7 cells, and an AR mutant (R608K), found in male breast cancer, is associated with the excessive activation of MAPK. Together, our data provide the first in vivo evidence showing that AR-mediated MAPK and ER activation may play important roles for mammary gland development and MCF7 breast cancer cell proliferation.
Requirement for Ras Guanine Nucleotide Releasing Protein 3 in Coupling Phospholipase C-γ2 to Ras in B Cell Receptor Signaling
Authors: Oh-hora Masatsugu , Johmura Sachiko , Hashimoto Ari , Hikida Masaki , Kurosaki Tomohiro
Published: December 2003

Two important Ras guanine nucleotide exchange factors, Son of sevenless (Sos) and Ras guanine nucleotide releasing protein (RasGRP), have been implicated in controlling Ras activation when cell surface receptors are stimulated. To address the specificity or redundancy of these exchange factors, we have generated Sos1/Sos2 double- or RasGRP3-deficient B cell lines and determined their ability to mediate Ras activation upon B cell receptor (BCR) stimulation. The BCR requires RasGRP3; in contrast, epidermal growth factor receptor is dependent on Sos1 and Sos2. Furthermore, we show that BCR-induced recruitment of RasGRP3 to the membrane and the subsequent Ras activation are significantly attenuated in phospholipase C-γ2–deficient B cells. This defective Ras activation is suppressed by the expression of RasGRP3 as a membrane-attached form, suggesting that phospholipase C-γ2 regulates RasGRP3 localization and thereby Ras activation.
HIV-1 Viremia Prevents the Establishment of Interleukin 2–producing HIV-specific Memory CD4+ T Cells Endowed with Proliferative Capacity
Authors: Younes Souheil-Antoine , Yassine-Diab Bader , Dumont Alain R. , Boulassel Mohamed-Rachid , Grossman Zvi , Routy Jean-Pierre , Sékaly Rafick-Pierre
Published: December 2003

CD4+ T cell responses are associated with disease control in chronic viral infections. We analyzed human immunodeficiency virus (HIV)-specific responses in ten aviremic and eight viremic patients treated during primary HIV-1 infection and for up to 6 yr thereafter. Using a highly sensitive 5-(and-6)-carboxyfluorescein diacetate-succinimidyl ester–based proliferation assay, we observed that proliferative Gag and Nef peptide-specific CD4+ T cell responses were 30-fold higher in the aviremic patients. Two subsets of HIV-specific memory CD4+ T cells were identified in aviremic patients, CD45RA− CCR7+ central memory cells (Tcm) producing exclusively interleukin (IL)-2, and CD45RA− CCR7− effector memory cells (Tem) that produced both IL-2 and interferon (IFN)-γ. In contrast, in viremic, therapy-failing patients, we found significant frequencies of Tem that unexpectedly produced exclusively IFN-γ. Longitudinal analysis of HIV epitope–specific CD4+ T cells revealed that only cells that had the capacity to produce IL-2 persisted as long-term memory cells. In viremic patients the presence of IFN-γ–producing cells was restricted to periods of elevated viremia. These findings suggest that long-term CD4+ T cell memory depends on IL-2–producing CD4+ T cells and that IFN-γ only–producing cells are short lived. Our data favor a model whereby competent HIV-specific Tcm continuously arise in small numbers but under persistent antigenemia are rapidly induced to differentiate into IFN-γ only–producing cells that lack self-renewal capacity.
Global Gene Expression Responses of Fission Yeast to Ionizing Radiation
Authors: Watson Adam , Mata Juan , Bähler Jürg , Carr Anthony , Humphrey Tim
Published: December 2003

A coordinated transcriptional response to DNA-damaging agents is required to maintain genome stability. We have examined the global gene expression responses of the fission yeast Schizosaccharomyces pombe to ionizing radiation (IR) by using DNA microarrays. We identified ∼200 genes whose transcript levels were significantly altered at least twofold in response to 500 Gy of gamma IR in a temporally defined manner. The majority of induced genes were core environmental stress response genes, whereas the remaining genes define a transcriptional response to DNA damage in fission yeast. Surprisingly, few DNA repair and checkpoint genes were transcriptionally modulated in response to IR. We define a role for the stress-activated mitogen-activated protein kinase Sty1/Spc1 and the DNA damage checkpoint kinase Rad3 in regulating core environmental stress response genes and IR-specific response genes, both independently and in concert. These findings suggest a complex network of regulatory pathways coordinate gene expression responses to IR in eukaryotes.
Normal Pressure Hydrocephalus and Cerebral Blood Flow: A PET Study of Baseline Values
Authors: Owler Brian K. , Momjian Shahan , Czosnyka Zofia , Czosnyka Marek , Péna Alonso , Harris Neil G. , Smielewski Piotr , Fryer Tim , Donovan Tim , Coles Jonathon , Carpenter Adrian , Pickard John D.
Published: December 2003

