bluuebunny/crossref_metadata_2025 huggingface dataset:
Side Population in Human Lung Cancer Cell Lines and Tumors Is Enriched with Stem-like Cancer Cells
Authors: Ho Maria M. , Ng Alvin V. , Lam Stephen , Hung Jaclyn Y.
Published: May 2007

Stem cells have been isolated by their ability to efflux Hoechst 33342 dye and are referred to as the “side population” (SP). In this study, we used flow cytometry and Hoechst 33342 dye efflux assay to isolate and characterize SP cells from six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170). Nonobese diabetic/severe combined immunodeficiency xenograft experiments showed that SP cells were enriched in tumor-initiating capability compared with non-SP cells. Matrigel invasion assay showed that SP cells also have higher potential for invasiveness. Further characterization of this SP phenotype revealed several stem cell properties. We found evidence for repopulating ability by SP to regenerate a population resembling the original population. SP displayed elevated expression of ABCG2 as well as other ATP-binding cassette transporters and showed resistance to multiple chemotherapeutic drugs. Human telomerase reverse transcriptase expression was higher in the SP, suggesting that this fraction may represent a reservoir with unlimited proliferative potential for generating cancer cells. mRNA levels of minichromosome maintenance (MCM) 7, a member of the MCM family of proteins critical to the DNA replication complex, were lower in SP cells, suggesting that a majority of the SP fraction was in the G0 quiescent state. Sixteen clinical lung cancer samples also displayed a smaller but persistent SP population. These findings indicate that SP is an enriched source of lung tumor–initiating cells with stem cell properties and may be an important target for effective therapy and a useful tool to investigate the tumorigenic process. [Cancer Res 2007;67(10):4827–33]
Faithful Companions: A Proposal for Neurooncology Trials in Pet Dogs
Authors: Kimmelman Jonathan , Nalbantoglu Josephine
Published: May 2007

Although relatively rare, malignant glioma (MG) is frequently used for testing novel cancer treatments. However, human MG trials have often been initiated on the basis of preclinical models that involve numerous discontinuities with the human disease. Below, we discuss various limitations of the mainstay model used in MG preclinical research, the murine orthotopic xenograft. After discussing alternative model systems like transgenic mouse models and canine xenografts, we argue that companion animals with spontaneous brain cancers offer a scientifically and ethically attractive system for preclinical testing of novel MG interventions. Ethical advantages and practical challenges of companion animal brain cancer trials are briefly discussed. [Cancer Res 2007;67(10):4541–4]
Chimeric NKG2D Receptor–Bearing T Cells as Immunotherapy for Ovarian Cancer
Authors: Barber Amorette , Zhang Tong , DeMars Leslie R. , Conejo-Garcia Jose , Roby Katherine F. , Sentman Charles L.
Published: May 2007

Despite advancements in the treatment of ovarian cancer, this disease continues to be a leading cause of cancer death in women. Adoptive transfer of tumor-reactive T cells is a promising antitumor therapy for many cancers. We designed a chimeric receptor linking NKG2D, a natural killer (NK) cell–activating receptor, to the CD3ζ chain of the T-cell receptor to target ovarian tumor cells. Engagement of chimeric NKG2D receptors (chNKG2D) with ligands for NKG2D, which are commonly expressed on tumor cells, leads to T-cell secretion of proinflammatory cytokines and tumor cytotoxicity. In this study, we show that >80% of primary human ovarian cancer samples expressed ligands for NKG2D on the cell surface. The tumor samples expressed MHC class I–related protein A, MICB, and UL-16 binding proteins 1 and 3. ChNKG2D-expressing T cells lysed ovarian cancer cell lines. We show that T cells from ovarian cancer patients that express chNKG2D secreted proinflammatory cytokines when cultured with autologous tumor cells. In addition, we show that chNKG2D T cells can be used therapeutically in a murine model of ovarian cancer. These data indicate that treatment with chNKG2D-expressing T cells is a potential immunotherapy for ovarian cancer. [Cancer Res 2007;67(10):5003–8]
The Proteasome Inhibitor PS-341 (Bortezomib) Up-Regulates DR5 Expression Leading to Induction of Apoptosis and Enhancement of TRAIL-Induced Apoptosis Despite Up-Regulation of c-FLIP and Survivin Expression in Human NSCLC Cells
Authors: Liu Xiangguo , Yue Ping , Chen Shuzhen , Hu Liping , Lonial Sagar , Khuri Fadlo R. , Sun Shi-Yong
Published: May 2007

