bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation and Cellular Immune Responses in Abdominal Aortic Aneurysms
Authors: Shimizu Koichi , Mitchell Richard N. , Libby Peter
Published: February 2006

Expansion and rupture of abdominal aortic aneurysms (AAA) result in high morbidity and mortality rates. Like stenotic atherosclerotic lesions, AAA accumulate inflammatory cells, but usually exhibit much more extensive medial damage. Leukocyte recruitment and expression of pro-inflammatory Th1 cytokines typically characterize early atherogenesis of any kind, and modulation of inflammatory mediators mutes atheroma formation in mice.1However, the mechanistic differences between stenotic and aneurysmal manifestations of atherosclerosis remain unexplained. We recently showed that aortic allografts deficient in interferon-γ (IFN-γ) signaling developed AAA correlating with skewed Th2 cytokine environments, suggesting important regulatory roles for Th1/Th2 cytokine balance in modulating matrix remodeling and important implications for the pathophysiology of aortic aneurysm and atherosclerosis. Further probing of their distinct aspects of immune and inflammatory responses in vascular diseases should continue to shed new light on the pathophysiologic mechanisms that give rise to aneurysmal versus occlusive manifestations and atherosclerosis.
Intercellular Adhesion Molecule-1 Is Upregulated in Ischemic Muscle, Which Mediates Trafficking of Endothelial Progenitor Cells
Authors: Yoon Chang-Hwan , Hur Jin , Oh Il-Young , Park Kyung-Woo , Kim Tae-Youn , Shin Jae-Hoon , Kim Ji-Hyun , Lee Choon-Soo , Chung June-Key , Park Young-Bae , Kim Hyo-Soo
Published: February 2006

Background—

Trafficking of transplanted endothelial progenitor cells (EPCs) to an ischemic organ is a critical step in neovascularization. This study was performed to elucidate the molecular mechanism of EPC trafficking in terms of adhesion molecules.

Methods and Results—

Using murine hindlimb ischemia model, we examined expressions of E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in ischemic muscle by immunofluorescence. ICAM-1 was overexpressed in ischemic muscle compared with nonischemic muscle, whereas expressions of E-selectin, VCAM-1, and PECAM-1 did not show that much difference. ICAM-1 was also upregulated by hypoxia in murine endothelial cells (ECs) as assessed by immunoblot and flow cytometry. EPCs were attached to ECs specifically through ICAM-1/β-2 integrin interaction in vitro. When EPCs were labeled with fluorescent dye or radioisotope (Tc-99m-HMPAO) and systemically administrated in vivo, EPCs preferentially homed to ischemic muscle. By blocking ICAM-1, EPCs entrapment to ischemic limb in vivo was significantly reduced and neovascularization induced by EPC transplantation was attenuated.

Conclusions—

ICAM-1 is upregulated by ischemia, and this is closely associated with EPCs entrapment to ischemic limb. Our findings suggest that ICAM-1 expression might be important in regulating the process of neovascularization through its ability to recruit EPCs.
Role of Endothelial Nitric Oxide Synthase in the Regulation of SREBP Activation by Oxidized Phospholipids
Authors: Gharavi Nima M. , Baker Nancy A. , Mouillesseaux Kevin P. , Yeung Winnie , Honda Henry M. , Hsieh Xavier , Yeh Michael , Smart Eric J. , Berliner Judith A.
Published: February 2006

Oxidized-1-palmitoyl-2-arachidonyl-
sn
-glycero-3-phosphorylcholine (Ox-PAPC), found in atherosclerotic lesions and other sites of chronic inflammation, activates endothelial cells (EC) to synthesize chemotactic factors, such as interleukin (IL)-8. Previously, we demonstrated that the sustained induction of IL-8 transcription by Ox-PAPC was mediated through the activation of sterol regulatory element–binding protein (SREBP). We now present evidence for the role of endothelial nitric oxide synthase (eNOS) in the activation of SREBP by Ox-PAPC. Ox-PAPC treatment of EC induced a dose- and time-dependent activation of eNOS, as measured by phosphorylation of serine 1177, dephosphorylation of threonine 495, and the conversion of
l
-arginine to
l
-citrulline. Activation of eNOS by Ox-PAPC was regulated through a phosphatidylinositol-3-kinase/Akt-mediated mechanism. These studies also demonstrated that pretreatment of EC with NOS inhibitor,
N
ω
-nitro-
l
-arginine-methyl ester (L-NAME), significantly inhibited Ox-PAPC–induced IL-8 synthesis. Because SREBP activation had been previously shown to regulate IL-8 transcription by Ox-PAPC, we examined the effects of L-NAME on Ox-PAPC–induced SREBP activation. Our data demonstrated that Ox-PAPC–induced SREBP activation and expression of SREBP target genes were significantly reduced by pretreatment with L-NAME. Interestingly, treatment of EC with NO donor,
S
-nitroso-
N
-acetylpenicillamine, did not activate SREBP, suggesting that NO alone was not sufficient for SREBP activation. Rather, our findings indicated that superoxide (O
2
·−
), in combination with NO, regulated SREBP activation by Ox-PAPC. We found that Ox-PAPC treatment generated O
2
·−
through an eNOS-mediated mechanism and that mercaptoethylguanidine, a peroxynitrite scavenger, reduced SREBP activation by Ox-PAPC. Taken together, these findings propose a novel role for eNOS in the activation of SREBP and SREBP-mediated inflammatory processes.
Extracellular Nucleotides and Adenosine Independently Activate AMP-Activated Protein Kinase in Endothelial Cells
Authors: da Silva Cleide Gonçalves , Jarzyna Robert , Specht Anke , Kaczmarek Elzbieta
Published: February 2006