Regional cerebral blood flow (CBF) was studied with O15-water positron emission tomography and anatomic region-of-interest analysis on coregistered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.
Neuroprotection after Transient Global Cerebral Ischemia in Wlds Mutant Mice
Authors: Gillingwater Thomas H. , Haley Jane E. , Ribchester Richard R. , Horsburgh Karen
Published: December 2003

The Wlds mouse mutant demonstrates a remarkable phenotype of delayed axonal and synaptic degeneration after nerve lesion. In this study, the authors tested the hypothesis that expression of Wld protein is neuroprotective in an in vivo mouse model of global cerebral ischemia. This model is associated with selective neuronal degeneration in specific brain regions such as the caudate nucleus and CA2 hippocampal pyramidal cell layer. The extent of neuronal damage was quantified in Wlds compared to wild-type mice after an identical episode of global cerebral ischemia. The results demonstrated a significant and marked reduction in the extent of neuronal damage in Wlds as compared to wild-type C57Bl/6 mice. In the caudate nucleus, Wld expression significantly reduced the percentage of ischemic neuronal damage after global ischemia (Wlds, 27.7 ± 16.8%; wild-type mice, 58.7 ± 32.3%; P = 0.036). Similarly, in the CA2 pyramidal cell layer, there was a significant reduction of neuronal damage in the Wlds mice as compared to wild-type mice after ischemia (Wlds, 17.7 ± 23.0%; wild-type mice, 41.9 ± 28.0%; P < 0.023). Thus, these results clearly demonstrate that the Wld gene confers substantial neuroprotection after cerebral ischemia, and suggest a new role to that previously described for Wlds.
Molecular Profile of Vascular Ion Channels after Experimental Subarachnoid Hemorrhage
Authors: Aihara Yasuo , Jahromi Babak S. , Yassari Reza , Nikitina Elena , Agbaje-Williams Mayowa , Macdonald R. Loch
Published: December 2003

Cerebral vasospasm is a transient, delayed constriction of cerebral arteries that occurs after subarachnoid hemorrhage (SAH). Smooth muscle cells show impaired relaxation after SAH, which may be caused by a defect in the ionic mechanisms regulating smooth muscle membrane potential and Ca2+ permeability. We tested this hypothesis by examining changes in expression of mRNA and protein for ion channels in the basilar arteries of dogs after SAH using quantitative real-time polymerase chain reaction (PCR) and western blotting. SAH was associated with a significant reduction in basilar artery diameter to 41 ± 8% of pre-SAH diameter ( P < 0.001) after 7 days. There was significant downregulation of the voltage-gated K+ channel Kv 2.2 (65% reduction in mRNA, P < 0.001; 49% reduction in protein, P < 0.05) and the β1 subunit of the large-conductance, Ca2+-activated K+ (BK) channel (53% reduction in mRNA, P < 0.02). There was no change in BK β1 subunit protein. Changes in mRNA levels of Kv 2.2 and the BK-β1 subunit correlated with the degree of vasospasm (r2 = 0.490 and 0.529 respectively, P < 0.05). The inwardly rectifying K+ (Kir) channel Kir 2.1 was upregulated (234% increase in mRNA, P < 0.001; 350% increase in protein, P < 0.001). There was no significant change in mRNA expression of L- type Ca2+ channels and the BK-α subunit. These data suggest that K+ channel dysfunction may contribute to the pathogenesis of cerebral vasospasm.
Educating managers for decision making and leadership
Authors: Vroom Victor H.
Published: December 2003