The proteasome inhibitor PS-341 (bortezomib or Velcade), an approved drug for treatment of patients with multiple myeloma, is currently being tested in clinical trials against various malignancies, including lung cancer. Preclinical studies have shown that PS-341 induces apoptosis and enhances tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis in human cancer cells with undefined mechanisms. In the present study, we show that PS-341 induced caspase-8–dependent apoptosis, cooperated with TRAIL to induce apoptosis, and up-regulated death receptor 5 (DR5) expression in human non–small cell lung cancer (NSCLC) cells. DR5 induction correlated with the ability of PS-341 to induce apoptosis. Blockage of PS-341–induced DR5 up-regulation using DR5 small interfering RNA (siRNA) rendered cells less sensitive to apoptosis induced by either PS-341 or its combination with TRAIL, indicating that DR5 up-regulation mediates PS-341–induced apoptosis and enhancement of TRAIL-induced apoptosis in human NSCLC cells. We exclude the involvement of c-FLIP and survivin in mediating these events because c-FLIP (i.e., FLIPS) and survivin protein levels were actually elevated on exposure to PS-341. Reduction of c-FLIP with c-FLIP siRNA sensitized cells to PS-341–induced apoptosis, suggesting that c-FLIP elevation protects cells from PS-341–induced apoptosis. Thus, the present study highlights the important role of DR5 up-regulation in PS-341–induced apoptosis and enhancement of TRAIL-induced apoptosis in human NSCLC cells. [Cancer Res 2007;67(10):4981–8]
Nucleophosmin Mediates Mammalian Target of Rapamycin–Dependent Actin Cytoskeleton Dynamics and Proliferation in Neurofibromin-Deficient Astrocytes
Authors: Sandsmark Danielle K. , Zhang Huabiao , Hegedus Balazs , Pelletier Corey L. , Weber Jason D. , Gutmann David H.
Published: May 2007

Neurofibromatosis type 1 (NF1) is a common autosomal dominant tumor predisposition syndrome in which affected individuals develop astrocytic brain tumors (gliomas). To determine how the NF1 gene product (neurofibromin) regulates astrocyte growth and motility relevant to glioma formation, we have used Nf1-deficient primary murine astrocytes. Nf1−/− astrocytes exhibit increased protein translation and cell proliferation, which are mediated by Ras-dependent hyperactivation of the mammalian target of rapamycin (mTOR) protein, a serine/threonine protein kinase that regulates ribosomal biogenesis, protein translation, actin cytoskeleton dynamics, and cell proliferation. In this study, we show that Nf1-deficient astrocytes have fewer actin stress fibers and exhibit increased cell motility compared with wild-type astrocytes, which are rescued by pharmacologic and genetic mTOR inhibition. We further show that mTOR-dependent regulation of actin stress fiber formation, motility, and proliferation requires rapamycin-sensitive activation of the Rac1 GTPase but not elongation factor 4E-binding protein 1/S6 kinase. Nf1−/− astrocytes also exhibit increased protein translation and ribosomal biogenesis through increased expression of the nucleophosmin (NPM) nuclear-cytoplasmic shuttling protein. We found that NPM expression in Nf1−/− astrocytes was blocked by rapamycin in vitro and in vivo and that expression of a dominant-negative NPM mutant protein in Nf1−/− astrocytes rescued actin stress fiber formation and restored cell motility and proliferation to wild-type levels. Together, these data show that neurofibromin regulates actin cytoskeleton dynamics and cell proliferation through a mTOR/Rac1-dependent signaling pathway and identify NPM as a critical mTOR effector mediating these biological properties in Nf1-deficient astrocytes. [Cancer Res 2007;67(10):4790–9]
DJ-1 Binds Androgen Receptor Directly and Mediates Its Activity in Hormonally Treated Prostate Cancer Cells
Authors: Tillman J. Erin , Yuan Jialing , Gu Guangyu , Fazli Ladan , Ghosh Ritwik , Flynt Alex S. , Gleave Martin , Rennie Paul S. , Kasper Susan
Published: May 2007

The oncogene DJ-1 has been associated with multiple cancers, including prostate cancer, where it can be stabilized by androgens and antiandrogens. However, little data exist on the expression pattern and function of DJ-1 in prostate cancer. To address the function of DJ-1 in prostate, a yeast two-hybrid screen was done to identify novel DJ-1 binding proteins. The androgen receptor (AR) was identified and confirmed as a DJ-1 binding partner. This is the first evidence that DJ-1 directly interacts with AR. We also show that modulation of DJ-1 expression regulated AR transcriptional activity. Importantly, both the subcellular localization of DJ-1 and the interaction with AR are regulated by androgens and antiandrogens. Additionally, immunohistochemical staining on two human prostate cancer tissue arrays was done providing the first large-scale expression analysis of DJ-1 in prostate. DJ-1 expression did not change with Gleason pattern but increased after androgen deprivation therapy, indicating that it may be involved in the development of androgen independence. These data provide a novel mechanism where DJ-1–mediated regulation of AR may promote the progression of prostate cancer to androgen independence. [Cancer Res 2007;67(10):4630–7]
Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo
Authors: Gu Guangyu , Yuan Jialing , Wills Marcia , Kasper Susan
Published: May 2007

Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described in terms of Gleason score, a classification not applied to any of the transgenic mouse models currently developed to mimic human disease. Immunohistochemical and Western blot analyses indicate that they do not express androgen receptor or p63, similar to that reported for prostate stem cells. These cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET cells reconstitute the original human tumor in vivo and differentiate into the three prostate epithelial cell lineages, indicating that they arise from a common stem/progenitor cell. Serial transplantation experiments reconstitute the tumors, suggesting that a fraction of parental or clonally derived HPET cells have self-renewal potential. Thus, this model may enhance our understanding of human tumor development and provide a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and the development of drug resistance. [Cancer Res 2007;67(10):4807–15]
von Hippel-Lindau: A Tumor Suppressor Links Microtubules to Ciliogenesis and Cancer Development
Authors: Kuehn E. Wolfgang , Walz Gerd , Benzing Thomas
Published: May 2007

Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic renal cell carcinoma. The tumor suppressor role of the protein pVHL is based on its ability to target transcription factors of the hypoxia-inducible factor family for degradation, but other functions of pVHL are less clearly defined. New findings show that pVHL is necessary for cilia formation. pVHL interacts with PAR proteins, a complex that specifies the membrane domains of polarized epithelial cells, and directs the orientation of growing microtubules. Loss of pVHL results in aberrant orientation of newly formed microtubules and prevents ciliogenesis. These results add to a growing body of evidence linking cilia and the cell cycle and suggest that the tumor suppressor role of pVHL may involve previously unrecognized pathways. [Cancer Res 2007;67(10):4537–40]
Phase I Trial of Weekly Paclitaxel and BMS-214662 in Patients with Advanced Solid Tumors
Authors: Bailey Howard H. , Alberti Dona B. , Thomas James P. , Mulkerin Daniel L. , Binger Kimberly A. , Gottardis Marco M. , Martell Robert E. , Wilding George
Published: May 2007

Purpose: To assess the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacodynamics, and antitumor activity of continuous weekly-administered paclitaxel and BMS-214662, a novel farnesyl transferase inhibitor.

Experimental Design: Patients were treated every week as tolerated with i.v. paclitaxel (fixed dose, 80 mg/m2/wk) administered over 1 h followed by i.v. BMS-214662 (escalating doses, 80–245 mg/m2/wk) over 1 h starting 30 min after completion of paclitaxel.

Results: Twenty-six patients received 94 courses (one course, 21 days) of study treatment. Two patients received five courses of BMS-214662 as a weekly 24-h infusion (209 mg/m2/wk). The most common toxicities were grade 1 to 2 nausea/vomiting and/or diarrhea. DLTs observed at or near the MTD (200 mg/m2/wk) were grade 4 febrile neutropenia with sepsis occurring on day 2 of course 1 (245 mg/m2/wk), reversible grade 3 to 4 serum transaminase increases on day 2, and grade 3 diarrhea (200 and 245 mg/m2/wk). Objective partial responses were observed in patients with pretreated head and neck, ovarian, and hormone-refractory prostate carcinomas, and leiomyosarcoma. The observed pharmacokinetics of paclitaxel and BMS-214662 imply no interaction between the two. Significant inhibition (>80%) of farnesyl transferase activity in peripheral mononuclear cells was observed at the end of BMS-214662 infusion.

Conclusions: Pretreated patients with advanced malignancies can tolerate weekly paclitaxel and BMS-214662 at doses that achieve objective clinical benefit. Due to multiple DLTs occurring at the expanded MTD, the recommended phase 2 dose and schedule is paclitaxel (80 mg/m2 over 1 h) and BMS-214662 (160 mg/m2 over 1 h) administered weekly.
Phase I and Pharmacokinetic Study of Vorinostat, A Histone Deacetylase Inhibitor, in Combination with Carboplatin and Paclitaxel for Advanced Solid Malignancies
Authors: Ramalingam Suresh S. , Parise Robert A. , Ramananthan Ramesh K. , Lagattuta Theodore F. , Musguire Lori A. , Stoller Ronald G. , Potter Douglas M. , Argiris Athanassios E. , Zwiebel James A. , Egorin Merrill J. , Belani Chandra P.
Published: May 2007

Purpose: The primary objective of this study was to determine the recommended phase II doses of the novel histone deacetylase inhibitor vorinostat when administered in combination with carboplatin and paclitaxel.

Experimental Design: Patients (N = 28) with advanced solid malignancies were treated with vorinostat, administered orally once daily for 2 weeks or twice daily for 1 week, every 3 weeks. Carboplatin and paclitaxel were administered i.v. once every 3 weeks. Doses of vorinostat and paclitaxel were escalated in sequential cohorts of three patients. The pharmacokinetics of vorinostat, its metabolites, and paclitaxel were characterized.

Results: Vorinostat was administered safely up to 400 mg qd or 300 mg bd with carboplatin and paclitaxel. Two of 12 patients at the 400 mg qd schedule experienced dose-limiting toxicities of grade 3 emesis and grade 4 neutropenia with fever. Non–dose-limiting toxicity included nausea, diarrhea, fatigue, neuropathy, thrombocytopenia, and anemia. Of 25 patients evaluable for response, partial responses occurred in 11 (10 non–small cell lung cancer and 1 head and neck cancer) and stable disease occurred in 7. Vorinostat pharmacokinetics were linear over the dose range studied. Vorinostat area under the concentration versus time curve and half-life increased when vorinostat was coadministered with carboplatin and paclitaxel, but vorinostat did not alter paclitaxel pharmacokinetics.