AMP-activated protein kinase (AMPK) plays a key role in the regulation of energy homeostasis and is activated in response to cellular stress, including hypoxia/ischemia and hyperglycemia. The stress events are accompanied by rapid release of extracellular nucleotides from damaged tissues or activated endothelial cells (EC) and platelets. We demonstrate that extracellular nucleotides (ATP, ADP, and UTP, but not UDP) and adenosine independently induce phosphorylation and activation of AMPK in human umbilical vein EC (HUVEC) by the mechanism that is not linked to changes in AMP:ATP ratio. HUVEC express NTPDases, as well as 5′-nucleotidase; hence, nucleotides can be metabolized to adenosine. However, inhibition of 5′-nucleotidase had no effect on ATP/ADP/UTP-induced phospho- rylation of AMPK, indicating that AMPK activation occurred as a direct response to nucleotides. Nucleotide-evoked phosphorylation of AMPK in HUVEC was mediated by P2Y1, P2Y2, and/or P2Y4 receptors, whereas P2Y6, P2Y11, and P2X receptors were not involved. The nucleotide-induced phosphorylation of AMPK was affected by changes in the concentration of intracellular Ca2+and by Ca2+/calmodulin-dependent kinase kinase (CaMKK), although most likely it was not dependent on LKB1 kinase. Adenosine-induced phosphorylation of AMPK was not mediated by P1 receptors but required adenosine uptake by equilibrative nucleoside transporters followed by its (intracellular) metabolism to AMP. Moreover, adenosine effect was Ca2+and CaMKK independent, although probably associated with upstream LKB1. We hypothesize that P2 receptors and adenosine transporters could be novel targets for the pharmacological regulation of AMPK activity and its downstream effects on EC function.
Angioplasty for Symptomatic Intracranial Stenosis
Authors: Marks Michael P. , Wojak Joan C. , Al-Ali Firas , Jayaraman Mahesh , Marcellus Mary L. , Connors John J. , Do Huy M.
Published: February 2006

Background and Purpose—

Medical treatment of symptomatic intracranial stenosis carries a high risk of stroke. This study was done to evaluate the clinical and angiographic outcomes after intracranial angioplasty for this disease.

Methods—

A total of 120 patients with 124 intracranial stenoses were treated by primary angioplasty. All patients had neurologic symptoms (stroke or transient ischemic attack) attributable to intracranial stenoses ≥50%. Angiograms were evaluated before and after angioplasty for the degree of stenosis.

Results—

Pretreatment stenoses varied from 50% to 95% (mean 82.2±10.2). Post-treatment stenoses varied from 0% to 90% (mean 36.0±20.1). There were 3 strokes and 4 deaths (all neurological) within 30 days of the procedure, giving a combined periprocedural stroke and death rate of 5.8%. A total of 116 patients (96.7%) were available for a mean follow-up time of 42.3 months. There were 6 patients who had a stroke in the territory of treatment and 5 additional patients with stroke in other territories. Ten deaths occurred during the follow-up period, none of which were neurological. Including the periprocedural stroke and deaths, this yielded an annual stroke rate of 3.2% in the territory of treatment and a 4.4% annual rate for all strokes.

Conclusion—

Intracranial angioplasty can be performed with a high degree of technical success and a low risk of complications. Long-term clinical follow-up of intracranial angioplasty patients demonstrates a risk of future strokes that compares favorably to patients receiving medical therapy.
Molecular Genetic Analysis of Two Large Kindreds With Intracranial Aneurysms Demonstrates Linkage to 11q24-25 and 14q23-31
Authors: Ozturk Ali K. , Nahed Brian V. , Bydon Mohamad , Bilguvar Kaya , Goksu Ethem , Bademci Gulsah , Guclu Bulent , Johnson Michele H. , Amar Arun , Lifton Richard P. , Gunel Murat
Published: February 2006

Background and Purpose—

Both environmental and genetic factors contribute to the formation, growth, and rupture of intracranial aneurysms (IAs). To search for IA susceptibility genes, we took an outlier approach, using parametric genome-wide linkage analysis in extended IA kindreds in which IA is inherited as a simple Mendelian trait. We hereby present the molecular genetic analysis of 2 such families.

Methods—

For genome-wide linkage analysis, we used a 2-stage approach. First, using gene chips in affected-only analysis, we identified genomic regions that provide maximum theoretical logarithm of odds (lod) scores. Next, to confirm or exclude these candidate loci, we genotyped all available family members, both affected and unaffected, using polymorphic microsatellite markers located within these regions.

Results—

We obtained significant lod scores of 4.3 and 3.00 for linkage to chromosomes 11q24-25 and 14q23-31, respectively.