This paper describes a research program, spanning three decades, on the development of a model of leadership style – specifically, the form and degree to which managers should involve team members in decision making. The model distinguishes five levels of participation and, in its current form, 11 situational factors which influence the effects of participation on decision quality, implementation, time, and team development. Pencil and paper and computer‐based representations of the model are described and compared. Finally, the paper concludes with a discussion of the use of the model in management development. Based on experience in training managers in many countries around the world, the author argues that didactic expositions of the model are largely ineffective in producing behavior change unless accompanied by experiential activities which enable managers to examine their own implicit assumptions about the consequences of sharing their decision making power.
Guidelines for management and leadership decision
Authors: Rausch Erwin
Published: December 2003

This paper presents an eight‐questions model for leadership and management decisions. The eight questions provide a comprehensive and integrated system that can help managers become more competent as managers, and as leaders, by bringing more thoroughly considered decisions. They are based on managerial responsibilities and on existing motivation and leadership theories, as reported in the literature. Managers who develop the habit to ask these eight question with all decisions that affect stakeholders, will find them easy to apply as guidelines to better decisions. The model also applies to individuals who are not in managerial positions but find themselves in leadership roles in teams or projects at work, in their professions, or at home. For thinking about leadership and managerial functions, and for higher education and human resource development, the eight‐questions model provides a more practical and actionable guide than the Fayol cycle of planning, organizing, leading (or influencing or directing), and controlling, that has been a foundation concept for more than 80 years.
Intuition in decisions
Authors: Patton John R.
Published: December 2003

To maintain and sustain competitive work organizations, leadership is necessary to help organizations develop a new vision, and rapidly manage organizational change to position themselves for pursuit of the new vision. Leaders need competent and motivated employees to serve as the catalysts of change as the workforce is mobilized to shift gears and adapt to a changing environment. Part of the changing environment is the Internet and the global economy where the speed of communications and business transactions has increased tremendously. It leaves decisive leaders with no choice in extraordinary circumstances other than to make decisions without all of the data and the time to consult with others. This paper summarizes relevant literature and analyzes some previously suggested foundations for intuitive knowledge. It offers a simplification of these presumed sources and suggests what education, leadership development and self‐development might do to bring about planned improvement in intuitive decision‐making. It concludes with some implications for the future.
Discovery mindset: a decision‐making model for discovery and collaboration
Authors: Benson Joy , Dresdow Sally
Published: December 2003

This paper explores a mental model for decision making that is focused on discovery and collaboration. The model consists of six components: self‐awareness, development orientation, systems perspective, emotional orientation, complexity dynamics, and generative conversation. As an interactive model, the components create a mental frame that enables the decision maker to achieve greater insight and develop creative opportunities that enhance the ability to see decision‐making as a complex process.
Leadership, decision making, and organizational justice
Authors: Tatum B. Charles , Eberlin Richard , Kottraba Carin , Bradberry Travis
Published: December 2003

The article integrates three lines of research with regard to leadership, decision making, and organizational justice. First the theoretical perspective, it is argued that transformational and transactional leaders adopt different approaches to decision making. Transformational leaders appear to prefer a comprehensive style of decision making that uses many input sources and considers many optional pathways. Transactional leaders, by contrast, are more prone to use a more limited information base, and consider fewer alternative routes. The study reported on here concludes that transformational and transactional leaders focus on different aspects of organizational justice. Transformational leaders tend to emphasize the social dimensions of fairness in the workplace. Transactional leaders are oriented toward the structural features of workplace justice. Some practical issues are addressed, such as what should be considered when managers are selected for specific assignments with leadership requirements, and issues pertaining to changing leadership styles.
Does sex of the leader and subordinate influence a leader’s disciplinary decisions?
Authors: Bisking Robert D. , Ree Malcolm , Green Mark , Odom Lamar
Published: December 2003

This study, conducted in 2002, investigated the impact of sex on a leader’s decisions involving employee disciplinary situations. All leaders would like to believe that they make fair and impartial decisions. Some of the most difficult decisions leaders make involve people (i.e. subordinates), because careers may be at risk. This research examined the impact sex may have on decisions made by leaders in four different disciplinary scenarios, sexual harassment, drug test violation, insubordination and theft. A scenario‐based survey instrument, developed by the author, and the Bem Sex‐Role Instrument (BSRI) short‐form, were used in the data collection. It was determined from the data collected that the sex of the employee was an influence in decision making and that the sex of the leader (i.e. decision maker) was of no influence. It was further determined that the BSRI Femininity and Masculinity scores were not accurate predictors of disciplinary actions.
Gender influences in decision‐making processes in top management teams
Authors: Klenke Karin
Published: December 2003