Conclusions: Both schedules of vorinostat (400 mg oral qd × 14 days or 300 mg bd × 7 days) were tolerated well in combination with carboplatin (area under the concentration versus time curve = 6 mg/mL × min) and paclitaxel (200 mg/m2). Encouraging anticancer activity was noted in patients with previously untreated non–small cell lung cancer.
CYP26 Inhibitor R115866 Increases Retinoid Signaling in Intimal Smooth Muscle Cells
Authors: Ocaya Pauline , Gidlöf Andreas C. , Olofsson Peder S. , Törmä Hans , Sirsjö Allan
Published: May 2007

Objective—Intimal smooth muscle cells (SMCs) are dedifferentiated SMCs that have a powerful ability to proliferate and migrate. This cell-type is responsible for the development of intimal hyperplasia after vascular angioplasty. Retinoids, especially all-trans retinoid acid, are known to regulate many processes activated at sites of vascular injury, including modulation of SMC phenotype and inhibition of SMC proliferation. Intracellular levels of active retinoids are under firm control. A key enzyme is the all-trans retinoic acid-degrading enzyme cytochrome p450 isoform 26 (CYP26). Thus, an alternative approach to exogenous retinoid administration could be to increase the intracellular level of all-trans retinoic acid by blocking CYP26-mediated degradation of retinoids.

Methods and Results—Vascular intimal and medial SMCs expressed CYP26A1 and B1 mRNA. Although medial cells remained unaffected, treatment with the CYP26-inhibitor R115866 significantly increased cellular levels of all-trans retinoic acid in intimal SMCs. The increased levels of all-trans retinoic acid induced retinoid-regulated genes and decreased mitogenesis.

Conclusions—Blocking of the CYP26-mediated catabolism mimics the effects of exogenously administrated active retinoids on intimal SMCs. Therefore, CYP26-inibitors offer a potential new therapeutic approach to vascular proliferative disorders.
Weight-Related Increases in Hypertension, Hypercholesterolemia, and Diabetes Risk in Normal Weight Male and Female Runners
Authors: Williams Paul T. , Hoffman Kathryn , La Isabelle
Published: May 2007

Background—

Although 36% of US men and 42% of US women are of normal weight, the health implications of greater weight in ostensibly normal-weight individuals are seldom acknowledged.

Methods and Results—

Self-reported physician-diagnosed incident diabetes, high cholesterol, and hypertension were compared with adult body mass index (BMI), and body circumferences in 29 139 male and 11 985 female nonsmoking runners followed prospectively for 7.7 and 7.4 years, respectively. Included among these were 20 731 men and 11 197 women who were of normal weight at baseline (BMI <25 kg/m
2
). During follow-up, 2342 men (8.53%) and 499 women (4.26%) became hypertensive, 3330 men (12.2%) and 599 women (5.14%) were diagnosed with high cholesterol, and 197 men (0.68%) and 28 women (0.23%) became diabetic. Increasing BMI and waist circumference at baseline significantly increased the log odds for normal-weight men becoming hypertensive (
P
<0.0001), hypercholesterolemic (
P
<0.0001), and diabetic (
P
<0.02), and for normal-weight women becoming hypertensive (
P
=0.05). The log odds for being diagnosed with high cholesterol also increased with baseline BMI in normal-weight women (
P
<0.05). Relative to men with BMI <20 kg/m
2
, the odds for being diagnosed with hypertension or high cholesterol increased by 45% (
P
=0.05) and 64% (
P
=0.002), respectively, for those with 20≤BMI<22.5 kg/m
2
, and by 121% (
P
<0.0001) and 135% (
P
<0.0001), respectively, for those with 22.5≤BMI<25 kg/m
2
. The odds for women with 22.5≤BMI<25 kg/m
2
developing hypertension or high cholesterol were 33% (
P
=0.02) and 29% (
P
=0.03) higher, respectively, than for women with 20≤BMI<22.5 kg/m
2
, and 64% (
P
=0.0007) and 41% (
P
=0.008) higher, respectively, than women with BMI <20 kg/m
2
. Relative to men and women with BMI <22.5 kg/m
2
, the odds for developing diabetes during follow-up increased by 119% (
P
=0.009) and 116% (
P
=0.17), respectively, for those with 22.5≤BMI<25 kg/m
2
.

Conclusions—

Greater BMI and larger waist circumference increase the risks for hypertension, high cholesterol, and diabetes even among normal-weight nonsmoking runners, although overall risks remain relatively low vis-a-vis those for the overweight or obese.
Direct Correlation Between Ischemic Injury and Extracellular Glycine Concentration in Mice With Genetically Altered Activities of the Glycine Cleavage Multienzyme System
Authors: Oda Masaya , Kure Shigeo , Sugawara Taku , Yamaguchi Suguru , Kojima Kanako , Shinka Toshikatsu , Sato Kenichi , Narisawa Ayumi , Aoki Yoko , Matsubara Yoichi , Omae Tomoya , Mizoi Kazuo , Kinouchi Hiroyuki
Published: May 2007

Background and Purpose—Ischemia elicits the rapid release of various amino acid neurotransmitters. A glutamate surge activatesN-methyl-d-aspartate (NMDA) glutamate receptors, triggering deleterious processes in neurons. Although glycine is a coagonist of the NMDA receptor, the effect of extracellular glycine concentration on ischemic injury remains controversial. To approach this issue, we examined ischemic injury in mice with genetically altered activities of the glycine cleavage multienzyme system (GCS), which plays a fundamental role in maintaining extracellular glycine concentration.