Conclusions—

Molecular genetic analysis of 2 large IA kindreds confirms linkage to chromosome 11q and 14q, which were suggested to contain IA susceptibility genes in a previous study of Japanese sib pairs. Independent identification of these 2 loci strongly suggests that IA susceptibility genes lie within these regions. While demonstrating the genetic heterogeneity of IA, these results are also an important step toward cloning IA genes and ultimately understanding its pathophysiology.
Extent of Early Ischemic Changes on Computed Tomography (CT) Before Thrombolysis
Authors: Dzialowski Imanuel , Hill Michael D. , Coutts Shelagh B. , Demchuk Andrew M. , Kent David M. , Wunderlich Olaf , von Kummer Rüdiger
Published: February 2006

Background and Purpose—

The significance of early ischemic changes (EICs) on computed tomography (CT) to triage patients for thrombolysis has been controversial. The Alberta Stroke Program Early CT Score (ASPECTS) semiquantitatively assesses EICs within the middle cerebral artery territory using a10-point grading system. We hypothesized that dichotomized ASPECTS predicts response to intravenous thrombolysis and incidence of secondary hemorrhage within 6 hours of stroke onset.

Methods—

Data from the European-Australian Acute Stroke Study (ECASS) II study were used in which 800 patients were randomized to recombinant tissue plasminogen activator (rt-PA) or placebo within 6 hours of symptom onset. We retrospectively assessed all baseline CT scans, dichotomized ASPECTS at ≤7 and >7, defined favorable outcome as modified Rankin Scale score 0 to 2 after 90 days, and secondary hemorrhage as parenchymal hematoma 1 (PH1) or PH2. We performed a multivariable logistic regression analysis and assessed for an interaction between rt-PA treatment and baseline ASPECTS score.

Results—

We scored ASPECTS >7 in 557 and ≤7 in 231 patients. There was no treatment-by-ASPECTS interaction with dichotomized ASPECTS (
P
=0.3). This also applied for the 0- to 3-hour and 3- to 6-hour cohorts. However, a treatment-by-ASPECTS effect modification was seen in predicting PH (0.043 for the interaction term), indicating a much higher likelihood of thrombolytic-related parenchymal hemorrhage in those with ASPECTS ≤7.

Conclusion—

In ECASS II, the effect of rt-PA on functional outcome is not influenced by baseline ASPECTS. Patients with low ASPECTS have a substantially increased risk of thrombolytic-related PH.
Microglia Potentiate Damage to Blood–Brain Barrier Constituents
Authors: Yenari Midori A. , Xu Lijun , Tang Xian Nan , Qiao Yanli , Giffard Rona G.
Published: February 2006

Background—

Blood–brain barrier (BBB) disruption after stroke can worsen ischemic injury by increasing edema and causing hemorrhage. We determined the effect of microglia on the BBB and its primary constituents, endothelial cells (ECs) and astrocytes, after ischemia using in vivo and in vitro models.

Methods and Results—

Primary astrocytes, ECs, or cocultures were prepared with or without added microglia. Primary ECs were more resistant to oxygen-glucose deprivation/reperfusion than astrocytes. ECs plus astrocytes showed intermediate vulnerability. Microglia added to cocultures nearly doubled cell death. This increase was prevented by minocycline and apocynin. In vivo, minocycline reduced infarct volume and neurological deficits and markedly reduced BBB disruption and hemorrhage in mice after experimental stroke.

Conclusions—

Inhibition of microglial activation may protect the brain after ischemic stroke by improving BBB viability and integrity. Microglial inhibitors may prove to be an important treatment adjunct to fibrinolysis.
Brain Stem and Cerebellar Hyperintense Lesions in Migraine
Authors: Kruit Mark C. , Launer Lenore J. , Ferrari Michel D. , van Buchem Mark A.
Published: February 2006

Background and Purpose—

Migraineurs are at increased risk of cerebellar infarcts and supratentorial white matter lesions. The prevalence, frequency, and distribution of infratentorial hyperintense lesions in migraine are unknown.

Methods—

Migraineurs with aura (n=161), without aura (n=134), and controls (n=140) from a population-based sample of adults (30 to 60 years of age) were evaluated with MRI.

Results—

Infratentorial hyperintensities were identified in 13 of 295 (4.4%) migraineurs and in 1 of 140 (0.7%) controls (
P
=0.04). Twelve cases had hyperintensities, mostly bilaterally, in the dorsal basis pontis. Those with infratentorial hyperintensities also had supratentorial white matter lesions more often.

Conclusion—

We found an increased prevalence of infratentorial (mostly pontine) hyperintensities in migraineurs from the general population. This extends the knowledge about vulnerable brain regions and type of lesions in migraine brains. A hemodynamic ischemic pathogenesis is likely, but further research is needed.
Pretreatment Hemostatic Markers of Symptomatic Intracerebral Hemorrhage in Patients Treated With Tissue Plasminogen Activator
Authors: Cocho Dolores , Borrell Montserrat , Martí-Fàbregas Joan , Montaner Joan , Castellanos Mar , Bravo Yolanda , Molina-Porcel Laura , Belvís Roberto , Díaz-Manera Jorge-Alberto , Martínez-Domeño Alejandro , Martínez-Lage María , Millán Mónica , Fontcuberta Jordi , Martí-Vilalta Josep-Lluis
Published: February 2006

Background and Purpose—

Symptomatic intracerebral hemorrhage (ICH) is a major complication of thrombolysis in patients with acute ischemic stroke. We analyzed whether baseline hemostatic markers could predict symptomatic ICH (SICH).