Top management teams (TMT) were initially introduced almost 20 years ago but recently have rekindled the interest of researchers whose experience with organizations has demonstrated that the arrangement of the single omnipotent CEO at the apex of the firm has outlived its utility at a time when it is impossible for one individual to command all the knowledge necessary to effectively lead an organization. This article describes a model that examines gender related influences, which are hypothesized to affect the decision making process in TMTs. More specifically, it is postulated here that it is not genderper sethat accounts for differences in decision making among senior female and male executives, but that four constructs, namely power, political savvy, conflict management and trust mediate the hypothesized relationships explicated in the model. Implications for increased participation of women on TMTs are explored.
Explaining executive integrity: governance, charisma, personality and agency
Authors: Tourigny Louise , Dougan William L. , Washbush John , Clements Christine
Published: December 2003

The recent significant occurrences of dysfunctional, and perhaps unethical, decision making and actions by a number of highly successful corporate executives suggest that there are systematic explanations for the questionable managerial behaviors that go beyond simple attributions of individual character flaws. This paper draws from four management research streams to identify some enabling conditions that constitute plausible mechanisms that may have exacerbated the present situation. Research traditions include the literature pertaining to the primacy of the rights of shareholders in equity capital financed corporate organizations, the literature describing the mechanisms whereby charisma is socially constructed and institutionalized, the literature attributing the gravitation toward positions of power on the part of individuals with predispositions to act in an unethical manner and the literature describing conditions which limit the ability of principals to fully specify the provisions of contracts with agents who are in positions of control of corporate organizations.
CEO and ethical reputation: visionary or mercenary?
Authors: Stanwick Peter A. , Stanwick Sarah D.
Published: December 2003

This study examines the relationship between ethical reputation, CEO compensation and firm performance for the top corporate citizens as rated by Business Ethics magazine. The results show that there was not a direct relationship between CEO compensation and firm performance, that a high level of CEO compensation combined with a high ethical reputation did not impact the financial performance of the firm, and firms with a high ethical reputation had only average financial results, while firms with low ethical reputations displayed both high and low financial performance. Furthermore, CEOs of unfirms had, on average, higher compensation levels than firms that were profitable. These findings bring useful inputs for CEO on how they can justify high levels of compensation even during periods when the firm is not profitable or has a low level of profitability. An interesting sidelight of the study is that three CEOs in the sample whose firms were profitable did not accept any compensation during 2002, probably because the financial performance was below expectations.
Management by site‐based teams: a statistical approach
Authors: Predmore Carolyn E. , Khelfaoui Salah E. , Serio Anthony
Published: December 2003

There is a constant evaluation of managerial techniques ranging from the military leadership style to self‐motivated self‐management. Team management has gone from an American concept, to a Japanese enhanced technique back to a US management and leadership tool. It can be useful for both traditional businesses as well as non‐profit organizations such as educational institutions. Teams comprised of administrators, teachers, parents, and staff (and students when age appropriate) can effectively drive the site‐based management shared decision making approach to restructure education. Working as a team is very complex and requires training for the participants for the team to work well together and to thrive. This study looks at identifying factors and variables for team building that can bring good team function as a basis for sound leadership decisions. It was found that incorporating representatives of each of the stakeholder groups was essential for the creation of effective team‐based management. Respect for the foci of the various stakeholder groups is critical to the application of the leadership decisions of the teams.
Leadership theory and practice: a “case” in point
Authors: Armandi Barry , Oppedisano Jeannette , Sherman Herbert
Published: December 2003

Leadership theory has little value if it cannot be applied to real world situations. A summary review of the literature on leadership theory is provided here first. A disguised real case concerning Ted Shade, a Vice‐President at Galactic Chips, Inc. is then provided which describes a manager who is extremely task‐oriented. The case analysis follows. It includes questions and answers which connect leadership theory to case specifics and requires learners to analyze the case using differing leadership models.
A Bayesian Non‐parametric Approach to Survival Analysis Using Polya Trees
Authors: Muliere Pietro , Walker Stephen
Published: December 2003