Methods—A mouse line with increased GCS activity (340% of C57BL/6 control mice) was generated by transgenic expression of glycine decarboxylase, a key GCS component (high-GCS mice). Another mouse line with reduced GCS activity (29% of controls) was established by transgenic expression of a dominant-negative mutant of glycine decarboxylase (low-GCS mice). We examined neuronal injury after transient occlusion of the middle cerebral artery in these mice by measuring extracellular amino acid concentrations in microdialysates.

Results—High-GCS and low-GCS mice had significantly lower and higher basal concentrations of extracellular glycine than did controls, respectively. In low-GCS mice, the extracellular glycine concentration reached 2-fold of control levels during ischemia, and infarct volume was significantly increased by 69% with respect to controls. In contrast, high-GCS mice had a significantly smaller infarct volume (by 21%). No significant difference was observed in extracellular glutamate concentrations throughout the experiments. An antagonist for the NMDA glycine site, SM-31900, attenuated infarct size, suggesting that glycine operated via the NMDA receptor.

Conclusions—There is a direct correlation between ischemic injury and extracellular glycine concentration maintained by the GCS.
Comparative Analysis of the Western Arctic Surface Climate among Observations and Model Simulations
Authors: Wu Wanli , Lynch Amanda H. , Drobot Sheldon , Maslanik James , McGuire A. David , Herzfeld Ute
Published: May 2007

Accurate estimates of the spatial and temporal variation in terrestrial water and energy fluxes and mean states are important for simulating regional hydrology and biogeochemistry in high-latitude regions. Furthermore, it is necessary to develop high-resolution hydroclimatological datasets at finer spatial resolutions than are currently available from global analyses. This study uses a regional climate model (RCM) to develop a hydroclimatological dataset for hydrologic and ecological application in the Western Arctic. The fifth-generation Penn State–NCAR Mesoscale Model (MM5) forced by global reanalysis products at the boundaries is used to perform 12 yr of simulation (1990 through 2001) over the Western Arctic. An analysis that compares the RCM simulations with independent observationally derived data sources is conducted to evaluate the temporal and spatial distribution of the mean states, variability, and trends during the period of simulation. The RCM simulation of sea level pressure agrees well with the reanalysis in terms of mean states, seasonality, and interannual variability. The RCM also simulates major spatial patterns of the observed climatology of surface air temperature (SAT), but RCM SAT is generally colder in the summertime and warmer in the wintertime in comparison with other datasets. Although there are biases in the mean state of SAT, the RCM simulations of the seasonal and interannual variability of SAT are similar to variability in observationally derived datasets. The RCM also simulates general spatial patterns of observed rainfall, but the modeled mean state of precipitation is characterized by large biases relative to observationally derived datasets. In particular, the RCM tends to overestimate coastal region precipitation but underestimates precipitation in the interior of the Western Arctic. The Arctic terrestrial surface climate trends for the period of 1992 to 2001 of the RCM are similar to those derived from observations, with sea level pressure decreasing 0.15 hPa decade−1, SAT increasing 0.10°C decade−1, and precipitation decreasing slightly in the RCM simulations. In summary, the RCM dataset produced in this study represents an improvement over data currently available from large-scale global reanalysis and provides a consistent meteorological forcing dataset for hydrologic and ecological applications.
Speaking the Same Language
Authors: Zhong Chen-Bo , Loewenstein Jeffrey , Murnighan J. Keith
Published: May 2007

The long history of experimental research on the prisoner's dilemma (PD) has primarily used a methodology that eliminates cues to participants. Researchers, however, have interpreted participants' choices as cooperative or competitive. The authors' research shows that giving participants researchers' interpretive labels of the game, the choices, and the outcomes, compared to no labels, led to significantly more cooperation; labels such as trust and cooperate/defect augmented cooperation even more. A second experiment found that independent evaluations of the labels led to perceptions that were similar to individuals' choices in the first experiment. These results suggest that we might need to rethink the import of many of our previous findings and their applicability to everyday interactions.
Hierarchy and Community at Home and Abroad
Authors: Rathbun Brian C.
Published: May 2007

Although there is increasing evidence of a relationship between domestic and foreign policy attitudes among American elites, we have less of an idea about why these sets of attitudes cohere. The answer lies in a better understanding of what we mean when we talk about “left” and “right” or “liberal” and “conservative.” Drawing on the literature on rights theory, partisan cleavages, and ideological continua, I posit the existence of two core values, hierarchy and community, that should manifest themselves both at home and abroad. I perform a principal components analysis on data capturing both the domestic and foreign policy attitudes of American elites. The results indicate an almost identical structure of attitudes in both domains, indicating that it is generally inappropriate to distinguish between the two. Using factor scores in a series of logistic regressions, I demonstrate that support for community is most important for predicting support for humanitarian military operations, while hierarchy and community both help determine positions on strategic missions.
The Challenge of Engaging Youth Online
Authors: Livingstone Sonia
Published: May 2007

Media research has long known that those who produce content and those who receive it construe textual meaning differently. Such differences may be interpreted in political, cultural, institutional and psychological terms. However, the insights from audience reception and ethnographic studies have yet fully to inform research on responses to online content. This article addresses attempts to overcome youth civic disengagement through the design and promotion of public sector, Internet-based content and services. Specifically, it integrates interviews with website producers and teenage users to compare and contrast the encoding and decoding processes in an exemplar website (www.epal.tv). An analysis in terms of genre reveals a range of communicative challenges for website producers in terms of subject matter, formal composition and mode of address. Further, critical questions arise in relation to the action consequences of online participation, interface design as this relates to teens' Internet literacy, and the power relations instantiated between producer and user. It is concluded that audience studies can constructively be extended to the analysis of Internet use and, substantively, that the policy challenge lies less in the question of whether youth is civically engaged and more in the question of who will listen to youth if and when they do become so engaged.
Understanding E-Government Benefits
Authors: Maureen Brown Mary
Published: May 2007