Methods—

In a multicenter study of patients treated with intravenous tissue plasminogen activator (t-PA) within 3 hours of stroke onset, we analyzed the following variables: demographic data, vascular risk factors, blood glucose at admission, time from the onset of symptoms to t-PA infusion, blood pressure, neurological deficit measured by the National Institutes of Health Stroke Scale (NIHSS) score, early signs of ischemia on the baseline computed tomography (CT) scan, and protocol deviations. In blood samples, the following markers of coagulation/fibrinolysis were measured before treatment: fibrinogen, prothrombin fragments 1+2, Factor XIII, Factor VII, α
2
antiplasmin, plasminogen activator inhibitor-1 (PAI-1), and thrombin-activatable fibrinolysis inhibitor. ICH was classified according to the European Cooperative Acute Stroke Study (ECASS) II criteria. SICH was defined as a parenchymal hematoma-1 (PH1) or PH2 type, associated with an increase in ≥4 points on the NIHSS score appearing within 36 hours after infusion.

Results—

We studied 114 patients. Mean age was 68.4±12.7 years, and 61% were men. The median baseline NIHSS score was 14. Mean time to treatment was 153±33 minutes. Eight patients had SICH (7%), and 18 patients (15.7%) had asymptomatic ICH. None of the baseline markers of coagulation/fibrinolysis were associated with SICH. In the multivariate analysis, only NIHSS on admission was an independent risk factor for SICH.

Conclusions—

None of the hemostatic markers analyzed in our study predicted symptomatic cerebral hemorrhage in patients with ischemic stroke treated with t-PA.
Introduction
Authors: Abu-Saad Ismael , Champagne Duane
Published: February 2006

This introduction reviews the historical and political context that provides an essential background for exploring key contemporary issues in Palestinian Arab education in Israel and the Occupied Palestinian Territories. Formal public education in Palestine, from its very beginnings, was never under the control of the Palestinian people but instead, has been controlled by successive colonial/external administrations. This introduction examines how major historical periods have affected the development of Palestinian Arab education from the Ottoman period (1516 to 1917) to the British Mandate period (1917 to 1948) to the post-1948 period after the establishment of Israel, which includes the post-1967 Israeli occupation of the West Bank and Gaza Strip, the Oslo agreement period from 1993 to 2000, and the first and second Palestinian Intifadas.
Law and Education
Authors: Jabareen Yousef T.
Published: February 2006

This article explores the dynamic of the Palestinian legal struggle for equal educational opportunities in Israel. It examines the tension between the Palestinians’ positions on equality, on one hand, and the way the Israeli legal system seems to define equality, on the other hand. The article argues that the Israeli legal system seems to adopt a narrow formal view on educational equality for Palestinian children, a view that is not liable to bring about societal transformation.
Separate but Not Equal
Authors: Golan-Agnon Daphna
Published: February 2006

Palestinian Arab education in Israel receives inferior allocations for training, supervision, nature, and art lessons. In general, the physical conditions in the schools are bad and they lack basic study aids. The Palestinian Arab schools have significantly fewer of the unique programs in which the Ministry of Education invests. But discrimination in budgets and “how many” questions cannot lead to an understanding of the whole picture of inequality. Employing questions and methods used by various waves of feminists to explain and combat inequality between men and women, the author asks, How could the education system benefit from equal representation of the voice of Arab leadership? Borrowing from feminist discourse that raises the importance of the diversity of voices and multiculturalism, the author explores and proposes ways of respecting and reinforcing diverse cultural and national identities in the Israeli education system.
State-Controlled Education and Identity Formation Among the Palestinian Arab Minority in Israel
Authors: Abu-Saad Ismael
Published: February 2006

In many modern nation-states, national identity is not inclusive of all of the state’s citizens; rather, it is limited (in varying degrees) to the members of the dominant group. Because such states are structurally unable to meet indigenous/minority groups’ basic human needs for identity, inclusion, and equality, the formation of ethnically based identity and political organization is a natural alternative. To the extent that such alternatives are considered threatening to the state, it will deal with indigenous/minority groups by developing systems of control, based on varying degrees of force, depending on the state’s claim (or lack thereof) to be “democratic.” In this article, the author examines the role the state educational system plays in identity formation and the state’s system of control among indigenous Palestinian youth in Israel.
Negotiating the Present, Historicizing the Future
Authors: Shalhoub-Kevorkian Nadera
Published: February 2006

Children living in conflict zones witness violence, loss of loved ones, killing, injury, and displacement, experiencing fear and loss of protection in their communities—experiences likely to affect the children for the remainder of their lives. This article examines one aspect of the violent conflict in the Palestinian Occupied Territories-West Bank, the way Palestinian children perceive and react to the effect of Israeli military occupation as reflected in the presence and ongoing construction of the Israeli Separation Wall, illustrating traditional views of children as passive victims of political violence and moving instead to view children as agents of change and mobilization. Via writing compositions, focus group discussions, the children’s own photographs, and participatory observation research data, the author contextualizes both the “extended scene” and the immediate moment(s) of Palestinian children facing the Israeli Separation Wall, letting the children’s own words, narratives, and photos speak for themselves; they do their own witnessing.
How Institutions Form
Authors: Hallett Tim , Ventresca Marc J.
Published: February 2006