This paper presents a Bayesian non‐parametric approach to survival analysis based on arbitrarily right censored data. The analysis is based on posterior predictive probabilities using a Polya tree prior distribution on the space of probability measures on [0, ∞). In particular we show that the estimate generalizes the classical Kaplanndash;Meier non‐parametric estimator, which is obtained in the limiting case as the weight of prior information tends to zero.
A Score Test for the Multivariate Burr and Other Weibull Mixture Distributions
Authors: Crowder Martin , Kimber Alan
Published: December 2003

The p‐variate Burr distribution has been derived, developed, discussed and deployed by various authors. In this paper a score statistic for testing independence of the components, equivalent to testing for p independent Weibull against a p‐variate Burr alternative, is obtained. Its null and non‐null properties are investigated with and without nuisance parameters and including the possibility of censoring. Two applications to real data are described. The test is also discussed in the context of other Weibull mixture models.
Singly and Doubly Censored Current Status Data: Estimation, Asymptotics and Regression
Authors: Van Der Laan Mark J. , Bickel Peter J. , Jewell Nicholas P.
Published: December 2003

In biostatistical applications interest often focuses on the estimation of the distribution of time between two consecutive events. If the initial event time is observed and the subsequent event time is only known to be larger or smaller than an observed point in time, then the data is described by the well‐understood singly censored current status model, also known as interval censored data, case I. Jewell et al. (1994) extended this current status model by allowing the initial time to be unobserved, with its distribution over an observed interval [A, B] known; the data is referred to as doubly censored current status data. This model has applications in AIDS partner studies. If the initial time is known to be uniformly distribute d, the model reduces to a submodel of the current status model with the same asymptotic information bounds as in the current status model, but the distribution of interest is essentially the derivative of the distribution of interest in the current status model. As a consequence the non‐parametric maximum likelihood estimator is inconsistent. Moreover, this submodel contains only smooth heavy tailed distributions for which no moments exist. In this paper, we discuss the connection between the singly censored current status model and the doubly censored current status model (for the uniform initial time) in detail and explain the difficulties in estimation which arise in the doubly censored case. We propose a regularized MLE corresponding with the current status model. We prove rate results, efficiency of smooth functionals of the regularized MLE, and present a generally applicable efficient method for estimation of regression parameters, which does not rely on the existence of moments. We also discuss extending these ideas to a non‐uniform distribution for the initial time.
Simultaneous Confidence Intervals for the Difference of Two Survival Functions
Authors: Parzen M. I. , Wei L. J. , Ying Z.
Published: December 2003

In comparing two treatments with failure time observations, confidence bands for the “difference” of two survival curves provide useful information about a global picture of the treatment difference over time. In this note, we propose a rather simple procedure for constructing such simultaneous confidence intervals. Our technique can also be used in the one‐sample case, which has been extensively studied in the literature.
Experimental systemic contact dermatitis from nickel: a dose–response study
Authors: Jensen Christian S. , Menné Torkil , Lisby Steen , Kristiansen Jesper , Veien Niels K.
Published: December 2003