Past research on the topic of e-government activities is heavily rooted in describing technological innovation in terms of a maturational model. Apparently, technological innovation has occurred incrementally—and the benefits, if realized, are slow to accrue. This research examines the utility of maturational models in understanding the achievement of e-government benefits. The findings are predicated on a retrospective panel analysis of how public organizations realize the benefits of technological innovations. This study revealed that although a maturational model may be helpful for describing aggregate efforts, it is less useful in understanding the potential for individual gains. Based on the results of this sample, rapid advances, nonlinear activities, and permeable boundaries are important determinants of achieving the benefits of technological innovation and, thus, worthy of ongoing research.
Doing the Dirty Work
Authors: Duffy Mignon
Published: May 2007

The concept of reproductive labor is central to an analysis of gender inequality, including understanding the devaluation of cleaning, cooking, child care, and other “women's work” in the paid labor force. This article presents historical census data that detail transformations of paid reproductive labor during the twentieth century. Changes in the organization of cooking and cleaning tasks in the paid labor market have led to shifts in the demographics of workers engaged in these tasks. As the context for cleaning and cooking work shifted from the dominance of private household servants to include more institutional forms, the gender balance of this reproductive labor workforce has been transformed, while racial-ethnic hierarchies have remained entrenched. This article highlights the challenges to understanding occupational segregation and the devaluation of reproductive labor in a way that analyzes gender and race-ethnicity in an intersectional way and integrates cultural and structural explanations of occupational degradation.
“It's Time to Leave Machismo Behind!”
Authors: Cranford Cynthia J.
Published: May 2007

Based on an ethnography of a Latina/Latino immigrant union, the author examines changes in gender inequality along five dimensions. Union renewal weakened the structural division of union labor, allowing women on staff to realize feminist values of leadership development in concrete goals. These changes made space for women members to engage in new leadership practices that undermined gender inequalities in interactions with men and empowered and politicized women at the individual level. Feminist values of caring for children, however, were not realized in specific goals thus limiting the leadership practices and politicization of women with children. The ethnography shows the need to move from the study of women and unions to an analysis of how gendered transformations intersect with economic restructuring and immigration within social movement organizations.
Lessons from the periphery: psychiatry in Saskatchewan, Canada, 1944—68
Authors: Mills John A.
Published: May 2007

The government of the Saskatchewan Co-Operative Commonwealth Federation, when elected in 1944, established prog rammes for the state-funded care of all those suffering from mental illness. It enacted legislation covering the care and treatment of the mentally ill and created a division of the Department of Public Health, the Psychiatric Ser vices Branch (PSB), which both recr uited and trained psychiatric staff, meeting the need for non-medical staff by creating a programme for the training of psychiatric nurses in Saskatchewan. The PSB devised the Saskatchewan Plan for the deliver y of r ural services, centred on small mental hospitals of a revolutionar y design. Even though never fully instantiated, the Plan commanded worldwide attention. Saskatchewan was also remarkable for its research programmes, covering almost all aspects of psychiatry.
Changes between the 1959 and 1983 Mental Health Acts (England & Wales), with particular reference to consent to treatment for electroconvulsive therapy
Authors: Hilton Claire
Published: May 2007

Consent to treatment was not mentioned in the Mental Health Act 1959, assuming that a detained patient could be treated against his/her will. However, consent was a cr ucial new feature in the 1983 Act.This paper traces and evaluates the issues, debates, people and organizations in England and Wales who advocated and enabled this important change to come about, using examples from the clinical practice of electroconvulsive therapy.
Migration, ethnicity and competing discourses in the job interview: synthesizing the institutional and personal
Authors: Campbell Sarah , Roberts Celia
Published: May 2007

This article, based on a unique data set of video-recorded job interviews, examines the institutional and personal discourses of the competency-based interview and how their synthesis produces an `authentic self '. The interview's requirement for the synthesis of work-based and personal identities is particularly disadvantaging to foreign-born minority ethnic candidates. Foreign-born candidates often lack access to British `job interview English' because of unemployment, marginalization in ethnic work units and the dominant culture's `othering' of their identity. Examples of candidates producing a convincing synthetic persona are contrasted with unsuccessful candidates whose `lack' of synthesization marks them as having a hybrid identity. They are judged by interviewers as `inconsistent', `untrustworthy' and non-belongers to the organization. Because there is little relationship between the required discursive skill of interviewees and the actual demands of the job, the interview ritual is as much about constructing the institution as it is about the fair and effective selection of candidates.
`Black this, black that': racial insults and reported speech in neighbour complaints and police interrogations
Authors: Stokoe Elizabeth , Edwards Derek
Published: May 2007