This article uses a mid-century text to reengage a late-1970s concept to answer a new century question. The authors return to Alvin Gouldner’s classic (1954) study Patterns of Industrial Bureaucracy to reexamine the “coupling” concept in contemporary institutionalism in a way that engages the following question: How do new institutional forms emerge? Based on Gouldner’s detailed observations of work in a gypsum mine, the authors argue that coupling processes are key mechanisms in the emergence of institutional forms. Examining coupling as a dynamic process and activity helps us to understand how the institution of bureaucracy emerged in the gypsum mine and interacted with previous social orders of authority and control. Gouldner’s account of coupling at the mine is a story of formal and informal power struggles and active conflict over meaning, bringing the process of local institutional formation into sharp relief.
Institutional Analysis and the Paradox of Corporate Social Responsibility
Authors: Campbell John L.
Published: February 2006

This article develops a series of causal propositions specifying the institutional conditions under which firms are likely to act in socially responsible ways, as defined by a standard of minimally acceptable corporate behavior. Little theoretical attention has been paid to understanding the causes of corporate social responsibility (CSR). By using institutional theory to explore the determinants of CSR, this article not only sheds light on a blind spot in the literature on CSR but also weds two literatures that have remained largely isolated from each other.
Lost in Translation
Authors: Boxenbaum Eva
Published: February 2006

This article investigates how a group of Danish business actors translated the American practice of diversity management into a novel managerial practice in Denmark. Their translation process unfolded at three levels: (a) individual preference, (b) strategic reframing, and (c) local grounding. The findings contribute to a better understanding of translation processes and have implications for future research and managerial practice.
Sense Making and the Emergence of a New Form of Market Governance
Authors: Fligstein Neil
Published: February 2006

The problem of sense making is particularly acute when established organizations face a sudden set of changes in their fields. This article offers some conceptual clarification of this issue in several ways in the context of profit-making firms. In these circumstances, managers need to worry about not just competitors but also governments, suppliers, and workers. Because of these complex interdependencies, the process of sense making is accompanied by a search process that may lead managers in directions that are a priori unpredictable. New sets of understandings about how to survive in a market often reflect political compromises between actors that create new cultural conceptions of action. Managers have to sometimes take what systems give in order instead of what they might prefer. The author illustrates these principles in the case of the reorganization of the European defense industry.
Identity, Institutions, and New Work Roles
Authors: Patriotta Gerardo , Lanzara Giovan Francesco
Published: February 2006

In this article, the authors draw on institutional theories of organizations to account for the dynamics that shape workers’ agency and identity during the construction and the operation of a green field automotive factory. Based on a detailed field study, they try to understand the mechanisms that first led to the rise and institutionalization of a specific model of workers’ identity and then caused its subsequent, largely unexpected, collapse. In addressing the link between identity and institutions, the case emphasizes the regulative and constitutive influences of institutions, the role of sense making and cognitive processes in shaping workers’ agency and identity, and the factors leading to the erosion of established institutional practices.
Changing Institutional Logics and Executive Identities
Authors: Meyer Renate E. , Hammerschmid Gerhard
Published: February 2006

In this article, the authors analyze whether and to what extent an “old” administrative orientation is being replaced by a new managerial logic in the Austrian public sector. They illustrate that shifts in institutional logics can be analyzed by the extent to which actors draw on the social identities derived from the competing logics and show that the vocabularies and accounts the actors employ to communicate their identity claims reflect the local translation of global logics.
Identity Work and Meaning Arena
Authors: Westenholz Ann
Published: February 2006

A dominant sociological argument asserts that changes in working life and society in general have affected our identities, with the result of increased individualization and the decline of the “organizational man.” The author is critical of this epochalist claim and argues that it is important to design an approach to analyzing the identities and telling the stories of the current transformation of work and identities that recognizes the processes within working life. This proposal goes beyond a grand-scale epochalist claim about the consequences of the transformation to a postmodern area of identity. As an alternative, the author suggests an analysis of identities, drawing on a relational and social constructivist paradigm. She examines how workers employ elements from widespread identity stories as “raw material” when negotiating emerging identities. Drawing on a qualitative study within the information technology field, the author illustrates what such an analysis of emerging identities might look like.
Five Misunderstandings About Case-Study Research
Authors: Flyvbjerg Bent
Published: February 2006

This article examines five common misunderstandings about case-study research: (a) theoretical knowledge is more valuable than practical knowledge; (b) one cannot generalize from a single case, therefore, the single-case study cannot contribute to scientific development; (c) the case study is most useful for generating hypotheses, whereas other methods are more suitable for hypotheses testing and theory building; (d) the case study contains a bias toward verification; and (e) it is often difficult to summarize specific case studies. This article explains and corrects these misunderstandings one by one and concludes with the Kuhnian insight that a scientific discipline without a large number of thoroughly executed case studies is a discipline without systematic production of exemplars, and a discipline without exemplars is an ineffective one. Social science may be strengthened by the execution of a greater number of good case studies.
The Participant as Ally and Essentialist Portraiture
Authors: Witz Klaus G.
Published: February 2006

This article describes some of the essential features of a methodological approach to studying individuals’ deeper motivations and experiences. The overall approach consists of “interviewing for feeling” with “the participant as ally and co-contemplator,” “conceptually developed essentialist portraiture,” and cross-case discussion, with an epistemology based on C. H. Cooley’s principle of “sympathetic introspection.” The heart of the article is an example of an analysis of excerpts from an interview with an English as a second language teacher regarding her interest in language. The analysis illustrates how to see and conceptualize the manner in which certain essential aspects in the participant’s consciousness and overall orientation evolve in time. This example is then used to illustrate several concerns of portraiture and the epistemological presuppositions of the approach.
Outside the Spoon Drawer, Naked and Skinless in Search of My Professional Esteem
Authors: Leitch Ruth
Published: February 2006