Systemic contact dermatitis is usually seen as flare‐up of previous dermatitis or de novo dermatitis similar to allergic contact dermatitis. Although systemic contact dermatitis from medicaments is a well‐established entity, the existence of clinically relevant systemic reactions to oral nickel exposure, in particular systemic reactions to nickel in the daily diet, remains controversial. Several studies have shown that oral exposure to nickel can induce systemic contact dermatitis in nickel‐sensitive individuals. In most of these studies, however, the exposure dose of nickel used has been considerably higher than the nickel content in the normal daily diet. The aim of the current investigation was to study dose–response dependency of oral exposure to nickel. In a double‐blind, placebo‐controlled oral exposure trial, 40 nickel‐sensitive persons and 20 healthy (non‐nickel‐sensitive) controls were given nickel sulfate hexahydrate in doses similar to and greater than the amount of nickel ingested in the normal Danish daily diet. The nickel content in urine and serum before and after oral exposure was measured to determine nickel uptake and excretion. The influence of the amount of nickel ingested on the clinical reactions to oral exposure and on nickel concentrations in serum and urine was evaluated. Among nickel‐sensitive individuals, a definite dose–response dependency was seen, following oral exposure to nickel. 7 of 10 nickel‐sensitive individuals had cutaneous reactions to oral exposure to 4.0 mg nickel, an amount approximately 10 times greater than the estimated normal daily dietary intake of nickel. 4 of 10 nickel‐sensitive individuals had cutaneous reactions to 1.0 mg nickel, a dose which is close to the estimated maximum amount of nickel contained in the daily diet. 4 of 10 nickel‐sensitive individuals reacted to 0.3 mg nickel or to the amount equivalent to that contained in a normal daily diet, and 1 of 10 reacted to a placebo. None of the 20 healthy controls had cutaneous reactions to 4.0 mg nickel or to a placebo. Prior to oral exposure, there was no measurable difference in the amount of nickel in the urine or serum of nickel‐sensitive persons and healthy controls. Following the oral challenge, the nickel content in the urine and serum of both nickel‐sensitive and healthy control individuals was directly related to the dose of nickel ingested.
A stronger patch test elicitation reaction to the allergen hydroxycitronellal plus the irritant sodium lauryl sulfate
Authors: Heydorn S. , Andersen K. E. , Johansen J. D. , Menné T.
Published: December 2003

Household and cleaning products often contain both allergens and irritants. The aim of this double‐blinded, randomized, paired study was to determine whether patch testing with an allergen (hydroxycitronellal) combined with an irritant [sodium lauryl sulfate (SLS)] cause a stronger patch test elicitation reaction than patch testing with the allergen (hydroxycitronellal) alone, in patients previously patch tested positive to hydroxycitronellal. A stronger patch test elicitation reaction was defined as at least 1 day of patch test reading showing more positive patch tests (+, ++ or +++) on the forearm patch tested with 6 concentrations of SLS plus hydroxycitronellal than on the forearm tested with 6 concentrations of hydroxycitronellal alone and no day of patch test readings showing more positive tests on the hydroxycitronellal forearm. 15/20 (75%) had at least 1 day of patch test reading with more positive patch tests on the forearm patch tested with SLS plus hydroxycitronellal and no day of patch test readings with more positive patch tests on the forearm tested with hydroxycitronellal (P = 0.0253). Estimation of the blood flow with laser Doppler supported these findings.
Quantitative risk assessment for the induction of allergic contact dermatitis: uncertainty factors for mucosal exposures
Authors: Farage Miranda A. , Bjerke Donald L. , Mahony Catherine , Blackburn Karen L. , Gerberick G. Frank
Published: December 2003

The quantitative risk assessment (QRA) paradigm has been extended to evaluating the risk of induction of allergic contact dermatitis from consumer products. Sensitization QRA compares product‐related, topical exposures to a safe benchmark, the sensitization reference dose. The latter is based on an experimentally or clinically determined ‘no observable adverse effect level’ (NOAEL) and further refined by incorporating ‘sensitization uncertainty factors’ (SUFs) that address variables not adequately reflected in the data from which the threshold NOAEL was derived. A critical area of uncertainty for the risk assessment of oral care or feminine hygiene products is the extrapolation from skin to mucosal exposures. Most sensitization data are derived from skin contact, but the permeability of vulvovaginal and oral mucosae is greater than that of keratinized skin. Consequently, the QRA for some personal products that are exposed to mucosal tissue may require the use of more conservative SUFs. This article reviews the scientific basis for SUFs applied to topical exposure to vulvovaginal and oral mucosae. We propose a 20‐fold range in the default uncertainty factor used in the contact sensitization QRA when extrapolating from data derived from the skin to situations involving exposure to non‐keratinized mucosal tissue.
Use of the local lymph node assay in the evaluation of the sensitizing potential of pharmaceutical process intermediates
Authors: Durand Geneviève , De Burlet Georges , Virat Michel , Nauman Bruce D.
Published: December 2003