We examine the location, design and uptake of reported racial insults and abuse across two interactional sites: telephone calls to UK neighbourhood mediation centres and police interviews with suspects in neighbourhood crimes. In the mediation data, talk about ethnicity and racism was formulated almost exclusively in `reported speech', as a listed complain-able item about neighbours rather than as the reason for the dispute. In the police data, suspects reported racial insults as counter-complaints against other parties, and police officers quoted insults reported in witness testimony as part of their interrogation. We found systematic, oriented-to practices for constructing and reporting racial insults, involving pairing national or ethnic identity categories with another word (for example, `Paki bastard', `gypsy twat', `bitch Somali'). Although speakers often `edited' insults (`nigger this', `white that'), they nevertheless maintained two-word formulations, indexing the swear-word and stating just the ethnic or national category. Speakers further oriented to the `two-wordedness' of racial insults in their carefully managed use of one-word formulations. Insults regularly contained locative phrases (for example, `fuck off back to your own country') and generalizing devices (for example, `and stuff '). Finally, we found a continuum of response types, from explicit second assessments done in ordinary talk, to minimal but aligned acknowledgements in mediation calls, to no affiliative response in police interviews. We discuss the implications of our findings for understanding the impact and relevance of racism in everyday life, as well as providing insights into the sorts of daily conflicts that occur between neighbours, as these are recounted in two institutional settings.
Frame conflict and social inequality in the workplace: professional and local discourse struggles in employee/customer interactions
Authors: Prego-Vazquez Gabriela
Published: May 2007

This article focuses on frame conflicts in workplace interactions and their role in the sociodiscursive reproduction of social inequality. Specifically, I analyse the frame conflicts that arise when customers mobilize local discursive patterns, code-switching and conversational topics. I observe how these local communicative means, which are considered to be of lesser value on the linguistic market, struggle when matched against the institutional and depersonalized discursive style of the professionals. The research is based on employee/customer interviews recorded at a partly state-owned enterprise that supplies water, sewage treatment and waste collection in a borough in Galicia (Spain). The data have been subjected to sociodiscursive, sequential and critical analyses. This multimethod aproach has enabled us to observe the way in which social order is built up from interactional order, revealing the role played by frames, linguistic resources and interactional asymmetry in reproducing the power differences that separate institutions and citizens.
Regional Cooperation in South Asia
Authors: Gonsalves Eric
Published: May 2007

Regional cooperation worldwide has not only succeeded, but also is irreversible. It is a part of globalisation, though there are limits beyond which it cannot go. So, there is a general acceptance of the present state system that disputes will not ordinarily be settled by force, that borders will not be changed, and commitment to greater integration will increase. In South Asia, regional cooperation has been a non-starter and is confined to summits and declarations. But public demand for cooperation and an expansion of contacts is growing. In response, the smaller neighbours of India do not want to open up while India itself has followed a negative policy. Relations with Bhutan and the Maldives, and now increasingly Sri Lanka, are exceptions. Even in terms of India-Pakistan relations, which are on a different plane, there are promising developments.
The Need for Economic Integration
Authors: Sobhan Rehman
Published: May 2007

South Asia inherited a shared identity, a shared infrastructure and institutions of governance, which were fractured by politics. There are now new opportunities that point to the possibility and necessity of reclaiming some of that inheritance. India's economy is now large enough to be welcomed by the various groupings in Asia as partner; while Asia is going to be, or already is, the new global growth centre. So South Asia must integrate in order to be part of this new dynamism, integrate its capital markets, its labour markets, its transport and other infrastructure, and take advantage of the new emerging opportunities for cooperation with West Asia, Southeast Asia and East Asia.
The Complexities of Border Conflicts in South Asia
Authors: Lal C.K.
Published: May 2007

In South Asia, boundaries are blurred but borders are bona fide. Boundaries have been blurred since geological time and so it has been culturally in the most recent times. Borders are of many kinds: between rival ethnic groups; between a majority and a minority; between different religious affiliations; or between citizens and denizens. Caste and class are there too, as is the difference between savage and cultured and others like the rural-urban dichotomy, all of which are prominent in South Asia. The commons—air, water, land—give rise to claim and counter-claim; and the political borders defy reason. It is, finally, in the mind of man that the geo-cultural unity of South Asia has to be constructed.
Cooperation with Realism
Authors: Baral Lok Raj
Published: May 2007

South Asian cooperation continues to stagnate, in contrast to other regions. In terms of economic cooperation, information flows, value systems and ideas of security the differences are more in evidence than the similarities, and it is the political gulf that needs to be bridged. The spirit of regional cooperation has to be developed through a conceptual vision of a new region. But enlargement is not likely to be of help. The reconstruction of the South Asian state is the prime need of the region. Democracy has to be genuinely participatory; the intra-state regional balance is an essential component of this; and the structure and functions of government need to be addressed. South Asian states have to find a common roadmap leading to cooperation and friendship. For each state the legitimacy of power is the paramount guide in this regard.
Gas Export by Pipeline from Iran to the Indian Subcontinent
Authors: Ghorban Narsi
Published: May 2007