This autoethnography explores the pain and unexpectedness of personal and professional learning in being challenged to find an other “voice” after years of being a “responsible anarchist” within the academy’s traditional expectations. It tells of the emotions in setting forth on a self-chosen quest to uncover and understand the history of the author’s shame as a female academic with management responsibility but without a doctorate until relatively late in her career and some of the ways in which she chose unconsciously to ameliorate this along the way. The commitment to persist with the process of writing that explores emotional resistances born of history, images, and experiences of vulnerability was a deeply personal, embodied experience for the author. Indirectly, the experience of the story demonstrates how writing spontaneously and unknowingly with a desire for self-understanding has the power to uncover what goes on below the surface of experience and identity.
Competing Ethical Communities and a Researcher’s Dilemma
Authors: Dougherty Debbie S. , Atkinson Joshua
Published: February 2006

Ethical research communities provide important guidance for those conducting communication research projects. However, researchers face serious ethical dilemmas when their memberships in multiple ethical communities create conflicting ethical obligations. The present study explores conflicting demands between competing ethical communities to provide a series of reflexive questions researchers can ask themselves as they negotiate the contradictory terrain of their ethical communities. To accomplish this task, the authors explore the ethical dilemmas faced by one researcher as she conducted research on sexual harassment.
Balancing the Berimbau
Authors: Stephens Neil , Delamont Sara
Published: February 2006

This article is an unusual reflexive text. It has two authors, two voices, two embodied experiences, and two sociological biographies in dialogue. The empirical focus is capoeira, but the ethnographic experience is common to many cultural forms. Capoeira is the Brazilian dance and martial art, done to the music of the berimbau. Classes are offered in many European countries, as well as in North America. Two sociologists, one a practitioner, the other a sedentary observer, collaborate to study what attracts students outside Brazil to capoeira, how it is taught to non-Brazilians, and how the classes and social events are enacted and understood. The dualities of the collaborative and contrastive engagements are explored in this article, which focuses on how to do fieldwork on an embodied skill. Physical activity, musical apprenticeship, and a multilingual environment are all made problematic in their collaborative reflections.
Reading and Writing Womanist Poetic Prose
Authors: Borum Valerie
Published: February 2006

Poetic prose—a creative, novel, qualitative technique developed by the author—is used to present in a multivocal, interactive, and interwoven style the findings of in-depth, thematic interviews with 12 African American mothers with deaf daughters. This style of interweaving the voices of participants in a creative prose is indicative of African American cultural and oral tradition. It permits and deepens the reader’s ability to emotionally and spiritually connect with experiences and emotions of African American mothers with deaf daughters. Womanism/Black feminism offers a powerful conceptual framework for organizing and evoking these experiences of women as mothers and girls as daughters.
A Primary Act of Imagination
Authors: Jago Barbara J.
Published: February 2006

This autoethnography details the author’s efforts during the past eight years to write and publish her dissertation research on the narratives of father-absent daughters, most notably Elizabeth’s story. The author’s understanding of father-absence is situated within the multifaceted and constantly evolving discursive fields of scholarly research and personal experience. As a “vulnerable observer,” locating her own narrative within that field of stories lies at the heart of the author’s writing. This research story illustrates the ongoing challenge of creating a livable personal narrative through “a primary act of imagination.”
Found Poetry as Literature Review
Authors: Prendergast Monica
Published: February 2006

Creating found poetry from theoretical literature offers an arts-based approach to literature review in inquiry. Found poetry has a long history of practice in poetry as the imaginative appropriation and reconstruction of already-existing texts. This article presents literature-voiced research found poems that express distillations and crystallizations of a wide range of writing in contemporary continental philosophy and performance theory. The suite of poems forms part of a current dissertation inquiry in the form of a curriculum theory of audience in performance and education.
A common phosphotyrosine signature for the Bcr-Abl kinase
Authors: Goss Valerie L. , Lee Kimberly A. , Moritz Albrecht , Nardone Julie , Spek Erik J. , MacNeill Joan , Rush John , Comb Michael J. , Polakiewicz Roberto D.
Published: February 2006

The Bcr-Abl fusion kinase drives oncogenesis in chronic myeloid leukemia (CML). CML patients are currently treated with the Abl tyrosine kinase inhibitor imatinib, which is effective in early stages of the disease. However, resistance to imatinib arises in later disease stages primarily because of a Bcr-Abl mutation. To gain deeper insight into Bcr-Abl signaling pathways, we generated phosphotyrosine profiles for 6 cell lines that represent 3 Bcr-Abl fusion types by using immunoaffinity purification of tyrosine phosphopeptides followed by tandem mass spectrometry. We identified 188 nonredundant tyrosine-phosphorylated sites, 77 of which are novel. By comparing the profiles, we found a number of phosphotyrosine sites common to the 6 cell lines regardless of cellular background and fusion type, several of which are decreased by imatinib treatment. Comparison of this Bcr-Abl signature with the profile of cells expressing an alternative imatinib-sensitive fusion kinase, FIP1L1-PDGFRα, revealed that these kinases signal through different pathways. This phosphoproteomic study of the Bcr-Abl fusion kinase highlights novel disease markers and potential drug-responsive biomarkers and adds novel insight into the oncogenic signals driven by the Bcr-Abl kinase.
Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines
Authors: Che Xiao-Fang , Zheng Chun-Lei , Owatari Satsuki , Mutoh Masato , Gotanda Takenari , Jeung Hei-Cheul , Furukawa Tatsuhiko , Ikeda Ryuji , Yamamoto Masatatsu , Haraguchi Misako , Arima Naomichi , Akiyama Shin-ichi
Published: February 2006