The murine local lymph node assay (LLNA) has recently been developed to determine the contact sensitization potential of chemicals. Since its original development, the LLNA results have been the subject of extensive comparisons with guinea pig and human data. The investigations described here were designed to explore the ability of the LLNA to identify accurately, pharmaceutical process intermediates (PIs) known to cause contact allergy in humans. To that end, 16 PIs previously tested in the guinea‐pig maximization test (GPMT) were tested in the LLNA. Another PI known to be a contact sensitizer in humans was tested only in the LLNA. Cases of contact sensitization in humans were reported only for PIs that were extreme sensitizers in the GPMT and had low EC3 values (concentration of the test substance required to generate a threefold increase in lymph node cell proliferation) in the LLNA. These data provide additional evidence that the LLNA is able to discriminate skin sensitizers from chemicals that do not possess a significant skin sensitization potential and is thus a useful method for hazard identification. In addition, this method also offers important animal welfare benefits and may also be useful for risk assessment purposes.
Systemic acyclovir reaction subsequent to acyclovir contact allergy: which systemic antiviral drug should then be used?
Authors: Vernassiere C. , Barbaud A. , Trechot P. H. , Weber‐Muller F. , Schmutz J. L.
Published: December 2003

Allergic contact dermatitis caused by acyclovir is rare. We report the 5th case of systemic acyclovir reaction subsequent to acyclovir contact dermatitis, with investigations made to determine an alternative antiviral treatment. A 23‐year‐old woman, after dermatitis while using Zovirax® cream, went on to develop urticaria after oral acyclovir. Patch tests were performed with the components of Zovirax® cream (acyclovir, propylene glycol and sodium lauryl sulfate) and with other antiviral drugs. Patch tests were positive to Zovirax® cream, acyclovir, valacyclovir and propylene glycol. Patch and prick tests with famciclovir were negative, but its oral administration caused an itchy erythematous dermatitis on the trunk and extremities. Our patient developed a systemic acyclovir reaction subsequent to acyclovir allergic contact dermatitis, with cross‐reactions to valacyclovir and famciclovir. Their common chemical structure is the 2‐aminopurine nucleus. It is probably this part of the molecule that provokes both contact allergy and systemic reactions. The only antiviral drugs not having this core are foscarnet and cidofovir, and these could therefore be alternatives.
Nonanoic acid – an experimental irritant
Authors: Wahlberg Jan E. , Lindberg Magnus
Published: December 2003

Irritant contact dermatitis is defined as a non‐immunological skin reaction following exposure to various chemical, mechanical and physical factors. It is known that the skin response to irritants depends on the irritant applied and differs between chemically different irritants. Sodium lauryl sulfate (SLS) is an anionic detergent and the most frequently used substance in experimental irritant contact dermatitis. In 1980, it was suggested that nonanoic acid (NNA) could be used as a positive control when patch testing. Since then, NNA has been used as an experimental irritant in several studies and has been used as a chemically different substance compared to SLS. The present article presents a review of the application of NNA in studies on skin irritancy and experimental irritant contact dermatitis.
Development of methods to enhance extrinsic tooth discoloration for comparison of toothpastes
Authors: Pontefract H. , Courtney M. , Smith S. , Newcombe R. G. , Addy M.
Published: December 2003

Background: Extrinsic staining of teeth is considered to be unsightly and a number of ‘whitening’ toothpastes have been formulated to inhibit or remove such tooth discoloration. The aim of this study was to compare the stain prevention of two toothpastes.

Method: The study was a single‐blind, randomised, placebo‐controlled, crossover design, balanced for residual effects involving 24 healthy dentate volunteers. The treatments were as follows: (1) a whitening toothpaste product, (2) an experimental toothpaste formulation and (3) water. For each 4‐day rinse period, subjects were rendered stain free on the teeth and tongue. Approximately on the hour from 09:00 to 16:00 hours, subjects rinsed with chlorhexidine mouth rinse for 1 min followed by warm black tea for 1 min. The treatment interventions were at 09:00 and 16:00 hours and before the chlorhexidine rinse. The toothpastes were rinsed as 3 g/10 ml water slurries and water as a 10 ml rinse each for 2 min. On day 5, subjects were scored for tooth and tongue stain intensity and area, and the product of these was calculated. The washout period was at least 9 days.

Results: Treatment differences for the teeth were highly significant but not for the tongue. Paired contrasts for tooth stain intensity, area and product were mostly all significantly in favour of reduced staining by the experimental formulation compared with water and the whitening product. There were no significant differences between water and the whitening product.

Conclusions: Using a forced dietary staining method, the data support a tooth stain‐inhibitory/‐removal action for the experimental formulation, but not the whitening product.