There are huge reserves of gas in India's neighbouring region, about 42 per cent of the world's total. Gas is a fuel of advantage with a large demand in India. In Iran, one group believes gas should be exported while the other believes that gas should be used only for Iran's own needs. Alternative routes for the gas export pipeline have been studied in the past but government involvement has always led to delays. Now, however, rapid economic growth in India has led to an increased need for energy. Regional companies are increasingly capable so that there is no need to look outside the region for a task like this, and a lot of funds are available in the Gulf waiting to be invested in a project like this. Proper laws and regulations have to be adopted, and innovative financing will be needed. The pipeline will bring economic integration, will create jobs and promote trust between India and Pakistan.
Concept and Function of the ACMECS
Authors: Sucharithanarugse Withaya
Published: May 2007

The end of the Cold War facilitated the expansion of the Association of Southeast Asian Nations (ASEAN) to include Cambodia, Laos, Myanmar and Vietnam (CLMV), all with lower economic standards than the original six members. Within this expanded framework, sub-regions have been formed, among them the Greater Mekong Sub-region (GMS), followed by a Cambodia-Laos-Vietnam Development Triangle and now by the Ayeyawadi-Chao Praya-Mekong Economic Cooperation Strategy (ACMECS). The latter was initiated by Thai Premier Thaksin Shinawatra. The Bagan declaration of 2003 sets out its aims. External partners are there and now this forum resembles a mini-ASEAN, with the detailed programmes and schedules of meetings that it has. But the promotion of ACMECS also enriches Thaksin's business empire, while there is some hint here of Sino-Japanese rivalry. In a globalised world, ACMECS cannot afford to be a closed group and it will not be long before India is invited to join.
Reorienting the Regional discourse on South Asia
Authors: Tripathi Rahul
Published: May 2007

The recent discourse on regionalism in South Asia has been marked more with the problems that hinder regional cooperation rather than the prospects that the grouping has in shaping the collective future of the region. Given the faltering steps the South Asian Association for Regional Cooperation (SAARC) has taken at regionalism in the last two decades, such pessimism is perhaps justified. As an institution, SAARC has remained an intergovernmental mechanism, which has had little relevance for the people of South Asia. The association has allowed the political logic to dominate over the economic, and therefore lags far behind several other regional and multilateral initiatives. The article revisits the existing regional discourse in South Asia and offers an alternative approach to the regional idea, the thrust for which comes from people below rather than the states at the top. According to this alternative paradigm, states must merely act as facilitators rather than initiators of regional initiatives and build upon evolving interactions in South Asia based on knowledge, technology, commerce and culture. This would require a reinterpretation of the operative mechanism of SAARC by modifying its original mandate and procedures. Secondly it would need greater accommodation and acceptance of each other's concerns by all South Asian countries and an approach that looks beyond the traditional notions of dominance and dependence.
Regional Cooperation for Human Security
Authors: Mohsin Amena
Published: May 2007

This article examines briefly the major stumbling blocks in the progress of the South Asian Association for Regional Cooperation (SAARC) as a regional grouping, and then goes on to focus on three contentious issues that persist between India and Bangladesh, each of them with implications for human security. The first is ethnic divides and trans-border insurgencies, in which India is a factor. The second is the water issue between India and Bangladesh, not just arising from Farakka, but also from the Tipaimukh hydroelectric project in Assam. The third concerns the border and includes questions of trafficking in women and drugs and arms. It concludes that the region has to get out of the trap by cultivating a South Asian mind.
Youth Audience Segmentation Strategies for Smoking-Prevention Mass Media Campaigns Based on Message Appeal
Authors: Flynn Brian S. , Worden John K. , Bunn Janice Yanushka , Dorwaldt Anne L. , Connolly Scott W. , Ashikaga Takamaru
Published: May 2007

Mass media interventions are among the strategies recommended for youth cigarette smoking prevention, but little is known about optimal methods for reaching diverse youth audiences. Grades 4 through 12 samples of youth from four states ( n = 1,230) rated smoking-prevention messages in classroom settings. Similar proportions of African American, Hispanic, and White youth participated. Impact of audience characteristics on message appeal ratings was assessed to provide guidance for audience segmentation strategies. Age had a strong effect on individual message appeal. The effect of gender also was significant. Message ratings were similar among the younger racial/ethnic groups, but differences were found for older African American youth. Lower academic achievement was associated with lower appeal scores for some messages. Age should be a primary consideration in developing and delivering smoking-prevention messages to youth audiences. The unique needs of boys and girls and older African American adolescents should also be considered.
Appropriations: Dynamics of Domestic Space Negotiations in Italian Middle-Class Working Families
Authors: Giorgi Sabina , Padiglione Vincenzo , Pontecorvo Clotilde
Published: May 2007

This article concerns the dynamics of domestic space `appropriation' in Italian middle-class working families. The article starts from a background in multidisciplinary literature, mostly in the area of ethnographical and psychological studies, where the concepts of both `ownership' and `territoriality' prove to be inadequate. A dynamic view of space appropriations is chosen instead: starting from `outside appropriations', the presence of marked thresholds is then considered. Secondly, domestic space appropriations within the house are analysed in a purely qualitative way. There are selective and `predominant' appropriations by a single family member and by the whole household; questions of sovereignty and painful `proscriptions' (kingdoms and exiles) arise when specific parts of the house pertain to a given individual. But there are also unstable appropriations which reveal that there are negotiations in progress according to the family's power dynamics. Thus defined, the categories of domestic space also provide a key to understanding the families' relationships.