Patients with acute- or lymphoma-type adult T-cell leukemia (ATL) have a poor outcome because of the intrinsic drug resistance to chemotherapy. Protection from apoptosis is a common feature involved in multidrug-resistance of ATL. IAP (inhibitor of apoptosis) family proteins inhibit apoptosis induced by a variety of stimuli. In this study, we investigated the expression of IAP family members (survivin, cIAP1, cIAP2, and XIAP) in the primary leukemic cells from patients with ATL. We found that survivin was overexpressed in ATL, especially in acute-type ATL. Sodium arsenite was shown to down-regulate the expression of survivin at both the protein and RNA levels in a time- and dose-dependent manner, thus inhibiting cell growth, inducing apoptosis, and enhancing the caspase-3 activity in ATL cells. Nuclear factor-κB (NF-κB) enhances the transcriptional activity of survivin. Sodium arsenite suppressed the constitutive NF-κB activation by preventing the IκB-α degradation and the nuclear translocation of NF-κB. These findings suggest that survivin is an important antiapoptotic molecule that confers drug resistance on ATL cells. Sodium arsenite was shown to down-regulate the expression of survivin through the NF-κB pathway, thus inhibiting cell growth and promoting apoptosis of ATL cells.
Identification of the angiogenic endothelial-cell growth factor-1/thymidine phosphorylase as a potential target for immunotherapy of cancer
Authors: Slager Elisabeth H. , Honders M. Willy , van der Meijden Edith D. , van Luxemburg-Heijs Simone A. P. , Kloosterboer Freke M. , Kester Michel G. D. , Jedema Inge , Marijt W. A. Erik , Schaafsma M. Ron , Willemze Roel , Falkenburg J. H. Frederik
Published: February 2006

Characterization of the antigens recognized by tumor-reactive T cells isolated from patients successfully treated with allogeneic HLA-matched hematopoietic stem cell transplantation (SCT) can lead to the identification of clinically relevant target molecules. We isolated tumor-reactive cytotoxic CD8+ T-cell (CTL) clones from a patient successfully treated with donor lymphocyte infusion for relapsed multiple myeloma after allogeneic HLA-matched SCT. Using cDNA expression cloning, the target molecule of an HLA-B7–restricted CTL clone was identified. The CTL clone recognized a minor histocompatibility antigen produced by a single nucleotide polymorphism (SNP) in the angiogenic endothelial-cell growth factor-1 (ECGF1) gene also known as thymidine phosphorylase. The SNP leads to an Arg-to-His substitution in an alternatively translated peptide that is recognized by the CTL. The ECGF1 gene is predominantly expressed in hematopoietic cells, although low expression can also be detected in other tissues. The patient from whom this CTL clone was isolated had mild graft-versus-host disease despite high numbers of circulating ECGF-1–specific T cells as detected by tetramer staining. Because solid tumors expressing ECGF-1 could also be lysed by the CTL, ECGF-1 is an interesting target for immunotherapy of both hematologic and solid tumors.
Oncogenic RAS mutations in myeloma cells selectively induce cox-2 expression, which participates in enhanced adhesion to fibronectin and chemoresistance
Authors: Hoang Bao , Zhu Li , Shi Yijiang , Frost Patrick , Yan Huajun , Sharma Sanjai , Sharma Sherven , Goodglick Lee , Dubinett Steven , Lichtenstein Alan
Published: February 2006

Oncogenic RAS expression occurs in up to 40% of multiple myeloma (MM) cases and correlates with aggressive disease. Since activated RAS induces cyclooxygenase-2 (cox-2) expression in other tumor models, we tested a role for cox-2 in mutant RAS–containing MM cells. We used the ANBL-6 isogenic MM cell lines in which the IL-6–dependent parental line becomes cytokine independent following transfection with mutated N-RAS or K-RAS. Both mutated N-RAS– and K-RAS–expressing ANBL-6 cells demonstrated a selective up-regulation of cox-2 expression and enhanced secretion of PGE2, a product of cox-2. Furthermore, in 3 primary marrow specimens, which contained MM cells expressing mutated RAS, 15% to 40% of tumor cells were positive for cox-2 expression by immunohistochemistry. We used cox-2 inhibitors, NS398 and celecoxib, and neutralizing anti-PGE2 antibody to test whether cox-2/PGE2 was involved in the aggressive phenotype of MM ANBL-6 cells containing mutated RAS. Although these interventions had no effect on IL-6–independent growth or adhesion to marrow stromal cells, they significantly inhibited the enhanced binding of mutant RAS– containing MM cells to fibronectin and the enhanced resistance to melphalan. These results indicate a selective induction of cox-2 in MM cells containing RAS mutations, which results in heightened binding to extracellular matrix protein and chemotherapeutic drug resistance.
IL-10–producing macrophages preferentially clear early apoptotic cells
Authors: Xu Wei , Roos Anja , Schlagwein Nicole , Woltman Andrea M. , Daha Mohamed R. , van Kooten Cees
Published: February 2006

Efficient clearance of apoptotic cells seems to be a prerequisite to prevent the development of autoimmunity. Here we identify that macrophage colony-stimulating factor (M-CSF)–driven macrophages (Mø2s) are potent phagocytes that have the unique capacity to preferentially bind and ingest early apoptotic cells. This macrophage subset has intrinsic anti-inflammatory properties, characterized by high interleukin-10 (IL-10) production in the absence of proinflammatory cytokines, such as IL-6 and tumor necrosis factor-α (TNF-α). Importantly, whereas the IL-6 and TNF-α production by granulocyte-macrophage (GM)–CSF–driven macrophages (Mø1s) is inhibited upon uptake of apoptotic cells, the anti-inflammatory status of Mø2 is retained during phagocytosis. Mø2s were shown to use CD14 to tether apoptotic cells, whereas recognition of phosphatidylserine (PS) contributed to uptake of early apoptotic cells. Mø2s showed more potent macropinocytosis compared with dendritic cells (DCs) and Mø1s, and uptake of apoptotic cells was inhibited by a macropinocytosis inhibitor. Our studies suggest that, under steady-state conditions, IL-10–producing Mø2s are prominently involved in the clearance of early apoptotic cells.
Endotoxin induced peritonitis elicits monocyte immigration into the lung: implications on alveolar space inflammatory responsiveness
Authors: Steinmüller Mirko , Srivastava Mrigank , Kuziel William A , Christman John W , Seeger Werner , Welte Tobias , Lohmeyer Jürgen , Maus Ulrich A
Published: February 2006

Background

Acute peritonitis developing in response to gram-negative bacterial infection is known to act as a trigger for the development of acute lung injury which is often complicated by the development of nosocomial pneumonia. We hypothesized that endotoxin-induced peritonitis provokes recruitment of monocytes into the lungs, which amplifies lung inflammatory responses to a second hit intra-alveolar challenge with endotoxin.

Methods

Serum and lavage cytokines as well as bronchoalveolar lavage fluid cells were analyzed at different time points after intraperitoneal or intratracheal application of LPS.

Results

We observed that mice challenged with intraperitoneal endotoxin developed rapidly increasing serum and bronchoalveolar lavage fluid (BALF) cytokine and chemokine levels (TNFα, MIP-2, CCL2) and a nearly two-fold expansion of the alveolar macrophage population by 96 h, but this was not associated with the development of neutrophilic alveolitis. In contrast, expansion of the alveolar macrophage pool was not observed in CCR2-deficient mice and in wild-type mice systemically pretreated with the anti-CD18 antibody GAME-46. An intentional two-fold expansion of alveolar macrophage numbers by intratracheal CCL2 following intraperitoneal endotoxin did not exacerbate the development of acute lung inflammation in response to intratracheal endotoxin compared to mice challenged only with intratracheal endotoxin.

Conclusion

These data, taken together, show that intraperitoneal endotoxin triggers a CCR2-dependent de novo recruitment of monocytes into the lungs of mice but this does not result in an accentuation of neutrophilic lung inflammation. This finding represents a previously unrecognized novel inflammatory component of lung inflammation that results from endotoxin-induced peritonitis.
Pulmonary vasoconstrictor action of KCNQ potassium channel blockers
Authors: Joshi Shreena , Balan Prabhu , Gurney Alison M
Published: February 2006

Background

KCNQ channels have been widely studied in the nervous system, heart and inner ear, where they have important physiological functions. Recent reports indicate that KCNQ channels may also be expressed in portal vein where they are suggested to influence spontaneous contractile activity. The biophysical properties of K+currents mediated by KCNQ channels resemble a current underlying the resting K+conductance and resting potential of pulmonary artery smooth muscle cells. We therefore investigated a possible role of KCNQ channels in regulating the function of pulmonary arteries by determining the ability of the selective KCNQ channel blockers, linopirdine and XE991, to promote pulmonary vasoconstriction.

Methods

The tension developed by rat and mouse intrapulmonary or mesenteric arteries was measured using small vessel myography. Contractile responses to linopirdine and XE991 were measured in intact and endothelium denuded vessels. Experiments were also carried out under conditions that prevent the contractile effects of nerve released noradrenaline or ATP, or block various Ca2+influx pathways, in order to investigate the mechanisms underlying contraction.

Results

Linopirdine and XE991 both contracted rat and mouse pulmonary arteries but had little effect on mesenteric arteries. In each case the maximum contraction was almost as large as the response to 50 mM K+. Linopirdine had an EC50of around 1 μM and XE991 was almost 10-fold more potent. Neither removal of the endothelium nor exposure to phentolamine or α,β-methylene ATP, to block α1-adrenoceptors or P2X receptors, respectively, affected the contraction. Contraction was abolished in Ca2+-free solution and in the presence of 1 μM nifedipine or 10 μM levcromakalim.

Conclusion

The KCNQ channel blockers are potent and powerful constrictors of pulmonary arteries. This action may be selective for the pulmonary circulation as mesenteric arteries showed little response. The results imply that the drugs act directly on smooth muscle cells and contraction requires voltage-dependent Ca2+influx. It is concluded that the drugs probably act by blocking KCNQ channels in pulmonary artery myocytes, leading to membrane depolarization and Ca2+influx through L-type Ca2+channels. This implies a functional role for KCNQ channels in regulating the resting membrane potential of pulmonary artery myocytes.